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1. Impact of cirrhosis aetiology on incidence and prognosis of hepatocellular carcinoma diagnosed during surveillance

Author: Nathalie Ganne-Carrié, Pierre Nahon, Cendrine Chaffaut, Gisèle N’Kontchou, Richard Layese, Etienne Audureau, Sylvie Chevret, Isabelle Archambeaud, Louis d’Alteroche, Frédéric Oberti, Dominique Roulot, Christophe Moreno, Alexandre Louvet, Thông Dao, Romain Moirand, Odile Goria, Eric Nguyen-Khac, Nicolas Carbonell, Jean-Charles Duclos-Vallée, Stanislas Pol, Victor de Ledinghen, Violaine Ozenne, Jean Henrion, Jean-Marie Péron, Albert Tran, Gabriel Perlemuter, Xavier Amiot, Jean-Pierre Zarski, Tarik Asselah, Dominique Guyader, Hélène Fontaine, Georges-Philippe Pageaux, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Jean-Pierre Bronowicki, Thomas Decaens, Ghassan Riachi, Paul Calès, Laurent Alric, Marc Bourlière, Philippe Mathurin, Sebastien Dharancy, Jean-Frédéric Blanc, Armand Abergel, Olivier Chazouillères, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Claire Wartelle, Dominique Thabut, Christophe Pilette, Christine Silvain, Christos Christidis, Brigitte Bernard-Chabert, Sophie Hillaire, and Vincent Di Martino
Subjects: alcoholic liver disease, cirrhosis, primary liver cancer, competing risk analysis, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: In this study we aimed to analyse the impact of the aetiology of cirrhosis on the incidence, characteristics and prognosis of hepatocellular carcinoma (HCC) diagnosed during a surveillance program. Methods: Individual data from a randomized trial and 2 prospective cohorts of patients with compensated histologically proven cirrhosis recruited between 2000 and 2016 were pooled. The influence of cirrhosis aetiology on survival after HCC detection was assessed using multivariable regression models. Results: Among 3,533 patients (1,926 virus [VIR], 1,167 alcohol [ALC], 440 combined [MIX]), 431 were diagnosed with HCC after a median follow-up of 57.1 months. The 5-year HCC incidence was lowest in ALC (VIR 12.6%, ALC 9.1%, MIX 14.3%, p = 0.04). At the time of diagnosis, tumour burden and Child-Pugh score were comparable across aetiology groups, but early BCLC stages (0/A) were significantly less frequent in ALC (VIR 80%, ALC 37%, MIX 72%) as a result of worse ECOG performance status. However, similar access to first-line curative HCC treatment was reported across aetiology groups (p = 0.68). Median survival after HCC diagnosis was significantly reduced in ALC (VIR 39, ALC 21, MIX 34 months, p = 0.02). However, when adjusting for tumour size, ECOG and Child-Pugh score, the aetiology of the underlying cirrhosis no longer had a significant impact. Conclusion: Compared to patients with virus-related cirrhosis, patients with alcohol-related compensated cirrhosis enrolled in a surveillance program have: i) the lowest 5-year HCC incidence; ii) worse overall prognosis, mostly driven by a poor general condition, despite similar access to first-line curative treatment. Lay summary: It has been suggested that early detection of hepatocellular carcinoma (HCC) may be futile in patients with alcohol-related cirrhosis. By comparing outcomes in more than 3,000 patients with compensated cirrhosis included in surveillance programs, this study suggests that HCC surveillance enables early diagnosis in most patients with alcohol-related cirrhosis despite a higher competing risk of death in these patients. We also report similar access to first-line curative HCC treatment in these patients compared to those with viral cirrhosis, despite higher rates of comorbidities and impaired liver function. Following HCC detection, the later parameters were major drivers of death irrespective of the cause of cirrhosis. Registration: CHC2000 (NCT00190385) and CIRRAL (NCT01213927) cohorts were registered at ClinicalTrials.gov and the full protocols are available at the following links (https://clinicaltrials.gov/ct2/show/NCT00190385) and https://clinicaltrials.gov/ct2/show/NCT01213927, respectively). The full CirVir protocol is available via the ANRS Web site (http://anrs.fr).
Published: 2021
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2. Safety and efficacy of the combination simeprevir-sofosbuvir in HCV genotype 1- and 4-mono-infected patients from the French ANRS CO22 hepather cohort

Author: Anne Laurain, Sophie Metivier, Georges Haour, Dominique Larrey, Céline Dorival, Christophe Hezode, Fabien Zoulim, Patrick Marcellin, Marc Bourliere, Jean-Pierre Zarski, Dominique Thabut, Laurent Alric, Nathalie Ganne-Carrie, Paul Cales, Jean-Pierre Bronowicki, Ghassan Riachi, Claire Geist, Xavier Causse, Armand Abergel, Olivier Chazouilleres, Philippe Mathurin, Dominique Guyader, Didier Samuel, Albert Tran, Véronique Loustaud-Ratti, Ventzislava Petrov-Sanchez, Alpha Diallo, Clovis Luzivika-Nzinga, Hélène Fontaine, Fabrice Carrat, Stanislas Pol, and on behalf of the ANRS/AFEF HEPATHER study group
Subjects: Direct acting antivirals, Hepatitis C virus, Real life cohort, Simeprevir, Sofosbuvir, Infectious and parasitic diseases, RC109-216
Abstract: Abstract Background Although real-life results of sofosbuvir/simeprevir have been extensively reported from the United States, data from other geographical areas are limited. In the French observational cohort, ANRS CO22 HEPATHER, 9432 patients were given the new oral antivirals from December 2013 to June 30, 2018. We report the results of sofosbuvir/simeprevir in genotypes 1- and 4-infected patients. Methods Demographics and history of liver disease were collected at entry in the cohort. Clinical, adverse events, and virological data were collected throughout treatment and post-treatment follow-up. The choice of treatment duration or addition of ribavirin was left up to the physician. Results Five hundred ninety-nine HCV (467 genotype 1 and 132 genotype 4) mono-infected, naïve for all oral-DAAs regimen patients were given sofosbuvir/simeprevir with (n = 63) or without ribavirin (n = 536) for 12 or 24 weeks; 56% had cirrhosis (4% decompensated) and 71% had prior treatment failure to interferon-based regimen. 7 patients (1.16%) were lost to follow-up. The overall SVR12 rate was 92.6%. The SVR12 was 90% in GT1a, 94.2% in GT1b and 91.6% in GT4 with no significant difference for genotype, treatment duration or ribavirin addition. Severity of liver disease was not associated with a lower SVR12 rate on multivariate analysis but was associated with a higher rate of severe side effects. Early treatment discontinuations were rare; no new safety signals were reported. Conclusion In this real life, observational, prospective cohort study, the 12-week sofosbuvir/simeprevir+/−ribavirin combination appears to be efficient and safe. Trial registration Trial registration with ClinicalTrials.gov NCT01953458.
Published: 2019
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3. Integrating genetic variants into clinical models for hepatocellular carcinoma risk stratification in cirrhosis

Author: Pierre Nahon, Jessica Bamba-Funck, Richard Layese, Eric Trépo, Jessica Zucman-Rossi, Carole Cagnot, Nathalie Ganne-Carrié, Cendrine Chaffaut, Erwan Guyot, Marianne Ziol, Angela Sutton, Etienne Audureau, Tarik Asselah, Dominique Guyader, Stanislas Pol, Hélène Fontaine, Georges-Philippe Pageaux, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Thomas Decaensi, Ghassan Riachi, Paul Calès, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, Sebastien Dharancy, Jean-Frédéric Blanc, Armand Abergel, Olivier Chazouillères, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, null Louis d’Alteroche, Claire Wartelle, Thông Dao, Dominique Thabut, Christophe Pilette, Christine Silvain, Christos Christidis, Eric Nguyen-Khac, Brigitte Bernard-Chabert, Sophie Hillaire, Vincent Di Martino, Isabelle Archambeaud, Louis d’Alteroche, Frédéric Oberti, Christophe Moreno, Alexandre Louvet, Romain Moirand, Odile Goria, Nicolas Carbonell, Jean-Charles Duclos-Vallée, Victor de Ledinghen, Violaine Ozenne, Jean Henrion, Gabriel Perlemuter, Xavier Amiot, Jean-Pierre Zarski, and Sylvie Chevret
Subjects: Hepatology
Abstract: This study aimed to evaluate the ability of single nucleotide polymorphisms (SNPs) to refine hepatocellular carcinoma (HCC) risk stratification.Six SNPs in PNPLA3, TM6SF2, HSD17B13, APOE, and MBOAT7 affecting lipid turnover and one variant involved in the Wnt-β-catenin pathway (WNT3A-WNT9A rs708113) were assessed in patients with alcohol-related and/or HCV-cured cirrhosis included in HCC surveillance programs (prospective CirVir and CIRRAL cohorts). Their prognostic value for HCC occurrence was assessed using Fine-Gray models combined into a 7-SNP genetic risk score (GRS). Prediction ability of two clinical scores (a routine nongenetic model determined by multivariate analysis and the external aMAP score) without then with the addition of the GRS was evaluated by C-indices. The standardized net benefit was derived from decision curves.Among 1145 patients, 86 (7.5%) developed HCC after 43.7 months. PNPLA3 and WNT3A-WNT9A variants were independently associated with HCC occurrence. The GRS stratified the population into 3 groups with progressively increased 5-yr HCC incidence [Group 1 (n=627, 5.4%), Group 2 (n=276, 10.7%), and Group 3 (n=242, 15.3%); P0.001]. The multivariate model identified age, male sex, diabetes, platelet count, GGT levels, albuminemia and the GRS as independent risk factors. The clinical model performance for 5-yr HCC prediction was similar to that of the aMAP score (C-Index 0.769). The addition of the GRS to both scores modestly improved their performance (C-Index 0.786 and 0.783, respectively). This finding was confirmed by decision curve analyses showing only fair clinical net benefit.Patients with cirrhosis can be stratified into HCC risk classes by variants affecting lipid turnover and Wnt-β-catenin pathway. The incorporation of this genetic information modestly improves the performance of clinical scores.The identification of patients at higher probability of developing liver cancer is pivotal to improve the performance of surveillance. Risk assessment can be achieved by combining several clinical and biological parameters used in routine practice. The addition of patients' genetic characteristics can modestly improve this prediction and will ultimately pave the way for precision medicine in patients eligible for HCC surveillance, allowing physicians to trigger personalized screening strategies.
Published: 2023

4. Increased Intrahepatic Expression of Immune Checkpoint Molecules in Autoimmune Liver Disease

Author: Zuzana Macek Jilkova, Marie Noelle Hilleret, Theophile Gerster, Nathalie Sturm, Marion Mercey-Ressejac, Jean-Pierre Zarski, Vincent Leroy, Patrice N. Marche, Charlotte Costentin, and Thomas Decaens
Subjects: autoimmune liver disease, autoimmune hepatitis, immune checkpoint molecules, PD-1, 4-1BB, Cytology, QH573-671
Abstract: Immune checkpoint molecules (ICM) are critical in maintaining immunologic homeostasis and participate in preventing or promoting autoimmune disease development. Exploring a large panel of intrahepatic inhibitory and stimulatory ICM is necessary for drawing a general picture of the immune alterations in autoimmune hepatitis (AIH). Here, we performed a multiparametric analysis of ICM, including PD-1, TIM3, LAG3, CTLA-4, OX40 and 4-1BB, and we determined their expression on intrahepatic lymphocyte subsets in untreated and in treated patients with AIH in comparison to normal liver tissue. AIH patient-derived liver tissue revealed the overexpression of ICM, mainly PD-1 and 4-1BB, as well as the strong correlation between PD-1+ CD8+ T-cell abundance and severity of AIH (alanine transaminase and aspartate transaminase levels). Our results show that the ICM play an important role in the loss of immune homeostasis in the liver, providing an attractive approach to investigate their role as targets for effective therapeutic interventions.
Published: 2021
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5. Mass Spectrometry-Based Proteomics Reveal Alcohol Dehydrogenase 1B as a Blood Biomarker Candidate to Monitor Acetaminophen-Induced Liver Injury

Author: Floriane Pailleux, Pauline Maes, Michel Jaquinod, Justine Barthelon, Marion Darnaud, Claire Lacoste, Yves Vandenbrouck, Benoît Gilquin, Mathilde Louwagie, Anne-Marie Hesse, Alexandra Kraut, Jérôme Garin, Vincent Leroy, Jean-Pierre Zarski, Christophe Bruley, Yohann Couté, Didier Samuel, Philippe Ichai, Jamila Faivre, and Virginie Brun
Subjects: bioinformatics, proteomics, mass spectrometry, liver, blood, biomarker, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Acute liver injury (ALI) is a severe disorder resulting from excessive hepatocyte cell death, and frequently caused by acetaminophen intoxication. Clinical management of ALI progression is hampered by the dearth of blood biomarkers available. In this study, a bioinformatics workflow was developed to screen omics databases and identify potential biomarkers for hepatocyte cell death. Then, discovery proteomics was harnessed to select from among these candidates those that were specifically detected in the blood of acetaminophen-induced ALI patients. Among these candidates, the isoenzyme alcohol dehydrogenase 1B (ADH1B) was massively leaked into the blood. To evaluate ADH1B, we developed a targeted proteomics assay and quantified ADH1B in serum samples collected at different times from 17 patients admitted for acetaminophen-induced ALI. Serum ADH1B concentrations increased markedly during the acute phase of the disease, and dropped to undetectable levels during recovery. In contrast to alanine aminotransferase activity, the rapid drop in circulating ADH1B concentrations was followed by an improvement in the international normalized ratio (INR) within 10–48 h, and was associated with favorable outcomes. In conclusion, the combination of omics data exploration and proteomics revealed ADH1B as a new blood biomarker candidate that could be useful for the monitoring of acetaminophen-induced ALI.
Published: 2021
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6. Low alcohol consumption influences outcomes in individuals with alcohol-related compensated cirrhosis in a French multicenter cohort

Author: Alexandre Louvet, Valérie Bourcier, Isabelle Archambeaud, Louis d’Alteroche, Cendrine Chaffaut, Frédéric Oberti, Christophe Moreno, Dominique Roulot, Thông Dao, Romain Moirand, Jean-Charles Duclos-Vallée, Odile Goria, Eric Nguyen-Khac, Stanislas Pol, Nicolas Carbonell, Jérôme Gournay, Laure Elkrief, Isabelle Fouchard-Hubert, Sylvie Chevret, Nathalie Ganne-Carrié, null Louis d’Alteroche, Jean-Marie Péron, Victor de Lédinghen, Violaine Ozenne, Jean Henrion, Albert Tran, Gabriel Perlemuter, Xavier Amiot, Jean-Pierre Zarski, CHU Lille, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Erasme [Bruxelles], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Pontchaillou [Rennes], Hôpital Paul Brousse, Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Amiens-Picardie, Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 (GRAP), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Département d'hépatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CIRRAL group, École pratique des hautes études (EPHE), CHU Trousseau [Tours], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Référence des Maladies Rares - Maladies Inflammatoires des Voies Biliaires et Service d’Hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), and Hopital Saint-Louis [AP-HP] (AP-HP)
Subjects: liver decompensation, [PHYS]Physics [physics], Alcohol-related liver disease, Cirrhosis, Hepatology, Recurrence, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background and aims: The harmful impact of heavy alcohol recurrence has been confirmed in patients with alcohol-related cirrhosis although this is based on old studies. The drivers of long-term outcome still need to be clearly investigated.Method: All patients with biopsy-proven compensated alcohol-related cirrhosis included in the CIRRAL cohort (22 centers) were prospectively studied. Prognostic variables of survival and liver event-free survival were assessed using multivariable Cox models with stepwise selection. The prognostic impact of alcohol recurrence during follow-up (computed in glasses-years in the same way as pack-years for tobacco) was assessed using a time-dependent covariable.Results: From 2010 to 2016, 650 patients were included. The median age at baseline was 58.4 years old, 67.4% were men and the median BMI was 27.8 kg/m2, 63.8% had a history of liver decompensation, and 70.2% had discontinued alcohol. At 5 years, 30.9% of abstinent patients developed recurrence and this risk was higher in patients with a history of drug abuse and in those with shorter alcohol discontinuation times. Median survival was 97 months. Age, alcohol consumption at baseline, platelet count and Child-Pugh score >5 were associated with overall and liver event-free survival on multivariate analysis. Alcohol consumption during follow-up of more than 25 glasses-year was independently associated with lower survival and with a trend toward significant liver event-free survival, but the risk increased from 1 glass-year, though not significantly. Simon & Makuch plots confirm the benefit of no alcohol consumption (
Published: 2022

7. EASL‐ALEH 2015 algorithm for the use of transient elastography in treatment‐naive patients with hepatitis B: An independent validation

Author: Tarik Asselah, Jean Nana, Jean-Pierre Zarski, Nathalie Sturm, Vincent Leroy, Michael Adler, Jean Luc Bosson, and Kristina Skaare
Subjects: Liver Cirrhosis, Biopsy, Liver fibrosis, Population, Therapy naive, 03 medical and health sciences, Hepatitis B, Chronic, 0302 clinical medicine, Virology, medicine, Humans, 030212 general & internal medicine, education, Retrospective Studies, education.field_of_study, Hepatology, medicine.diagnostic_test, business.industry, Fibrosis stage, Hepatitis B, medicine.disease, Confidence interval, Infectious Diseases, Liver, Liver biopsy, Elasticity Imaging Techniques, 030211 gastroenterology & hepatology, business, Transient elastography, Algorithm, Algorithms
Abstract: Various non-invasive methods have been evaluated in chronic hepatitis B, but none of them have been fully validated for the assessment of liver fibrosis. The issued EASL-ALEH 2015 guidelines provide detailed algorithms based on LSM and ALT serum levels. The aim of our study was to validate the diagnostic accuracy of this algorithm and to better understand discrepancies. Four hundred and thirteen patients from 3 centres were retrospectively included. All included patients were classified for fibrosis stage according to results of a liver biopsy. The overall diagnostic value was expressed with AUROCs given with 95% confidence intervals for the diagnostic targets. For each diagnostic target, optimal cut-offs were determined according to the Youden method. For the population of patients with ALTN (n = 65), the AUROCs of TE were 0.75 (0.62-0.88) and 0.72 (0.56-0.88) for F ≥ 2 and F ≥ 3 diagnostic targets. Taking the EASL cut-offs, the prevalence of significant fibrosis was 8%, 38% and 67% when LSM was6kPa, between 6 and 9 kPa or9 kPa, respectively. For patients with ALTN but ≤5N (n = 306), AUROCs of transient elastography were 0.79 (0.73-0.84) and 0.84 (0.75-0.92) for F ≥ 2 and F ≥ 3 diagnostic targets. The prevalence of significant fibrosis was, respectively, 15%, 52% and 85% when LSM was6kPa, between 6 and 12 kPa or12 kPa. Our study independently validates the EASL-ALEH algorithm based on ALT levels and LSM assessed by transient elastography.
Published: 2021

8. Interactions between Hepatitis C Virus and the Human Apolipoprotein H Acute Phase Protein: A Tool for a Sensitive Detection of the Virus.

Author: Ilias Stefas, Sylvia Tigrett, Grégor Dubois, Marco Kaiser, Estelle Lucarz, Delphine Gobby, Dorothy Bray, Heinz Ellerbrok, Jean Pierre Zarski, and Francisco Veas
Subjects: Medicine, Science
Abstract: The Hepatitis C virus (HCV) infection exhibits a high global prevalence frequently associated with hepatocellular carcinoma, taking years to develop. Despite the standardization of highly sensitive HCV quantitative RT-PCR (qRT-PCR) detection methods, false-negative diagnoses may be generated with current methods, mainly due to the presence of PCR inhibitors and/or low viral loads in the patient's sample. These false-negative diagnoses impact both public health systems, in developing countries, and an in lesser extent, in developed countries, including both the risk of virus transmission during organ transplantation and/or blood transfusion and the quality of the antiviral treatment monitoring. To adopt an appropriate therapeutic strategy to improve the patient's prognosis, it is urgent to increase the HCV detection sensitivity. Based upon previous studies on HBV, we worked on the capacity of the scavenger acute phase protein, Apolipoprotein H (ApoH) to interact with HCV. Using different approaches, including immunoassays, antibody-inhibition, oxidation, ultracentrifugation, electron microscopy and RT-PCR analyses, we demonstrated specific interactions between HCV particles and ApoH. Moreover, when using a two-step HCV detection process, including capture of HCV by ApoH-coated nanomagnetic beads and a home-made real-time HCV-RT-PCR, we confirmed the presence of HCV for all samples from a clinical collection of HCV-seropositive patients exhibiting an RT-PCR COBAS® TaqMan® HCV Test, v2.0 (COBAS)-positive result. In contrast, for HCV-seropositive patients with either low HCV-load as determined with COBAS or exhibiting HCV-negative COBAS results, the addition of the two-step ApoH-HCV-capture and HCV-detection process was able to increase the sensitivity of HCV detection or more interestingly, detect in a genotype sequence-independent manner, a high-proportion (44%) of HCV/RNA-positive among the COBAS HCV-negative patients. Thus, the immune interaction between ApoH and HCV could be used as a sample preparation tool to enrich and/or cleanse HCV patient's samples to enhance the detection sensitivity of HCV and therefore significantly reduce the numbers of false-negative HCV diagnosis results.
Published: 2015
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9. Functions of liver natural killer cells are dependent on the severity of liver inflammation and fibrosis in chronic hepatitis C.

Author: Emilie Fugier, Hélène Marche, Marie-Ange Thélu, Zuzana Macek Jílková, Nicolas Van Campenhout, Tania Dufeu-Duchesne, Vincent Leroy, Jean-Pierre Zarski, Nathalie Sturm, Patrice N Marche, and Evelyne Jouvin-Marche
Subjects: Medicine, Science
Abstract: During chronic hepatitis C virus (HCV) infection, the role of intra-hepatic (IH) natural killer (NK) cells is still controversial. To clarify their functions, we investigated anti-viral and cytotoxic activity of NK cells in human fresh liver biopsies. We compared the functions of IH-NK cells in HCV-infected and NASH patients in physiological conditions as well as after stimulation using flow cytometric and immunohistochemical analyses. Interestingly, few IH-NK cells produced anti-viral cytokine IFN-γ in HCV-infected patients similarly as in non-infected individuals. Spontaneous degranulation activity was extremely low in peripheral NK cells compared to IH-NK cells, and was significantly higher in IH-NK cells from HCV-infected patients compared to non-infected individuals. Immunohistochemical analysis revealed that perforin granules were polarized at the apical pole of IH-NK cells. The presence of CD107a and perforin in IH-NK cells demonstrated that NK cells exerted a cytolytic activity at the site of infection. Importantly, IH-NK cell functions from HCV-infected patients were inducible by specific exogenous stimulations. Upon ex vivo K562 target cell stimulations, the number of degranulating NK cells was significantly increased in the pool of IH-NK cells compared to circulating NK cells. Interestingly, after stimulation, the frequency of IFN-γ-producing IH-NK cells in HCV-infected patients was significantly higher at early stage of inflammation whereas the spontaneous IH-NK cell degranulation activity was significantly impaired in patients with highest inflammation and fibrosis Metavir scores. Our study highlights that some IH-NK cells in HCV-infected patients are able to produce INF-γ and degranulate and that those two activities depend on liver environment including the severity of liver injury. Thus, we conclude that critical roles of IH-NK cells have to be taken into account in the course of the liver pathogenesis associated to chronic HCV infection.
Published: 2014
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10. Including Ratio of Platelets to Liver Stiffness Improves Accuracy of Screening for Esophageal Varices That Require Treatment

Author: Arthur Berger, Federico Ravaioli, Oana Farcau, Davide Festi, Horia Stefanescu, François Buisson, Pierre Nahon, Christophe Bureau, Nathalie Ganne-Carriè, Annalisa Berzigotti, Victor de Ledinghen, Salvatore Petta, Paul Calès, Sylvie Sacher Huvelin, Dominique Valla, Anne Olivier, Frédéric Oberti, Jérôme Boursier, Jean Paul Galmiche, Jean Pierre Vinel, Clotilde Duburque, Alain Attar, Isabelle Archambeaud, Robert Benamouzig, Marianne Gaudric, Dominique Luet, Patrice Couzigou, Lucie Planche, Emmanuel Coron, Jean-Baptiste Hiriart, Faiza Chermak, Maude Charbonnier, Patrick Marcellin, Dominique Guyader, Stanislas Pol, Hélène Fontaine, Dominique Larrey, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Jean-Pierre Zarski, Vincent Leroy, Ghassan Riachi, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, Sebastien Dharancy, Jean-Frédéric Blanc, Armand Abergel, Lawrence Serfaty, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Yannick Bacq, Claire Wartelle, Thông Dao, Yves Benhamou, Christophe Pilette, Christine Silvain, Christos Christidis, Dominique Capron, Gérard Thiefin, Sophie Hillaire, Vincent Di Martino, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Regional Institute of Gastroenterology and Hepatology [Cluj-Napoca], Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université Paris 13 (UP13), Hôpital Cochin [AP-HP], Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Institutional support was provided by Programme hospitalier de recherche Clinique and agence nationale de recherches sur le sida et les hépatites virales, who had no other role in the present study., École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), Berger A., Ravaioli F., Farcau O., Festi D., Stefanescu H., Buisson F., Nahon P., Bureau C., Ganne-Carrie N., Berzigotti A., de Ledinghen V., Petta S., Cales P., Huvelin S.S., Valla D., Olivier A., Oberti F., Boursier J., Galmiche J.P., Vinel J.P., Duburque C., Attar A., Archambeaud I., Benamouzig R., Gaudric M., Luet D., Couzigou P., Planche L., Coron E., Hiriart J.-B., Chermak F., Charbonnier M., Marcellin P., Guyader D., Pol S., Fontaine H., Larrey D., De Ledinghen V., Ouzan D., Zoulim F., Roulot D., Tran A., Bronowicki J.-P., Zarski J.-P., Leroy V., Riachi G., Peron J.-M., Alric L., Bourliere M., Mathurin P., Dharancy S., Blanc J.-F., Abergel A., Serfaty L., Mallat A., Grange J.-D., Attali P., Bacq Y., Wartelle C., Dao T., Benhamou Y., Pilette C., Silvain C., Christidis C., Capron D., Thiefin G., Hillaire S., and Di Martino V.
Subjects: Blood Platelets, Liver Cirrhosis, Noninvasive Diagnosis, medicine.medical_specialty, Cirrhosis, [SDV]Life Sciences [q-bio], Population, Esophageal and Gastric Varices, Chronic liver disease, Severity of Illness Index, Gastroenterology, End Stage Liver Disease, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Model for End-Stage Liver Disease, Esophageal varices, Internal medicine, Nonalcoholic fatty liver disease, medicine, Humans, education, Baveno VI Criteria, Retrospective Studies, education.field_of_study, Hepatology, business.industry, Retrospective cohort study, Portal Hypertension, medicine.disease, 3. Good health, MELD, 030220 oncology & carcinogenesis, Elasticity Imaging Techniques, 030211 gastroenterology & hepatology, business, Baveno VI Criteria, Blood Platelets, Cirrhosis, Elasticity Imaging Techniques, End Stage Liver Disease, Esophageal and Gastric Varices, Humans, Liver Cirrhosis, MELD, Noninvasive Diagnosis, Portal Hypertension, Retrospective Studies, Severity of Illness, Index
Abstract: International audience; Background & aims: Based on platelets and liver stiffness measurements, the Baveno VI criteria (B6C), the expanded B6C (EB6C), and the ANTICIPATE score can be used to rule out varices needing treatment (VNT) in patients with compensated chronic liver disease. We aimed to improve these tests by including data on the ratio of platelets to liver stiffness.Methods: In a retrospective analysis of data from 10 study populations, collected from 2004 through 2018, we randomly assigned data from 2368 patients with chronic liver disease of different etiologies to a derivation population (n = 1579; 15.1% with VNT, 50.2% with viral hepatitis, 28.9% with nonalcoholic fatty liver disease, 20.8% with alcohol-associated liver disease, with model for end-stage liver disease scores of 9.5 ± 3.0, and 93.0% with liver stiffness measurements ≥10 kPa) or a validation population (n = 789). Test results were compared with results from a sequential algorithm (VariScreen). VariScreen incorporated data on platelets or liver stiffness measurements and then the ratio of platelets to liver stiffness measurement, adjusted for etiology, patient sex, and international normalized ratio.Results: In the derivation population, endoscopies were spared for 23.9% of patients using the B6C (VNT missed in 2.9%), 24.3% of patients using the ANTICIPATE score (VNT missed in 4.6%), 34.5% of patients using VariScreen (VNT missed in 2.9%), and 41.9% of patients using the EB6C (VNT missed in 10.9%). Differences in spared endoscopy rates were significant (P ≤ .001), except for B6C vs ANTICIPATE and in missed VNT only for EB6C vs the others (P ≤ .009). VariScreen was the only safe test regardless of sex or etiology (missed VNT ≤5%). Moreover, VariScreen secured screening without missed VNT in patients with model for end-stage liver disease scores higher than 10. This overall strategy performed better than a selective strategy restricted to patients with compensated liver disease. Test performance and safety did not differ significantly among populations.Conclusions: In a retrospective study of data from 2368 patients with chronic liver disease, we found that the B6C are safe whereas the EB6C are unsafe, based on missed VNT. The VariScreen algorithm performed well in patients with chronic liver disease of any etiology or severity. It is the only test that safely rules out VNT and can be used in clinical practice.
Published: 2021

11. Personalized surveillance for hepatocellular carcinoma in cirrhosis – using machine learning adapted to HCV status

Author: Jean-Marie Péron, Dominique Larrey, Albert Tran, Marc Bourlière, Paul Calès, Thong Dao, Eric Nguyen-Khac, Olivier Chazouillères, Brigitte Bernard-Chabert, Pierre Attali, Ghassan Riachi, Jean-Didier Grangé, Dominique Guyader, Pierre Nahon, Victor de Ledinghen, Claire Wartelle, Ariane Mallat, Christos Christidis, Christophe Pilette, Vincent Di Martino, Jean-Pierre Bronowicki, Stanislas Pol, Philippe Mathurin, Dominique Roulot, Denis Ouzan, Jean-Frédéric Blanc, Louis d’Alteroche, David Zucman, Jean-Pierre Zarski, Tarik Asselah, Etienne Audureau, Dominique Thabut, Angela Sutton, Fabien Zoulim, Laurent Alric, Carole Cagnot, Christine Silvain, Armand Abergel, Richard Layese, Fabrice Carrat, Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ANRS France Recherche Nord & sud Sida-hiv hépatites, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Institut Arnault Tzanck, Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Hôpital Michallon, Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Agence Nationale de Recherches sur le Sida et les Hépatites Virales, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées
Subjects: 0301 basic medicine, Cirrhosis, [SDV]Life Sciences [q-bio], Machine learning, computer.software_genre, HCV clearance, 03 medical and health sciences, 0302 clinical medicine, medicine, ComputingMilieux_MISCELLANEOUS, Prothrombin time, Hepatology, medicine.diagnostic_test, business.industry, Incidence (epidemiology), Cancer, medicine.disease, digestive system diseases, 3. Good health, 030104 developmental biology, Hepatocellular carcinoma, Cohort, Screening, 030211 gastroenterology & hepatology, Artificial intelligence, Liver cancer, business, Risk assessment, computer
Abstract: Background & Aims Refining hepatocellular carcinoma (HCC) surveillance programs requires improved individual risk prediction. Thus, we aimed to develop algorithms based on machine learning approaches to predict the risk of HCC more accurately in patients with HCV-related cirrhosis, according to their virological status. Methods Patients with compensated biopsy-proven HCV-related cirrhosis from the French ANRS CO12 CirVir cohort were included in a semi-annual HCC surveillance program. Three prognostic models for HCC occurrence were built, using (i) Fine-Gray regression as a benchmark, (ii) single decision tree (DT), and (iii) random survival forest for competing risks survival (RSF). Model performance was evaluated from C-indexes validated externally in the ANRS CO22 Hepather cohort (n = 668 enrolled between 08/2012–01/2014). Results Out of 836 patients analyzed, 156 (19%) developed HCC and 434 (52%) achieved sustained virological response (SVR) (median follow-up 63 months). Fine-Gray regression models identified 6 independent predictors of HCC occurrence in patients before SVR (past excessive alcohol intake, genotype 1, elevated AFP and GGT, low platelet count and albuminemia) and 3 in patients after SVR (elevated AST, low platelet count and shorter prothrombin time). DT analysis confirmed these associations but revealed more complex interactions, yielding 8 patient groups with varying cancer risks and predictors depending on SVR achievement. On RSF analysis, the most important predictors of HCC varied by SVR status (non-SVR: platelet count, GGT, AFP and albuminemia; SVR: prothrombin time, ALT, age and platelet count). Externally validated C-indexes before/after SVR were 0.64/0.64 [Fine-Gray], 0.60/62 [DT] and 0.71/0.70 [RSF]. Conclusions Risk factors for hepatocarcinogenesis differ according to SVR status. Machine learning algorithms can refine HCC risk assessment by revealing complex interactions between cancer predictors. Such approaches could be used to develop more cost-effective tailored surveillance programs. Lay summary Patients with HCV-related cirrhosis must be included in liver cancer surveillance programs, which rely on ultrasound examination every 6 months. Hepatocellular carcinoma (HCC) screening is hampered by sensitivity issues, leading to late cancer diagnoses in a substantial number of patients. Refining surveillance periodicity and modality using more sophisticated imaging techniques such as MRI may only be cost-effective in patients with the highest HCC incidence. Herein, we demonstrate how machine learning algorithms (i.e. data-driven mathematical models to make predictions or decisions), can refine individualized risk prediction.
Published: 2020

12. 21 Co-infection par le virus de l’hépatite B et le virus de l’hépatite C

Author: Jean-Pierre Zarski and Vincent Leroy
Published: 2020

13. Contribution of the ELFG test in algorithms of non-invasive markers towards the diagnosis of significant fibrosis in chronic hepatitis C.

Author: Jean-Pierre Zarski, Nathalie Sturm, Jérôme Guechot, Elie-Serge Zafrani, Michel Vaubourdolle, Sophie Thoret, Jennifer Margier, Sandra David-Tchouda, and Jean-Luc Bosson
Subjects: Medicine, Science
Abstract: BACKGROUND AND AIMS: We aimed to determine the best algorithms for the diagnosis of significant fibrosis in chronic hepatitis C (CHC) patients using all available parameters and tests. PATIENTS AND METHODS: We used the database from our study of 507 patients with histologically proven CHC in which fibrosis was evaluated by liver biopsy (Metavir) and tests: Fibrometer®, Fibrotest®, Hepascore®, Apri, ELFG, MP3, Forn's, hyaluronic acid, tissue inhibitor of metalloproteinase-1 (TIMP1), MMP1, collagen IV and when possible Fibroscan™. For the first test we used 90% negative predictive value to exclude patients with F≤1, next an induction algorithm was applied giving the best tests with at least 80% positive predictive value for the diagnosis of F≥2. The algorithms were computed using the R Software C4.5 program to select the best tests and cut-offs. The algorithm was automatically induced without premises on the part of the investigators. We also examined the inter-observer variations after independent review of liver biopsies by two pathologists. A medico-economic analysis compared the screening strategies with liver biopsy. RESULTS: In "intention to diagnose" the best algorithms for F≥2 were Fibrometer ®, Fibrotest®, or Hepascore® in first intention with the ELFG score in second intention for indeterminate cases. The percentage of avoided biopsies varied between 50% (Fibrotest® or Fibrometer®+ELFG) and 51% (Hepascore®+ELFG). In "per-analysis" Fibroscan™+ELFG avoided liver biopsy in 55% of cases. The diagnostic performance of these screening strategies was statistically superior to the usual combinations (Fibrometer® or Fibrotest®+Fibroscan™) and was cost effective. We note that the consensual review of liver biopsies between the two pathologists was mainly in favor of F1 (64-69%). CONCLUSION: The ELFG test could replace Fibroscan in most currently used algorithms for the diagnosis of significant fibrosis including for those patients for whom Fibroscan™ is unusable.
Published: 2013
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14. Non-invasive fibrosis tests to predict complications in compensated post-hepatitis C cirrhosis

Author: Carole Cagnot, Etienne Audureau, Marianne Ziol, Candice Trocmé, Françoise Roudot-Thoraval, Angela Sutton, Antoine Vilotitch, Marie-Noëlle Hilleret, Jennifer Margier, Jean-Pierre Zarski, Richard Layese, Pierre Nahon, Valerie Boursier, Sandra David-Tchouda, and CHU Grenoble
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, [SDV]Life Sciences [q-bio], Population, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Fibrosis, Internal medicine, medicine, Humans, education, Aged, education.field_of_study, Hepatology, business.industry, Liver Diseases, Hepatitis C, Middle Aged, medicine.disease, 3. Good health, Case-Control Studies, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Propensity score matching, Female, 030211 gastroenterology & hepatology, Complication, business, Hepatic decompensation
Abstract: Markers predicting complications of post-hepatitis C cirrhosis are needed. We asked whether changes in noninvasive markers of fibrosis can predict liver-related complications.This was a case-controlled study using a prospective national cohort (ANRS-CO12-CIRVIR) of 1323 HCV-infected patients with compensated cirrhosis: 97 patients who developed liver-related complications such as hepatocellular carcinoma or hepatic decompensation (cases) matched in age, sex and follow-up duration were compared with 257 patients without complications (controls). Actitest/Fibrotest™, Inflameter/Fibrometer™, ELF™ and Fibroscan™ were performed at baseline and yearly. Samples based on Propensity score matching were built and mixed linear models performed. Outcomes in a sustained virological response (SVR) negative population and a SVR-positive population were also described.At baseline, all characteristics of patients were similar between the groups. All fibrosis tests were statistically higher for cases compared to controls, Fibroscan™ excepted: Fibrotest™: 0.83±0.13 vs. 0.77±0.16; Fibrometer™: 0.93±0.07 vs. 0.90±0.11; ELF™: 11.4±1.0 vs. 11.0±1.2 (P0.02). The mean follow-up was 5.7±1.9 years. Over a 3-year period, the significant difference in fibrosis marker values between cases and controls remained constant; with a trend toward a decrease in inflammation markers in controls, independent of SVR status.Baseline noninvasive serum fibrosis and inflammation markers were significantly higher in patients developing a complication than in controls. During the follow-up only inflammatory markers decreased in controls, but not in cases, and thus could potentially be used to predict the occurrence of complications in cirrhotic patients.
Published: 2020

15. Early hepatocellular carcinoma detection using magnetic resonance imaging is cost-effective in high-risk patients with cirrhosis

Author: Pierre Nahon, Marie Najean, Richard Layese, Kevin Zarca, Laeticia Blampain Segar, Carole Cagnot, Nathalie Ganne-Carrié, Gisèle N’Kontchou, Stanislas Pol, Cendrine Chaffaut, Fabrice Carrat, Maxime Ronot, Etienne Audureau, Isabelle Durand-Zaleski, Tarik Asselah, Dominique Guyader, Hélène Fontaine, Georges-Philippe Pageaux, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Thomas Decaensi, Ghassan Riachi, Paul Calès, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, Sebastien Dharancy, Jean-Frédéric Blanc, Armand Abergel, Olivier Chazouillères, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Louis d’Alteroche, Claire Wartelle, Thông Dao, Dominique Thabut, Christophe Pilette, Christine Silvain, Christos Christidis, Eric Nguyen-Khac, Brigitte Bernard-Chabert, Sophie Hillaire, Vincent Di Martino, Delphine Bonnet, Virginie Payssan-Sicart, Chloe Pomes, François Bailly, Marjolaine Beaudoin, Dominique Giboz, Kerstin Hartig-Lavie, Marianne Maynard, Eric Billaud, David Boutoille, Morane Cavellec, Marjorie Cheraud-Carpentier, Isabelle Hubert, Jaouad Benhida, Adrien Lannes, Françoise Lunel, Frédéric Oberti, Nathalie Boyer, Nathalie Giuily, Corinne Castelnau, Giovanna Scoazec, Aziza Chibah, Sylvie Keser, Karim Bonardi, Anaïs Vallet-Pichard, Philippe Sogni, Juliette Foucher, Jean-Baptiste Hiriart, Amy Wilson, Sarah Shili, Faiza Chermak, Christelle Ansaldi, Nisserine Ben Amara, Laëtitia Chouquet, Emilie De Luca, Valérie Oules, Rodolphe Anty, Eve Gelsi, Régine Truchi, Elena Luckina, Nadia Messaoudi, Joseph Moussali, Barbara De Dieuleveult, Damien Labarriere, Pascal Poter, Si Nafa Si Ahmed, Véronique Grando-Lemaire, Valérie Bourcier, Séverine Brulé, Thomas Stalhberger, Caroline Jezequel, Audrey Brener, Anne Laligant, Aline Rabot, Isabelle Renard, Thomas F. Baumert, Michel Dofföel, Catherine Mutter, Pauline Simo-Noumbissie, Esma Razi, Hélène Barraud, Mouni Bensenane, Abdelbasset Nani, Sarah Hassani-Nani, Marie-Albertine Bernard, Michael Bismuth, Ludovic Caillo, Stéphanie Faure, Marie Pierre Ripault, Christophe Bureau, Jean Marie Peron, Marie Angèle Robic, Léa Tarallo, Marine Faure, Bruno Froissart, Marie-Noelle Hilleret, Jean-Pierre Zarski, Odile Goria, Victorien Grard, Hélène Montialoux, Muriel François, Christian Ouedraogo, Christelle Pauleau, Anne Varault, Tony Andreani, Bénédicte Angoulevant, Azeline Chevance, Lawrence Serfaty, Teresa Antonini, Audrey Coilly, Jean-Charles Duclos Vallée, Mariagrazia Tateo, Corinne Bonny, Chanteranne Brigitte, Géraldine Lamblin, Léon Muti, Abdenour Babouri, Virginie Filipe, Camille Barrault, Laurent Costes, Hervé Hagège, Soraya Merbah, Paul Carrier, Maryline Debette-Gratien, Jérémie Jacques, Guillaume Lassailly, Florent Artu, Valérie Canva, Sébastien Dharancy, Alexandre Louvet, Marianne Latournerie, Marc Bardou, Thomas Mouillot, Yannick Bacq, Didier Barbereau, Charlotte Nicolas, Caroline Chevalier, Isabelle Archambeaud, Sarah Habes, Danièle Botta-Fridlund, Eric Saillard, Marie-Josée Lafrance, Patrice Cacoub, Patrizia Carrieri, Elisabeth Delarocque-Astagneau, Victor De Ledinghen, Céline Dorival, Jean Dubuisson, Chantal Housset, Dominique Larrey, Patrick Marcellin, Jean-Michel Pawlotsky, Ventzislava Petrov-Sanchez, Sophie Vaux, Linda Wittkop, Yazdan Yazdanpanah, Jessica Zucman-Rossi, Christophe Moreno, Romain Moirand, Nicolas Carbonell, Jean-Charles Duclos-Vallée, Victor de Ledinghen, Violaine Ozenne, Jean Henrion, Gabriel Perlemuter, Xavier Amiot, Sylvie Chevret, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Henri Mondor, Unité de recherche clinique en économie de la santé [Paris] (URC Eco), Délégation de la Recherche Clinique et de l’Innovation [Paris] (DRCI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ANRS|Maladies infectieuses émergentes (ANRS|MIE), Université Sorbonne Paris Nord, Hôpital Cochin [AP-HP], Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de santé publique [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Hôpital Beaujon [AP-HP]
Subjects: AMRI, abbreviated magnetic resonance imaging, NAFLD, non-alcoholic fatty liver disease, medicine.medical_specialty, Cirrhosis, Cost effectiveness, [SDV]Life Sciences [q-bio], Population, TACE, transarterial chemoembolization, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Gastroenterology, QALY, quality-adjusted life year, Internal medicine, Internal Medicine, LY, life years, Immunology and Allergy, Medicine, Early Hepatocellular Carcinoma, liver cancer risk, education, cost-effectiveness, RFA, radiofrequency ablation, education.field_of_study, AFP, alpha-fetoprotein, US, ultrasound, Hepatology, medicine.diagnostic_test, business.industry, cirrhosis, LYG, life years gained, Incidence (epidemiology), BCLC, Barcelona Clinic Liver Cancer, ICER, incremental cost-effectiveness ratio, Magnetic resonance imaging, medicine.disease, HR, hazard ratio, digestive system diseases, Hepatocellular carcinoma, SHR, subdistribution hazard ratio, surveillance, HCC, hepatocellular carcinoma, business, MRI, magnetic resonance imaging, Incremental cost-effectiveness ratio, Research Article, MRI
Abstract: Background & Aims Reinforced hepatocellular carcinoma (HCC) surveillance using magnetic resonance imaging (MRI) could increase early tumour detection but faces cost-effectiveness issues. In this study, we aimed to evaluate the cost-effectiveness of MRI for the detection of very early HCC (Barcelona Clinic Liver Cancer [BCLC] 0) in patients with an annual HCC risk >3%. Methods French patients with compensated cirrhosis included in 4 multicentre prospective cohorts were considered. A scoring system was constructed to identify patients with an annual risk >3%. Using a Markov model, the economic evaluation estimated the costs and life years (LYs) gained with MRI vs. ultrasound (US) monitoring over a 20-year period. The incremental cost-effectiveness ratio (ICER) was calculated by dividing the incremental costs by the incremental LYs. Results Among 2,513 patients with non-viral causes of cirrhosis (n = 840) and/or cured HCV (n = 1,489)/controlled HBV infection (n = 184), 206 cases of HCC were detected after a 37-month follow-up. When applied to training (n = 1,658) and validation (n = 855) sets, the construction of a scoring system identified 33.4% and 37.5% of patients with an annual HCC risk >3% (3-year C-Indexes 75 and 76, respectively). In patients with a 3% annual risk, the incremental LY gained with MRI was 0.4 for an additional cost of €6,134, resulting in an ICER of €15,447 per LY. Compared to US monitoring, MRI detected 5x more BCLC 0 HCC. The deterministic sensitivity analysis confirmed the impact of HCC incidence. At a willingness to pay of €50,000/LY, MRI screening had a 100% probability of being cost-effective. Conclusions In the era of HCV eradication/HBV control, patients with annual HCC risk >3% represent one-third of French patients with cirrhosis. MRI is cost-effective in this population and could favour early HCC detection. Lay summary The early identification of hepatocellular carcinoma in patients with cirrhosis is important to improve patient outcomes. Magnetic resonance imaging could increase early tumour detection but is more expensive and less accessible than ultrasound (the standard modality for surveillance). Herein, using a simple score, we identified a subgroup of patients with cirrhosis (accounting for >one-third), who were at increased risk of hepatocellular carcinoma and for whom the increased expense of magnetic resonance imaging would be justified by the potential improvement in outcomes., Graphical abstract, Highlights • HCC risk stratification in patients with cirrhosis aims at improving performance of cancer surveillance. • Using a simple scoring system, one-third of patients with cirrhosis with an annual HCC risk >3% can be easily identified. • Semi-annual surveillance using MRI in this population could enable the cost-effective detection of 5x more BCLC 0 HCCs.
Published: 2022

16. Extrahepatic cancers are the leading cause of death in patients achieving hepatitis B virus control or hepatitis C virus eradication

Author: Thong Dao, Pierre Nahon, Christos Christidis, Jean-Pierre Zarski, Pierre Attali, Valérie Bourcier, Ghassan Riachi, Victor de Ledinghen, Laurent Alric, Dominique Thabut, Claire Wartelle, Eric Nguyen-Khac, Patrick Marcellin, Carole Cagnot, Dominique Roulot, Christophe Pilette, Armand Abergel, Fabien Zoulim, Vincent Di Martino, Eric Letouzé, Richard Layese, Jean-Pierre Bronowicki, Jean-Frédéric Blanc, Christine Silvain, Ariane Mallat, Stanislas Pol, Denis Ouzan, Jean-Didier Grangé, Angela Sutton, Jean-Marie Péron, Brigitte Bernard-Chabert, Dominique Larrey, Albert Tran, David Zucman, Marc Bourlière, Etienne Audureau, Lawrence Serfaty, Manon Allaire, Paul Calès, Yannick Bacq, Dominique Guyader, Philippe Mathurin, Françoise Roudot-Thoraval, Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), ANRS France Recherche Nord & sud Sida-hiv hépatites, Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'hépatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut Arnault Tzanck, Hospices Civils de Lyon (HCL), Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département d'hépato-gastroentérologie, CHU Grenoble-Université Grenoble Alpes (UGA), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Hôpital Claude Huriez [Lille], CHU Lille, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Tenon [AP-HP], Onxeo S.A., Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier d'Aix en Provence [Aix-en-Provence] (CHIAP ), CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Le Mans (CH Le Mans), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hellenic Open University [Patras], Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 (GRAP), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Foch [Suresnes], Service d'Hépatologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ANRS (France Recherche Nord & sud Sida‐HIV Hépatites‐FRENCH)HECAM (Hepatocellular Carcinoma Multi‐Technological) Consortium, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], CHU Saint-Eloi, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre d'investigation de la fibrose hépatique [CHU de Bordeaux] (Hôpital Haut-Lévêque ), Hôpital Haut-Lévêque [CHU de Bordeaux], Université Nice Sophia Antipolis (... - 2019) (UNS), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), SIGMA Clermont, Hépatologie Gastro-Entérologie, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service d'hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UMR INSERM U955, École nationale vétérinaire d'Alfort (ENVA), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépato-gastroentérologie [CHU Amiens-Picardie], Service de Médecine Interne [Hôpital Foch, Suresnes] (SMI), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Grenoble Alpes (UGA)-CHU Grenoble, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], CHU Trousseau [APHP], and Univ Angers, Okina
Subjects: Liver Cirrhosis, Male, Cirrhosis, Databases, Factual, [SDV]Life Sciences [q-bio], medicine.disease_cause, Gastroenterology, Cohort Studies, 0302 clinical medicine, Neoplasms, Prospective Studies, education.field_of_study, Hepatocellular / virology, Liver Neoplasms, Liver Neoplasms / epidemiology, Hepatitis C, Middle Aged, Hepatitis B, Prognosis, 3. Good health, 030220 oncology & carcinogenesis, Disease Progression, Female, Liver Cirrhosis / epidemiology, 030211 gastroenterology & hepatology, France, Databases Factual, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Hepatitis C virus, Antiviral Agents / therapeutic use, Population, Liver Neoplasms / pathology, Chronic / complications, Antiviral Agents, Risk Assessment, Article, Liver Cirrhosis / virology, 03 medical and health sciences, Hepatitis B, Chronic, Liver Cirrhosis / physiopathology, Internal medicine, medicine, Humans, education, Aged, Hepatitis B virus, Chronic / drug therapy, Neoplasms / pathology, Hepatology, business.industry, Carcinoma, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Chronic, medicine.disease, Chronic / pathology, Survival Analysis, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatocellular / epidemiology, Liver Neoplasms / virology, Neoplasms / virology Prognosis, Carcinom, Standardized mortality ratio, Hepatocellular / pathology, Male Middle Aged Neoplasms / mortality, business
Abstract: Comment in Does cirrhosis associated with well controlled viral hepatitis confer a risk for extrahepatic cancer? Yang JD, Gores GJ. Hepatology. 2018 Oct;68(4):1217-1219. doi: 10.1002/hep.30063. Epub 2018 Jul 10.; International audience; Data on extrahepatic cancers (EHCs) in compensated viral cirrhosis are limited. The objective of the prospective multicenter Agence Nationale de Recherche sur le SIDA et les Hépatites virales CO12 CirVir cohort was to assess the occurrence of all clinical events in patients with compensated viral cirrhosis, including all types of cancer. Patients with the following inclusion criteria were enrolled in 35 French centers: (1) biopsy-proven hepatitis B virus (HBV) or hepatitis C virus (HCV) cirrhosis, (2) Child-Pugh A, or (3) absence of previous liver complications including primary liver cancer (PLC). Patients were followed up prospectively every 6 months. The standardized mortality ratio (SMR) was calculated according to age and gender using 5-year periods. The impact of sustained viral response (SVR) in HCV patients and maintained viral suppression in HBV patients were assessed using time-dependent analysis. A total of 1,671 patients were enrolled between 2006 and 2012 (median age, 54.9 years; men, 67.3%; HCV, 1,323; HBV, 317; HCV-HBV, 31). Metabolic features and excessive alcohol and tobacco consumption were recorded in 15.2%, 36.4%, and 56.4% of cases, respectively. After a median follow-up of 59.7 months, 227 PLCs were diagnosed (5-year cumulative incidence [CumI] 13.4%) and 93 patients developed EHC (14 patients with lymphoid or related tissue cancer and 79 with solid tissue cancer; 5-year EHC CumI, 5.9%). Compared to the general French population, patients were younger at cancer diagnosis, with significantly higher risk of EHC in HCV patients (SMR, 1.31; 95 confidence interval [CI], 1.04-1.64; P = 0.017) and after SVR (SMR = 1.57; 95% CI, 1.08-2.22; P = 0.013). EHC was the fourth leading cause of death in the whole cohort and the first in patients with viral control/eradication.CONCLUSION: Compared to the general French population, HCV cirrhosis is associated with a higher risk of EHC and the first cause of death in patients with viral cirrhosis who achieve virological control/eradication. (Hepatology 2018).
Published: 2018

17. Lack of evidence of sustained hematopoietic reconstitution after transplantation of unmanipulated adult liver stem cells in monkeys

Author: Michel Drouet, Jean-François Mayol, Françoise Norol, André Peinnequin, Jean-Pierre Zarski, Christian Létoublon, and Francis Hérodin
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: The aim of this study was to search for hematopoietic potential in the liver of non-human primates. Lethally irradiated (2×5 Gy γ) Cynomolgus macaques were given autologous hepatic mononuclear cells (HMNC) isolated from a liver lobe by perfusion and digestion with 0.1% collagenase. Two monkeys were given intramedullary injections of HMNC (18.6×106/kg, 20.4×106/kg) and two others were co-transplanted with HMNC (14.35×106/kg, 96.5×106/kg) and bone marrow mesenchymal stem cells (0.42×106/kg, 1.16×106/kg). All monkeys exhibited a transient neutrophil recovery from day 22 for 10 days, but failed to produce platelets and remained transfusion-dependent. In conclusion, adult liver stem cells from a monkey model show a low level of in vivo hematopoietic potential, suggesting ex vivo manipulation will be required before clinical use of such cells.
Published: 2007
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18. Prognostic value of viral eradication for major adverse cardiovascular events in hepatitis C cirrhotic patients

Author: Patrice Cacoub, Pierre Nahon, Richard Layese, Lorraine Blaise, Anne Claire Desbois, Valérie Bourcier, Carole Cagnot, Patrick Marcellin, Dominique Guyader, Stanislas Pol, Dominique Larrey, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Jean-Pierre Zarski, Ghassan Riachi, Paul Calès, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, Jean-Frédéric Blanc, Armand Abergel, Lawrence Serfaty, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Yannick Bacq, Claire Wartelle, Thông Dao, Dominique Thabut, Christophe Pilette, Christine Silvain, Christos Christidis, Dominique Capron, Gérard Thiefin, David Zucman, Vincent Di Martino, Corinne Isnard Bagnis, Marianne Ziol, Angela Sutton, Eric Letouze, Françoise Roudot-Thoraval, Etienne Audureau, Hélène Fontaine, Vincent Leroy, Sebastien Dharancy, Yves Benhamou, Sophie Hillaire, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunologie - Immunopathologie - Immunothérapie (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Pôle Recherche Clinique-Santé Publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Université Sorbonne Paris Nord - UFR des Sciences de la communication (USPN UP13 UFR SC), Université Sorbonne Paris Nord, Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Département d'hépatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut Arnault Tzanck, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Avicenne [AP-HP], Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Département d'hépato-gastroentérologie, CHU Grenoble-Université Grenoble Alpes (UGA), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Hôpital Claude Huriez [Lille], CHU Lille, Hôpital Saint-André, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, CHU Saint-Antoine [AP-HP], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Tenon [AP-HP], Hôpital Paul Brousse, Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier d'Aix en Provence [Aix-en-Provence] (CHIAP ), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Le Mans (CH Le Mans), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Mutualiste de Montsouris (IMM), Institut mutualiste Monsouris (IMM), Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Foch [Suresnes], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), ANRS CO12 CirVir group : Pierre Nahon, Patrick Marcellin, Dominique Guyader, Stanislas Pol, Hélène Fontaine, Dominique Larrey, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Jean-Pierre Zarski, Vincent Leroy, Ghassan Riachi, Paul Calès, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, Sebastien Dharancy, Jean-Frédéric Blanc, Armand Abergel, Lawrence Serfaty, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Yannick Bacq, Claire Wartelle, Thông Dao, Yves Benhamou, Christophe Pilette, Christine Silvain, Christos Christidis, Dominique Capron, Gérard Thiefin, Sophie Hillaire, Vincent Di Martino, Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Service de Gastro-entérologie - Hépatologie [Purpan], CHU Toulouse [Toulouse], Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], CHU Trousseau [APHP], Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Service de Néphrologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Universités, Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], ANRS France Recherche Nord & sud Sida-hiv hépatites, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie du système immunitaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Cochin [AP-HP], CHU Saint-Eloi, Centre d'investigation de la fibrose hépatique [CHU de Bordeaux] (Hôpital Haut-Lévêque ), Hôpital Haut-Lévêque [CHU de Bordeaux], Service de Gastro-entérologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Hôpital Purpan [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 6602, Institut Pascal, Université Clermont Auvergne (UCA), Centre National de la Recherche Scientifique (CNRS), SIGMA Clermont, Hépatologie Gastro-Entérologie, Centre Hospitalier Universitaire Estaing, Institut Pascal - Clermont Auvergne (IP), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Service d'hépatologie [Saint-Antoine], Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), UMR INSERM U955, École nationale vétérinaire d'Alfort (ENVA), CHU Tenon [APHP], Onxeo S.A., CHU Trousseau [APHP]-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Hellenic Open University [Patras], Service d'Hépatogastroentérologie, CHU Amiens-Picardie, Service de Médecine Interne [Hôpital Foch, Suresnes] (SMI), Service d'Hépatologie, Hôpital Jean Minjoz, Centre Hospitalier Universitaire de Besançon, Université de Franche Comté, Hôpital Jean Minjoz, Service d'Explorations Fonctionnelles Neurologie [CHU Pitié-Salpêtrière], Université Sorbonne Paris Cité (USPC), Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13), Equipe labellisée Ligue Contre le Cancer [Saint-Denis], Université Paris 13 (UP13)-PRES Sorbonne Paris Cité, Service d'hépatologie [CHU Pontchaillou], Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de pathologie [Hôpital Haut Lévêque], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Service d'Hépatologie [Hôtel-Dieu], Hôpital Hôtel-Dieu [Paris], Service d'Hépatologie [Avicenne], Service d'Hépatologie [Nancy], Département d'hépatologie (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD), Service d'hépatologie [CHU Saint-Antoine], Service d'Hépatologie, Hôpital Henri Mondor, AP-HP, Créteil, France., Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Service de néphrologie [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupe Hospitalier Universitaire Paris Seine-Saint-Denis (GHUPSSD), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Sigma CLERMONT (Sigma CLERMONT)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Grenoble Alpes (UGA)-CHU Grenoble, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP]
Subjects: Male, Liver Cirrhosis, Survival rate, Cirrhosis, Biopsy, [SDV]Life Sciences [q-bio], Kaplan-Meier Estimate, Gastroenterology, Severity of Illness Index, Cohort Studies, 0302 clinical medicine, Liver Function Tests, Prevalence, Needle, 030212 general & internal medicine, Myocardial infarction, Chronic, medicine.diagnostic_test, Biopsy, Needle, Hepatitis C, Middle Aged, Prognosis, Immunohistochemistry, 3. Good health, Cardiovascular Diseases, Predictive value of tests, 030211 gastroenterology & hepatology, Female, France, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Antiviral Agents, Risk Assessment, 03 medical and health sciences, Age Distribution, Predictive Value of Tests, Internal medicine, medicine, Humans, cardiovascular diseases, Sex Distribution, Aged, Proportional Hazards Models, Retrospective Studies, business.industry, Hepatitis C, Chronic, medicine.disease, Heart failure, business, Liver function tests, Mace
Abstract: International audience; BACKGROUND: The objective was to examine the role of a sustained virological response (SVR) on major adverse cardiovascular events (MACEs) in patients with compensated hepatitis C virus (HCV) cirrhosis.METHODS: Patients with the following criteria were enrolled in 35 French centers: (1) biopsy-proven HCV cirrhosis; (2) Child-Pugh A; (3) positive viremia; and (4) no prior liver complication, and then prospectively followed. All patients received HCV treatment after inclusion. MACEs included stroke, myocardial infarction, ischemic heart disease, heart failure, peripheral arterial disease, cardiac arrest, and cardiovascular death. SVR, defined as negative viremia 12 weeks posttreatment, was considered as a time-dependent covariate, and its effect on MACE occurrence was assessed. The median follow up was 57.5 months, ending in December 2015.RESULTS: Sixty-two of 878 (7.1%) patients presented a total of 79 MACEs. The main predictive baseline factors of MACEs were Asian ethnic origin, history of MACEs, arterial hypertension, diabetes mellitus, current smoking, low serum albumin level, high total bilirubin level, and low platelet count. In multivariate analysis, SVR was associated with a decreased risk of MACEs (hazard ratio=0.35, 95% CI 0.09-0.97, P=.044), whereas Asian ethnic origin, arterial hypertension, smoking, and low serum albumin level remained predictive of MACE occurrence. The 5-year survival rate was 60.1% versus 87.5% in patients who did versus those who did not present a MACE (PCONCLUSIONS: In patients with compensated HCV-related cirrhosis, Asian ethnic origin, arterial hypertension, smoking, and low serum albumin are independent predictive factors of cardiovascular events, whereas an SVR is associated with a decreased rate of cardiovascular events.
Published: 2018

19. Prognosis of alcoholic or viral B/C cirrhosis according to ABO blood group: results of abocirralvir, from CIRRAL and ANRS CO12 CirVir cohorts

Author: Isabelle Ollivier-Hourmand, Pierre Nahon, Cendrine Chaffaut, Thong Dao, Nga Nguyen, Marcellin Patrick, Dominique Roulot, Victor de Lédinghen, Stanislas Pol, Dominique Guyader, Isabelle Mabile-Archambeaud, Fabien Zoulim, Frédéric Oberti, Albert Tran, Jean-Pierre Bronowicki, Louis Dalteroche, Denis Ouzan, Jean Marie Peron, Jean-Pierre Zarski, Marc Bourliere, Dominique Larrey, Alexandre Louvet, Paul Cales, Armand Abergel, Philippe Mathurin, Ariane Mallat, Jean-Frédéric Blanc, Eric Nguyen Khac, Ghassan Riachi, Laurent Alric, Lawrence Serfaty, Tereza Antonini, Christophe Moreno, Pierre Attali, Dominique Thabut, Christophe Pilette, Jean Didier Grange, Christine Silvain, Nicolas Carbonell, Brigitte Bernard Chabert, Odile Goria, Claire Wartelle-Bladou, Romain Moirand, Christos Christidis, Gabriel Perlemuter, Violaine Ozenne, Jean Henrion, Sophie Hillaire, Vincent Di Martino, Xavier Amiot, Angela Sutton, Nathalie Barget, Yohann Repesse, Sylvie Chevret, and Nathalie Ganne-Carrié
Subjects: Hepatology
Published: 2020

20. Doxorubicin-loaded nanoparticles for patients with advanced hepatocellular carcinoma after sorafenib treatment failure (RELIVE): a phase 3 randomised controlled trial

Author: Inmaculada Ales, Hakan Harputluoglu, Marc Peeters, Jean-Marc Phelip, G. Pelletier, Zsuzsanna Kahan, Alice Gangloff, Fadi Farhat, Imam Waked, Luc Lasser, René Gerolami, Giovanni Luca, Thomas Berg, Julie Le Boulicaut, Jean-Pierre Zarski, Ivan Borbath, Wolfgang Sieghart, Ozlem Ata, Howard Ozer, Julie Vincent, Thierry Fontanges, Bartomeu Massuti, Christos Galanopoulos, Mohammed El Kassas, Audrey Molé, Imam Wakid, Philippe Merle, Nasr El Lahlouby, Andreas Maieron, Marilyne Debette-Gratien, Antonio Cubillo, György Bodoky, Sylvain Manfredi, Faiza Khemissa-Akouz, Jawad Makarem, Jean-Frédéric Blanc, Ahmet Coker, Carmen Guillén, Massimo Colombo, Michael Schultheiß, Joerg Trojan, Yann Touchefeu, Isabelle Ollivier-Hourmand, François Habersetzer, Vlad Ratziu, Amr Abdel, Amr S Saad, Miguel Marín, Magdolna Dank, Mohamed Bouattour, Hélène Regnault, Jean-Didier Grangé, Pierluigi Toniutto, Hanaa Kohail, Sameh Shamaa, Carine Richou, Erdem Goker, Eric Nguyen-Khac, Oscar Alabiso, G.-P. Pageaux, Andrea Casadei-Gardini, Moses Raj, Alexander Zipprich, Henning Wege, Ilkay Tugba, Aurore Baron, Victor Navarro, Domenico Amoroso, Issam Chehade, Nashat Gabrail, Pierre Attali, Barbara Dauvois, Stefano Tamberi, Driffa Moussata, Angela Buonadonna, Emiliano Tamburini, Muhammet Ali, Armand Abergel, Albert Tran, Suayib Yalcin, Ursula Ehmer, Hermini Manzano, Jean Delwaide, Andrés Muñoz, Carlos López, Jean-Pierre Bronowicki, Zsolt Horváth, Alper Sevinc, Gloria Sánchez, Ralph Hauke, Gabriele Luppi, Bérangère Vasseur, Nelson S. Yee, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance Publique-Hôpitaux de Marseille (AP-HM), Hôpital Charles Nicolle [Rouen]-CHU Rouen, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (SLuc) Service de gastro-entérologie, Merle, P., Blanc, J. -F., Phelip, J. -M., Pelletier, G., Bronowicki, J. -P., Touchefeu, Y., Pageaux, G., Gerolami, R., Habersetzer, F., Nguyen-Khac, E., Casadei-Gardini, A., Borbath, I., Tran, A., Wege, H., Saad, A. S., Colombo, M., Abergel, A., Richou, C., Waked, I., Yee, N. S., Mole, A., Attali, P., Le Boulicaut, J., Vasseur, B., Moussata, D., Grange, J. -D., Ratziu, V., Khemissa-Akouz, F., Regnault, H., Dauvois, B., Zarski, J. -P., Ollivier-Hourmand, I., Manfredi, S., Debette-Gratien, M., Gangloff, A., Fontanges, T., Baron, A., Bouattour, M., Vincent, J., Sieghart, W., Maieron, A., Peeters, M., Delwaide, J., Lasser, L., Berg, T., Schultheiss, M., Zipprich, A., Trojan, J., Ehmer, U., Luppi, G., Luca, G., Tamberi, S., Amoroso, D., Alabiso, O., Buonadonna, A., Toniutto, P., Tamburini, E., Cubillo, A., Munoz, A., Guillen, C., Sanchez, G., Manzano, H., Navarro, V., Ales, I., Massuti, B., Dank, M., Bodoky, G., Kahan, Z., Horvath, Z., Gabrail, N., Ozer, H., Galanopoulos, C., Hauke, R., Raj, M., Harputluoglu, H., Sevinc, A., Goker, E., Coker, A., Yalcin, S., Ali, M., Ata, O., Tugba, I., Elkassas, M., Abdel, A., Wakid, I., Shamaa, S., El, N., Kohail, H., Makarem, J., Chehade, I., Farhat, F., Lopez, C., and Marin, M.
Subjects: Male, Gastroenterology, law.invention, 0302 clinical medicine, Randomized controlled trial, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Clinical endpoint, Treatment Failure, ComputingMilieux_MISCELLANEOUS, education.field_of_study, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Antibiotics, Antineoplastic, Liver Neoplasms, Middle Aged, Sorafenib, 3. Good health, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 030211 gastroenterology & hepatology, Female, medicine.drug, medicine.medical_specialty, Carcinoma, Hepatocellular, Neutropenia, Population, Antineoplastic Agents, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Carcinoma, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, education, Adverse effect, Aged, Hepatology, Dose-Response Relationship, Drug, business.industry, medicine.disease, Thrombocytopenia, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Doxorubicin, Asthenia, Nanoparticles, business
Abstract: Summary Background Cytotoxic chemotherapy is generally ineffective in patients with hepatocellular carcinoma. We assessed the intravenous perfusion of doxorubicin-loaded nanoparticles in patients with hepatocellular carcinoma in whom previous sorafenib therapy had failed. Methods We did a multicentre, open-label, randomised, controlled phase 3 trial at 70 sites in 11 countries. Patients with hepatocellular carcinoma with one or more previous systemic therapies, including sorafenib, were randomly assigned to receive 30 mg/m2 doxorubicin-loaded nanoparticles (30 mg/m2 group), 20 mg/m2 doxorubicin-loaded nanoparticles (20 mg/m2 group), or standard care using a computer-generated randomisation list prepared by the funder and stratified by geographic region. Patients in the experimental groups received perfusion of the drug every 4 weeks and those in the control group received any systemic anticancer therapy (except sorafenib) as per investigator decision. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in the population of patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov , number NCT01655693 . Findings Between June 15, 2012, and Jan 27, 2017, 541 patients were screened, of whom 144 were excluded and 397 were randomly assigned to one of the groups (133 to the 30 mg/m2 group; 130 to the 20 mg/m2 group; and 134 to the control group). Median follow-up was 22·7 months (IQR 11·2–34·9). After pooling the doxorubicin groups for the efficacy analysis, median overall survival was 9·1 months (95% CI 8·1–10·4) in the pooled doxorubicin-loaded nanoparticles group and 9·0 months (7·1–11·8) in the control group (HR 1·00 [95% CI 0·78–1·28], two-sided p=0·99). 227 (94%) of 242 patients who received doxorubicin-loaded nanoparticles and 100 (75%) of 134 patients in the control group had at least one treatment-emergent adverse event. The most common drug-related grade 3 or 4 treatment-emergent adverse events were neutropenia (25 [10%] of 242 treated with doxorubicin-loaded nanoparticles and eight [6%] of 134 in the control group), asthenia (six [2%] and four [3%]), and thrombocytopenia (three [1%] and ten [7%]). Six (2%) patients treated with doxorubicin-loaded nanoparticles and one (1%) of those in the control group were deemed by investigators to have had a drug-related death. Serious adverse events occurred in 74 (31%) patients who received doxorubicin-loaded nanoparticles and 48 (36%) in the control group. Interpretation Doxorubicin-loaded nanoparticles did not improve overall survival for patients with hepatocellular carcinoma in whom previous sorafenib treatment had failed. Funding Onxeo.
Published: 2019

21. Validation of Baveno VI Criteria for Screening and Surveillance of Esophageal Varices in Patients With Compensated Cirrhosis and a Sustained Response to Antiviral Therapy

Author: Dominique Thabut, Christophe Bureau, Richard Layese, Valérie Bourcier, Maryam Hammouche, Carole Cagnot, Patrick Marcellin, Dominique Guyader, Stanislas Pol, Dominique Larrey, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Jean-Pierre Zarski, Odile Goria, Paul Calès, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, Jean-Frédéric Blanc, Armand Abergel, Lawrence Serfaty, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Yannick Bacq, Claire Wartelle-Bladou, Thông Dao, Christophe Pilette, Christine Silvain, Christos Christidis, Dominique Capron, Brigitte Bernard-Chabert, Sophie Hillaire, Vincent Di Martino, Angela Sutton, Etienne Audureau, Françoise Roudot-Thoraval, Pierre Nahon, Hélène Fontaine, Vincent Leroy, Ghassan Riachi, Sebastien Dharancy, Claire Wartelle, Gérard Thiefin, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Toulouse [Toulouse], Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANRS France Recherche Nord & sud Sida-hiv hépatites, Hôpital Beaujon [AP-HP], CHU Pontchaillou [Rennes], Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Avicenne [AP-HP], Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Michallon, Hôpital Charles Nicolle [Rouen], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Saint-Joseph [Marseille], Hôpital Claude Huriez [Lille], CHU Lille, Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, CHU Saint-Antoine [AP-HP], INSERM U64 [AP-HP Hôpital Tenon], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Tenon [AP-HP], Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], CHU Trousseau [APHP], Centre Hospitalier d'Aix en Provence [Aix-en-Provence] (CHIAP ), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Le Mans (CH Le Mans), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Mutualiste de Montsouris (IMM), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Hôpital Robert Debré Paris, Hôpital Robert Debré, Hôpital Foch [Suresnes], Hôpital JeanMinjoz, Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Liver Cirrhosis, Male, 0301 basic medicine, Cirrhosis, Sustained Virologic Response, MESH: Sustained Virologic Response, MESH: Elasticity Imaging Techniques, medicine.disease_cause, Gastroenterology, Endoscopy, Gastrointestinal, 0302 clinical medicine, Esophageal varices, MESH: Practice Guidelines as Topic, Interquartile range, Mass Screening, MESH: Middle Aged, medicine.diagnostic_test, Portal Hypertension, Middle Aged, MESH: Endoscopy, Gastrointestinal, MESH: Hepatitis C, Chronic, Survival Rate, Population Surveillance, Hepatocellular carcinoma, Practice Guidelines as Topic, Disease Progression, Elasticity Imaging Techniques, Female, 030211 gastroenterology & hepatology, MESH: Disease Progression, Variceal Bleeding, MESH: Liver Cirrhosis, MESH: Antiviral Agents, medicine.medical_specialty, MESH: Survival Rate, MESH: Hepatitis B, Chronic, Hepatitis C virus, Esophageal and Gastric Varices, Antiviral Agents, MESH: Population Surveillance, 03 medical and health sciences, Elastometry, MESH: Esophageal and Gastric Varices, Hepatitis B, Chronic, Esophagus, Internal medicine, Hypertension, Portal, medicine, Humans, MESH: Mass Screening, MESH: Platelet Count, Hepatitis B virus, Prothrombin time, MESH: Hypertension, Portal, MESH: Humans, Hepatology, Platelet Count, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Chronic, medicine.disease, digestive system diseases, MESH: Male, 030104 developmental biology, business, Varices, MESH: Female
Abstract: International audience; Background & aims: Management of patients with cirrhosis includes endoscopic screening and surveillance to detect esophageal varices (EV) and prevent bleeding. However, the Baveno VI guidelines recommend avoiding endoscopies for patients with liver stiffness measurements below 20 kPa and platelet counts above 150,000 (favorable Baveno VI status) and endoscopic assessment of patients with higher levels of liver stiffness and platelet counts (unfavorable Baveno VI status). We aimed to validate the Baveno VI guidelines, evaluating outcomes of patients in the ANRS-CO12 CirVir cohort with compensated cirrhosis associated with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, with or without a sustained response to antiviral therapy.Methods: We performed an ancillary study using data from 891 patients in the ANRS CO12 CirVir cohort, treated at 35 centers in France, with HCV or HBV infection and biopsy-proven cirrhosis, Child-Pugh A scores, no previous complications, and no hepatocellular carcinoma who underwent an endoscopic procedure and had interpretable liver stiffness measurements and platelet counts. Progression of portal hypertension (PHT) was defined as the onset of varices needing treatment (VNT) or PHT-related bleeding. An sustained response to antiviral therapy was defined as undetectable level of HCV RNA by polymerase chain reaction assay (
Published: 2019

22. Impact of Non-alcoholic Fatty Liver Disease on long-term cardiovascular events and death in Chronic Obstructive Pulmonary Disease

Author: Ingrid Jullian-Desayes, Renaud Tamisier, Jean-Pierre Zarski, Sébastien Bailly, Marie Joyeux-Faure, Vincent Leroy, Maxime Maignan, Jean-Louis Pépin, Meriem Benmerad, Damien Viglino, Anais Plazanet, SALAS, Danielle, Hypoxie : Physiopathologie Respiratoire et Cardiovasculaire (HP2 ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), and Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, medicine.medical_specialty, lcsh:Medicine, Comorbidity, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Gastroenterology, Article, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Non-alcoholic Fatty Liver Disease, Risk Factors, Internal medicine, medicine, Humans, Prospective Studies, lcsh:Science, Prospective cohort study, Aged, Proportional Hazards Models, COPD, Univariate analysis, Multidisciplinary, Proportional hazards model, business.industry, Incidence, lcsh:R, Hazard ratio, Fatty liver, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Middle Aged, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cardiovascular Diseases, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, lcsh:Q, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, 030211 gastroenterology & hepatology, France, Steatosis, Steatohepatitis, business, Algorithms
Abstract: Chronic Obstructive Pulmonary Disease (COPD) and Non-Alcoholic Fatty Liver Disease (NAFLD) both independently increase cardiovascular risk. We hypothesized that NAFLD might increase the incidence of cardiovascular disease and death in COPD patients. The relationship between NAFLD, incident cardiovascular events, and death was assessed in a prospective cohort of COPD patients with 5-year follow-up. Noninvasive algorithms combining biological parameters (FibroMax®) were used to evaluate steatosis, non-alcoholic steatohepatitis (NASH) and liver fibrosis. Univariate and multivariate Cox regression models were used to assess the hazard for composite outcome at the endpoint (death or cardiovascular event) for each liver pathology. In 111 COPD patients, 75% exhibited liver damage with a prevalence of steatosis, NASH and fibrosis of 41%, 37% and 61%, respectively. During 5-year follow-up, 31 experienced at least one cardiovascular event and 7 died. In univariate analysis, patients with liver fibrosis had more cardiovascular events and higher mortality (Hazard ratio [95% CI]: 2.75 [1.26; 6.03]) than those with no fibrosis; this remained significant in multivariate analysis (Hazard ratio [95% CI]: 2.94 [1.18; 7.33]). We also found that steatosis and NASH were not associated with increased cardiovascular events or mortality. To conclude, early assessment of liver damage might participate to improve cardiovascular outcomes in COPD patients.
Published: 2018

23. Incidence of Hepatocellular Carcinoma After Direct Antiviral Therapy for HCV in Patients With Cirrhosis Included in Surveillance Programs

Author: Pierre Nahon, Richard Layese, Valérie Bourcier, Carole Cagnot, Patrick Marcellin, Dominique Guyader, Stanislas Pol, Dominique Larrey, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Jean-Pierre Zarski, Ghassan Riachi, Paul Calès, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, Jean-Frédéric Blanc, Armand Abergel, Lawrence Serfaty, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Yannick Bacq, Claire Wartelle, Thông Dao, Dominique Thabut, Christophe Pilette, Christine Silvain, Christos Christidis, Eric Nguyen-Khac, Brigitte Bernard-Chabert, David Zucman, Vincent Di Martino, Angela Sutton, Françoise Roudot-Thoraval, Etienne Audureau, Hélène Fontaine, Vincent Leroy, Sebastien Dharancy, Sophie Hillaire, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ANRS France Recherche Nord & sud Sida-hiv hépatites, Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'hépatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut Arnault Tzanck, Hospices Civils de Lyon (HCL), Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département d'hépato-gastroentérologie, CHU Grenoble-Université Grenoble Alpes (UGA), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Hôpital Claude Huriez [Lille], CHU Lille, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Tenon [AP-HP], Onxeo S.A., Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier d'Aix en Provence [Aix-en-Provence] (CHIAP ), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Le Mans (CH Le Mans), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hellenic Open University [Patras], Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Foch [Suresnes], Service d'Hépatologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ANRS, Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Nicolle [Rouen]-CHU Rouen, CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [APHP], Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], CHU Saint-Eloi, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre d'investigation de la fibrose hépatique [CHU de Bordeaux] (Hôpital Haut-Lévêque ), Hôpital Haut-Lévêque [CHU de Bordeaux], Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Grenoble Alpes (UGA)-CHU Grenoble, Hôpital Purpan [Toulouse], Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Service de médecine interne et maladies digestives [CHU Toulouse], SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), SIGMA Clermont, Hépatologie Gastro-Entérologie, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service d'hépatologie [CHU Saint-Antoine], UMR INSERM U955, École nationale vétérinaire d'Alfort (ENVA), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépato-gastroentérologie [CHU Amiens-Picardie], Service de Médecine Interne [Hôpital Foch, Suresnes] (SMI), Univ Angers, Okina, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP]
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Cirrhosis, [SDV]Life Sciences [q-bio], Gastroenterology, Antiviral Agents, Telaprevir, 03 medical and health sciences, 0302 clinical medicine, Liver neoplasms, Internal medicine, medicine, Humans, Aged, Proportional Hazards Models, Retrospective Studies, Hepatology, business.industry, Incidence, Carcinoma, Retrospective cohort study, Hepatocellular, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Middle Aged, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases, 3. Good health, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cohort, 030211 gastroenterology & hepatology, Female, Liver function, Interferons, business, Liver cancer, medicine.drug
Abstract: International audience; Background & aims - Retrospective studies have found an unexpectedly high incidence of hepatocellular carcinoma (HCC) among patients with hepatitis C virus (HCV)-associated cirrhosis who received direct-acting antiviral (DAA) agents. We analyzed data from the ANRS CO12 CirVir cohort to compare the incidence of HCC in patients with cirrhosis who received DAA therapy vs patients treated with interferon (IFN). Methods - Data were collected from 1270 patients with compensated biopsy-proven HCV-associated cirrhosis recruited from 2006 through 2012 at 35 centers in France. For descriptive purpose, patients were classified as follows: patients who received DAA treatment (DAA group, n = 336), patients who achieved a sustained virologic response (SVR) following an IFN-based regimen (SVR-IFN group, n = 495), or patients who never received DAA treatment and never had an SVR following IFN therapy (non-SVR group, n = 439). The patients were included in HCC surveillance programs based on ultrasound examination every 6 months, and clinical and biological data were recorded. To account for confounding by indication due to differences in patient characteristics at treatment initiation, we constructed a time-dependent Cox regression model weighted by the inverse probability of treatment and censoring (IPTCW) to assess the treatment effects of DAA on time until HCC. Results - Compared with patients in the SVR-IFN group, patients in the DAA group were older, higher proportions had diabetes or portal hypertension, and liver function was more severely impaired. The crude 3-year cumulative incidences of HCC were 5.9% in the DAA group, 3.1% in the SVR-IFN group, and 12.7% in the non-SVR group (overall P < .001; unadjusted hazard ratio [HR] for HCC 2.03; 95% confidence interval [CI] 1.07-3.84; P = .030 for the DAA group vs the SVR-IFN group). HCC characteristics were similar among groups. Among patients with HCC, the DAA group received less-frequent HCC screening than the other 2 groups (P = .002). After Cox analyses weighted by the IPTCW, we found no statistically significant increase in risk of HCC associated with DAA use (HR 0.89; 95% CI 0.46-1.73; P = .73). Conclusions - Analysis of data from the ANRS CO12 CirVir cohort reveals that the apparent increase in HCC incidence observed in patients with cirrhosis treated with DAAs compared with patients who achieved SVR following an IFN therapy can be explained by patient characteristics (age, diabetes, reduced liver function) and lower screening intensity.
Published: 2018

24. Impact of effective versus sham continuous positive airway pressure on liver injury in obstructive sleep apnoea: Data from randomized trials

Author: Jean-Pierre Zarski, Candice Trocme, Sandrine Launois-Rollinat, Ingrid Jullian-Desayes, Judith Aron-Wisnewsky, Jean-Louis Pépin, Renaud Tamisier, Marie Joyeux-Faure, and Patrick Levy
Subjects: Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, medicine.medical_treatment, Gastroenterology, law.invention, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Randomized controlled trial, Non-alcoholic Fatty Liver Disease, Risk Factors, law, Internal medicine, Humans, Medicine, Continuous positive airway pressure, Risk factor, Sleep Apnea, Obstructive, Continuous Positive Airway Pressure, business.industry, FibroTest, Fatty liver, Middle Aged, medicine.disease, nervous system diseases, respiratory tract diseases, Surgery, Treatment Outcome, 030228 respiratory system, Female, 030211 gastroenterology & hepatology, Steatohepatitis, Steatosis, business, Biomarkers
Abstract: Background and objective Obstructive sleep apnoea (OSA) could be an independent risk factor for non-alcoholic fatty liver disease (NAFLD) occurrence and progression. The impact of continuous positive airway pressure (CPAP) treatment on non-invasive markers of NAFLD has not been studied. The aim of this study was to evaluate the effect of 6–12 weeks of effective CPAP on the FibroMax test (comprising components including the SteatoTest, NashTest and FibroTest) through three randomized sham controlled studies. Methods The FibroMax test was performed in 103 obstructive sleep apnoea patients (apnoea + hypopnoea index > 15/h) enrolled in a randomized study comparing sham versus effective CPAP. Results At baseline, 40.4% of patients in the sham CPAP group and 45.5% in the CPAP group exhibited liver steatosis. Furthermore, 39.6% of patients in the sham CPAP group and 58.4% in the CPAP group displayed borderline or possible non-alcoholic steatohepatitis (NASH). Six to twelve weeks of effective CPAP did not demonstrate any impact on reducing steatosis, NASH or liver fibrosis even after adjustment for gender, BMI, baseline apnoea + hypopnoea index and severity of liver injury. Conclusion A number of non-invasive markers of liver damage are increased in untreated obstructive sleep apnoea patients, potentially contributing to cardiometabolic risk, but they do not improve after 6–12 weeks of effective CPAP treatment. Clinical trial registration: NCT01196845 (ADISAS), NCT00464659 (MneSAS) and NCT00669695 (StatinflaSAS) at ClinicalTrials.gov.
Published: 2015

25. Diagnostic performance of a new algorithm combining simple, non-invasive and inexpensive tests for predicting the presence of liver severe fibrosis and cirrhosis in patients with chronic hepatitis B

Author: Jean Nana, Skaare Kristina, Tarik Asselah, Adler Michael, Marie-Noëlle Hilleret, Vincent Leroy, Marlu Alice, Jean Luc Bosson, and Jean-Pierre Zarski
Subjects: Hepatology
Published: 2020

26. Impact of non-alcoholic fatty liver disease on late cardiovascular events and death in Chronic Obstructive Pulmonary Disease

Author: Anais Plazanet, Ingrid Jullian-Desayes, Marie Joyeux-Faure, Damien Viglino, Renaud Tamisier, Jean-Pierre Zarski, Jean-Louis Pépin, Maxime Maignan, Vincent Leroy, Meriem Benmerad, and Sébastien Bailly
Subjects: medicine.medical_specialty, business.industry, Internal medicine, Fatty liver, medicine, Pulmonary disease, Non alcoholic, Disease, medicine.disease, business, Gastroenterology
Published: 2018

27. Compliance With Hepatocellular Carcinoma Surveillance Guidelines Associated With Increased Lead-Time Adjusted Survival of Patients With Compensated Viral Cirrhosis: A Multi-Center Cohort Study

Author: Charlotte E. Costentin, Richard Layese, Valérie Bourcier, Carole Cagnot, Patrick Marcellin, Dominique Guyader, Stanislas Pol, Dominique Larrey, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Jean-Pierre Zarski, Ghassan Riachi, Paul Calès, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, Jean-Frédéric Blanc, Armand Abergel, Lawrence Serfaty, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Yannick Bacq, Claire Wartelle, Thông Dao, Dominique Thabut, Christophe Pilette, Christine Silvain, Christos Christidis, Eric Nguyen-khac, Brigitte Bernard-Chabert, David Zucman, Vincent Di Martino, Angela Sutton, Eric Letouzé, Sandrine Imbeaud, Jessica Zucman-Rossi, Etienne Audureau, Françoise Roudot-Thoraval, Pierre Nahon, Hélène Fontaine, Vincent Leroy, Sebastien Dharancy, Dominique Capron, Gérard Thiefin, Sophie Hillaire, CHU Henri Mondor, Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), ANRS France Recherche Nord & sud Sida-hiv hépatites, Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'hépatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], CHU Saint-Eloi-Université de Montpellier (UM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut Arnault Tzanck, Hospices Civils de Lyon (HCL), Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département d'hépato-gastroentérologie, CHU Grenoble-Université Grenoble Alpes (UGA), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), CHU Toulouse [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Hôpital Claude Huriez [Lille], CHU Lille, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], UMR INSERM U955, École nationale vétérinaire - Alfort (ENVA), Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Tenon [AP-HP], Onxeo S.A., Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], CHU Trousseau [APHP], Centre Hospitalier d'Aix en Provence [Aix-en-Provence] (CHIAP ), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Le Mans (CH Le Mans), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hellenic Open University [Patras], Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Foch [Suresnes], Service d'Hépatologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Université Paris 13 (UP13), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor [Créteil], Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], CHU Saint-Eloi, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre d'investigation de la fibrose hépatique [CHU de Bordeaux] (Hôpital Haut-Lévêque ), Hôpital Haut-Lévêque [CHU de Bordeaux], Université Nice Sophia Antipolis (... - 2019) (UNS), Hôpital Purpan [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), SIGMA Clermont, Hépatologie Gastro-Entérologie, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service d'hépatologie [CHU Saint-Antoine], Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), École nationale vétérinaire d'Alfort (ENVA), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépato-gastroentérologie [CHU Amiens-Picardie], Service de Médecine Interne [Hôpital Foch, Suresnes] (SMI), Labex Immuno-oncology, Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Grenoble Alpes (UGA)-CHU Grenoble, Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP]
Subjects: Male, Liver Cirrhosis, medicine.medical_specialty, Carcinoma, Hepatocellular, [SDV]Life Sciences [q-bio], Hepacivirus, Kaplan-Meier Estimate, Antiviral Agents, 03 medical and health sciences, 0302 clinical medicine, Liver neoplasms, Internal medicine, Medicine, Humans, Prospective Studies, Prospective cohort study, Early Detection of Cancer, Aged, Hepatology, business.industry, Hazard ratio, Carcinoma, Gastroenterology, Hepatocellular, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Hepatitis B, Middle Aged, medicine.disease, 3. Good health, Transplantation, Liver, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Practice Guidelines as Topic, Multivariate Analysis, 030211 gastroenterology & hepatology, Female, Guideline Adherence, France, business, Liver cancer, Viral hepatitis, hepatitis B virus, Follow-Up Studies
Abstract: International audience; Background & aims - Semi-annual surveillance for hepatocellular carcinoma (HCC) is recommended for patients with cirrhosis. We aimed to determine how compliance with HCC surveillance guidelines affects survival times of patients with hepatitis C virus- or hepatitis B virus-associated compensated cirrhosis who developed HCC. Methods - We collected data from the prospective ANRS CO12 CirVir study, from March 2006 through June 2012, on 1671 patients with biopsy-proven viral cirrhosis and no previous liver complications who were undergoing surveillance for HCC at 35 centers in France. Only 216 patients who developed HCC during the follow-up period were included in the analysis. Patients were considered to be compliant with surveillance guidelines if the time between their last surveillance image evaluation and diagnosis of HCC were fewer than 7 months and noncompliant if this time was 7 months or longer. Results - HCC was detected in 216 patients, at a median follow-up time of 59.7 months. Of these patients, 140 (80.5%) were Barcelona Clinic Liver Cancer stage 0/A, 135 (69.9%) received first-line curative treatment (15 underwent transplantation, 29 underwent resection, 89 received percutaneous ablation, and 2 received resection and percutaneous ablation), and 129 (60.0%) were compliant with surveillance guidelines. Seventy-nine of the patients with HCC died; 49 deaths were associated with tumor progression. After lead-time adjustment, overall survival (OS) time was longer in patients compliant with surveillance guidelines (median OS time, 53.2 months) than noncompliant patients (median OS time, 25.4 months) (P = .0107); this difference remained significant even when we changed lead time assumptions. In multivariate analysis adjusted for a propensity score, compliance with HCC surveillance guidelines was associated with low tumor burden, allocation of curative treatment, and increased OS time compared with noncompliance (hazard ratio for OS, 2.19; 95% confidence interval, 1.16-4.14; P = .0150). Conclusions - In an analysis of data from the ANRS CO12 CirVir cohort, we associated compliance with HCC surveillance guidelines (fewer than 7 months between image evaluations) with early diagnosis, allocation of curative treatment, and longer adjusted OS of patients with hepatitis C virus- or hepatitis B virus-associated compensated cirrhosis and a diagnosis of HCC.
Published: 2018

28. A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis

Author: Jean-Pierre Zarski, Raoul Poupon, Christine Silvain, Victor de Ledinghen, Dominique Rainteau, Sylvie Chollet-Martin, Fabien Zoulim, Odile Goria, Armand Abergel, Gisèle N'Kontchou, Pascal Potier, François Habersetzer, Guillaume Lefèvre, Anne Minello, Farid Gaouar, Olivier Roux, Eric Nguyen-Khac, Olivier Chazouillères, Jérôme Boursier, Lydie Humbert, Jean-Pierre Bronowicki, Isabelle Ollivier-Hourmand, Sara Lemoinne, Maryline Debette-Gratien, Dominique Larrey, Christophe Corpechot, Luc de Chaisemartin, Philippe Mathurin, Alexandra Rousseau, Alexandra Heurgué-Berlot, Farid-Hakeem Admane, Tabassome Simon, Antonia Le Gruyer, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Référence des Maladies Rares - Maladies Inflammatoires des Voies Biliaires et Service d’Hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche Clinique de l’Est Parisien [CHU Saint-Antoine] (URC-EST), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire [Rennes], Hôpital Claude Huriez [Lille], CHU Lille, CHU Rouen, Normandie Université (NU), Service d'hépato-gastro-entérologie et oncologie digestive [CHR Orléans], Centre Hospitalier Régional d'Orléans (CHRO), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nancy (CHU Nancy), Service d’Hépato-Gastroentérologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Service d'hépato-gastro-entérologie [CHU Haut-Lévêque], Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Hôpital Robert Debré, Service d'Hépato-gastroentérologie, 51092 Reims, France, affiliation inconnue, Service d'Hépato-gastroentérologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'hépato-gastroentérologie [CHU Grenoble Alpes], Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Sud - Paris 11 (UP11), Laboratoire des biomolécules (LBM UMR 7203), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Immunologie 'Autoimmunité et Hypersensibilités' [AP-HP Hôpital Bichat, Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], and Sorbonne Université (SU)
Subjects: Liver Cirrhosis, Male, Cirrhosis, Cholangitis, Biliary/complications/drug therapy, Obeticholic Acid, Placebo-controlled study, Gastroenterology, Placebos, chemistry.chemical_compound, Liver disease, 0302 clinical medicine, Treatment Failure, Bezafibrate/adverse effects/*therapeutic use, Multicenter, Hypolipidemic Agents/adverse effects/*therapeutic use, Hypolipidemic Agents, Combination Therapy, medicine.diagnostic_test, Liver Cirrhosis, Biliary, Ursodeoxycholic Acid, Obeticholic acid, General Medicine, Middle Aged, Prognosis, Ursodeoxycholic acid, 3. Good health, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, medicine.drug, Adult, medicine.medical_specialty, Outcomes, Placebo, Biochemical Response, Bile Acids and Salts, 03 medical and health sciences, Double-Blind Method, Internal medicine, medicine, Cholangitis/*drug therapy/etiology, Humans, Placebos/therapeutic use, Prothrombin time, Bezafibrate, business.industry, Ursodeoxycholic Acid/therapeutic use, medicine.disease, Renal-Function, Bile Acids and Salts/blood, chemistry, Fenofibrate Therapy, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: IF 79.258 (2017); International audience; Background : Patients with primary biliary cholangitis who have an inadequate response to therapy with ursodeoxycholic acid are at high risk for disease progression. Fibrates, which are agonists of peroxisome proliferator–activated receptors, in combination with ursodeoxycholic acid, have shown potential benefit in patients with this condition.Methods : In this 24-month, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 100 patients who had had an inadequate response to ursodeoxycholic acid according to the Paris 2 criteria to receive bezafibrate at a daily dose of 400 mg (50 patients), or placebo (50 patients), in addition to continued treatment with ursodeoxycholic acid. The primary outcome was a complete biochemical response, which was defined as normal levels of total bilirubin, alkaline phosphatase, aminotransferases, and albumin, as well as a normal prothrombin index (a derived measure of prothrombin time), at 24 months.Results : The primary outcome occurred in 31% of the patients assigned to bezafibrate and in 0% assigned to placebo (difference, 31 percentage points; 95% confidence interval, 10 to 50; P
Published: 2018

29. Ultradeep Pyrosequencing of NS3 To Predict Response to Triple Therapy with Protease Inhibitors in Previously Treated Chronic Hepatitis C Patients

Author: Olivier François, Katia Fusillier, Michael G. B. Blum, Jean-Pierre Zarski, Sylvie Larrat, Pauline Tremeaux, Patrice Morand, Réjane Beugnot, Alice Marlu, Jean-Baptiste Claude, Agnès Plages, Om Kulkarni, Anne Signori-Schmuck, Julien Lupo, Hervé Duborjal, Vincent Leroy, Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Centre National de la Recherche Scientifique (CNRS)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Université Joseph Fourier - Grenoble 1 (UJF), Biologie Computationnelle et Mathématique (TIMC-IMAG-BCM), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Genostar, GENOME Express (GENOME Express), GENOME Express, Earth and Environmental, AMEC, Biochimie et Génétique Moléculaire, CHU Grenoble-Hôpital Michallon, Pôle Digidune, Pôle DigiDune, Unité de Biophysique, CRSSA, Département d'hépato-gastroentérologie, Université Grenoble Alpes (UGA)-CHU Grenoble, Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), CHU Grenoble-Université Grenoble Alpes (UGA), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, and Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Microbiology (medical), NS3, medicine.medical_specialty, Entropy, medicine.medical_treatment, Mutation, Missense, Salvage therapy, Viral quasispecies, Viral Nonstructural Proteins, Biology, Antiviral Agents, Peripheral blood mononuclear cell, Gastroenterology, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Virology, Internal medicine, Drug Resistance, Viral, Genotype, medicine, Humans, Protease Inhibitors, Aged, 030304 developmental biology, Aged, 80 and over, Salvage Therapy, 0303 health sciences, Protease, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Genetic Variation, High-Throughput Nucleotide Sequencing, virus diseases, Odds ratio, Hepatitis C, Chronic, Middle Aged, Prognosis, digestive system diseases, Confidence interval, 3. Good health, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], HCV, Immunology, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology
Abstract: Despite the gain in sustained virological responses (SVR) provided by protease inhibitors (PIs), failures still occur. The aim of this study was to determine if a baseline analysis of the NS3 region using ultradeep pyrosequencing (UDPS) can help to predict an SVR. Serum samples from 40 patients with previously nonresponding genotype 1 chronic hepatitis C who were retreated with triple therapy, including a PI, were analyzed. Baseline UDPS of the NS3 gene was performed on plasma and peripheral blood mononuclear cells (PBMC). Mutations conferring resistance to PIs were sought. The overall diversity of the quasispecies was evaluated by calculating the Shannon entropy (SE). Resistance mutations were found in plasma and PBMC but were not discriminating enough to predict an SVR. NS3 quasispecies heterogeneity was significantly lower at baseline in patients achieving an SVR than in those not achieving an SVR (SE of 26.98 ±16.64 x10^3 versus 44.93 ±19.58 x10^3, P =0.0047). With multivariate analysis, the independent predictors of an SVR were fibrosis of stage F <2 (odds ratio [OR], 13.3; 95% confidence interval [CI], 1.25 to 141.096; P < 0.03) and SE below the median (OR, 5.4; 95% CI, 1.22 to 23.87; P < 0.03). More than the presence of minor mutations at the baseline in plasma or in PBMC, the NS3 viral heterogeneity determined by UDPS is an independent factor for an SVR in previously treated patients receiving triple therapy that includes a PI.&nbsp
Published: 2015

30. Safety and efficacy of intra-arterial hepatic chemotherapy with doxorubicin-loaded nanoparticles in hepatocellular carcinoma

Author: Julien Taieb, Georges Philippe Pageaux, Bérangère Vasseur, Gilles verset, Armand Abergel, Claude Masliah, Pierre Attali, Jean-Pierre Bronowicki, Mohamed Bouattour, Michel Doffoel, Si-Nafa Si-Ahmed, Philippe Merle, Jean-Pierre Zarski, Laetitia Farloux, Patrice Couzigou, Gilles Pelletier, Philippe Camus, Etienne Dorval, Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service des maladies respiratoires [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôtel-Dieu de Nantes, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Michallon, Hôpital Paul Brousse, Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Centre Hospitalier Régional d'Orléans (CHRO), Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Strasbourg, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service de gastroenterologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Onxeo S.A., SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), and roussel, pascale
Subjects: Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Aucun, [SDV.CAN]Life Sciences [q-bio]/Cancer, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Gastroenterology, doxorubicin, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Clinical endpoint, Doxorubicin, 030212 general & internal medicine, Dosing, Respiratory system, Original Research, Chemotherapy, therapy, Respiratory distress, business.industry, nanoparticle, Généralités, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, hepatocellular carcinoma, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Surgery, Regimen, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business, medicine.drug
Abstract: Background Doxorubicin Transdrug (DT), a nanoformulation of doxorubicin, was demonstrated to overcome the chemoresistance of hepatocellular carcinoma (HCC) in preclinical models. Its efficacy and safety were thus investigated in phase I and randomised phase II trials in unresectable HCC. Patients and methods Phase I was a single dose of DT through the hepatic intra-arterial (HIA) route, dose-escalating 3+3 trial, evaluating five-dose levels from 10 to 40 mg/m 2 with maximal tolerated dose (MTD) as primary endpoint. The multicentre phase II trial randomly assigned (2:1 ratio) patients to receive either 30 mg/m 2 of DT through HIA route every 4 weeks for up to three courses or best standard of care (BSC). Progression-free survival (PFS) rate at 3 months was the primary endpoint. Overall survival (OS) and disease control rate (DCR) were secondary endpoints. Results In phase I, haematological and respiratory limited toxicities were reported at 35 and 40 mg/m 2, giving MTD at 30 mg/m 2. Partial response rate was 10%, and stable disease 70%. Phase II was discontinued due to three severe acute respiratory distress events in the DT group while 17 patients had received 30 mg/m 2 DT and 11 BSC. At 3 months, PFS was 64% (95% CI 31 to 89) vs 75% (95% CI 35 to 97), and DCR 35% vs 27% in DT and BSC, respectively (p=NS). Median OS was 32.6 months (95% CI 8.2 to 34.1) in DT group and 15 months (95% CI 8.0 to 18.8) in BSC group (p, SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2017

31. Estimate of hepatocellular carcinoma incidence in patients with alcoholic cirrhosis

Author: Jean-Marie Péron, Jean-Pierre Zarski, Perarnau Jm, Albert Tran, Dominique Roulot, Isabelle Archambeaud, Xavier Amiot, Nicolas Carbonell, Odile Goria, Cendrine Chaffaut, Frédéric Oberti, Eric Nguyen-Khac, Violaine Ozenne, Alexandre Louvet, Stanislas Pol, Gabriel Perlemuter, Sylvie Chevret, Thong Dao, Christophe Moreno, Nathalie Ganne-Carrié, Jean Henrion, Valérie Bourcier, Teresa Antonini, Michel Beaugrand, Victor de Lédinghen, Romain Moirand, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13), Université Sorbonne Paris Cité (USPC), Ligue Nationale Contre le Cancer - Paris, Ligue Nationale Contre le Cancer (LNCC), Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), Université Paris Diderot - Paris 7 (UPD7)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Unité d'Hématologie [Bruxelles, Belgium] (CUB Hôpital Erasme), Université libre de Bruxelles (ULB)-CUB Hôpital Erasme [Bruxelles, Belgium], Unité d'Hématologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), CHU Amiens-Picardie, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Paul Brousse, Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Département d'hépatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Lariboisière-Fernand-Widal [APHP], Unité d'Hématologie [CH de Jolimont-Lobbes, Belgium], Centre Hospitalier de Jolimont-Lobbes [Haine Saint-Paul, Belgium], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), AP-HP - Hôpital Antoine Béclère [Clamart], CHU Tenon [AP-HP], CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, The promoter of the study was the Assistance Publique des Hôpitaux de Paris (APHP), and the cohort was funded by the Institut National du Cancer (INCa) and the French Association for Research in Cancer and the National Agency for Research on HIV and Hepatitis., Jonchère, Laurent, Université Fédérale Toulouse Midi-Pyrénées, Ligue Nationnale Contre le Cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université Libre de Bruxelles [Bruxelles] (ULB)-CUB Hôpital Erasme [Bruxelles, Belgium], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [APHP], CHU Cochin [AP-HP]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Cochin [AP-HP], Hôpital Lariboisière, Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Antoine Béclère, CHU Tenon [APHP], Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: Male, Alcoholic liver disease, Cirrhosis, Biopsy, Gastroenterology, Liver disease, 0302 clinical medicine, Liver Cirrhosis, Alcoholic, Risk Factors, Gastro-entérologie, Prospective Studies, HCC, Prospective cohort study, education.field_of_study, Mortality rate, Incidence (epidemiology), Incidence, Liver Neoplasms, Age Factors, Middle Aged, Progression-Free Survival, 3. Good health, Liver, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Prothrombin, alpha-Fetoproteins, medicine.medical_specialty, Carcinoma, Hepatocellular, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Milan criteria, 03 medical and health sciences, Competing risk analysis, Sex Factors, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, education, Aged, Hepatology, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Bilirubin, medicine.disease, digestive system diseases, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Multivariate Analysis, Compensated cirrhosis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Follow-Up Studies
Abstract: Background & Aims: More than 90% of cases of hepatocellular carcinoma (HCC) occur in patients with cirrhosis, of which alcohol is a major cause. The CIRRAL cohort aimed to assess the burden of complications in patients with alcoholic cirrhosis, particularly the occurrence of HCC. Methods: Patients with biopsy-proven compensated alcoholic cirrhosis were included then prospectively followed. The main endpoint was the incidence of HCC. Secondary outcomes were incidence of hepatic focal lesions, overall survival (OS), liver-related mortality and event-free survival (EFS). Results: From October 2010 to April 2016, 652 patients were included in 22 French and Belgian centers. During follow-up (median 29 months), HCC was diagnosed in 43 patients. With the limitation derived from the uncertainty of consecutive patients’ inclusion and from a sizable proportion of dropouts (153/652), the incidence of HCC was 2.9 per 100 patient-years, and one- and two-year cumulative incidences of 1.8% and 5.2%, respectively. Although HCC fulfilled the Milan criteria in 33 cases (77%), only 24 patients (56%) underwent curative treatment. An explorative prognostic analysis showed that age, male gender, baseline alpha-fetoprotein, bilirubin and prothrombin were significantly associated with the risk of HCC occurrence. Among 73 deaths, 61 had a recorded cause and 27 were directly attributable to liver disease. At two years, OS, EFS and cumulative incidences of liver-related deaths were 93% (95% CI 90.5–95.4), 80.3% (95% CI 76.9–83.9), and 3.2% (95% CI 1.6–4.8) respectively. Conclusion: This large prospective cohort incompletely representative of the whole population with alcoholic cirrhosis showed: a) an annual incidence of HCC of up to 2.9 per 100 patient-years, suggesting that surveillance might be cost effective in these patients; b) a high proportion of HCC detected within the Milan criteria, but only one-half of detected HCC cases were referred for curative treatments; c) a two-year mortality rate of up to 7%. Lay summary: Cirrhosis is a risk factor for primary liver cancer, leading to recommendations for periodic screening. However, for alcohol-related liver disease the rational of periodic screening for hepatocellular carcinoma (HCC) is controversial, as registry and databased studies have suggested a low incidence of HCC in these patients and highly competitive mortality rates. In this study, a large cohort of patients with biopsy-proven alcoholic cirrhosis prospectively screened for HCC demonstrated a high annual incidence of HCC (2.9%) and a high percentage of small cancers theoretically eligible for curative treatment. This suggests that patients with liver disease related to alcohol should not be ruled out of screening., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2017

32. Eradication of Hepatitis C Virus Infection in Patients With Cirrhosis Reduces Risk of Liver and Non-Liver Complications

Author: Pierre Nahon, Valérie Bourcier, Richard Layese, Etienne Audureau, Carole Cagnot, Patrick Marcellin, Dominique Guyader, Hélène Fontaine, Dominique Larrey, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Jean-Pierre Zarski, Vincent Leroy, Ghassan Riachi, Paul Calès, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, Sébastien Dharancy, Jean-Frédéric Blanc, Armand Abergel, Lawrence Serfaty, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Yannick Bacq, Claire Wartelle, Thông Dao, Yves Benhamou, Christophe Pilette, Christine Silvain, Christos Christidis, Dominique Capron, Brigitte Bernard-Chabert, David Zucman, Vincent Di Martino, Vincent Thibaut, Dominique Salmon, Marianne Ziol, Angela Sutton, Stanislas Pol, Françoise Roudot-Thoraval, Gérard Thiefin, Sophie Hillaire, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Cochin [AP-HP], Cellules souches normales et cancéreuses, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Arnault Tzanck, Hospices Civils de Lyon (HCL), Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département d'hépato-gastroentérologie, CHU Grenoble-Université Grenoble Alpes (UGA), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), ScaLable Information Discovery and Exploitation [Grenoble] (SLIDE), Laboratoire d'Informatique de Grenoble (LIG ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), CHU Toulouse [Toulouse], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Hôpital Saint-Joseph [Marseille], Hôpital Claude Huriez [Lille], CHU Lille, Hôpital Saint-André, Hôpital Hôtel-Dieu de Clermont-Ferrand, CHU Clermont-Ferrand, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hépato-gastro-entérologie [APHP Henri Mondor], CHU Tenon [AP-HP], Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Service de gastro-entérologie [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre Hospitalier d'Aix en Provence [Aix-en-Provence] (CHIAP ), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Mobilités : Vieillissement, Pathologie, Santé (COMETE), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Le Mans (CH Le Mans), Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Mutualiste de Montsouris (IMM), CHU Amiens-Picardie, Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Foch [Suresnes], Service d'hépatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Pontchaillou [Rennes], Université Paris Descartes - Paris 5 (UPD5), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Service Maladies infectieuses et tropicales [AP-HP Hôpital Cochin], Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépatologie médicale [CHU Cochin], Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de santé publique [Mondor], Service d'Hépato-gastroentérologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Hôpital Henri Mondor, Assistance Publique - Hôpitaux de Paris (AP-HP), Department of hepatology, CHU Saint-Eloi, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre de Recherche sur le Cancer de Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Hôpital Purpan [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Service d'hépato-gastro-entérologie, Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital Huriez-Université de Lille, Hôpital Claude Hurriez, Inserm, UMR-1053, Université de Bordeaux, Bordeaux, F-33076, France, Centre hospitalier universitaire de Bordeaux, Department of Hepatology, Hôpital Saint-André, Bordeaux, F-33076, France, Service d'Hépato-Gastro-Entérologie, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Hopital d'Aix en Provence, Service d'Hépatogastroentérologie, Service de Médecine Interne (Med Int - Hôpital Foch), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), FHDH-ANRS CO4, Service d'anatomie pathologique, Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Jean Verdier, Génomique Fonctionnelle des Tumeurs Solides ( U1162 ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Beaujon, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Cochin [AP-HP], Université Montpellier 1 ( UM1 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Centre méditérannéen de médecine moléculaire ( C3M ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Université de Lorraine ( UL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), ScaLable Information Discovery and Exploitation [Saint Martin d’Hères] ( SLIDE ), Laboratoire d'Informatique de Grenoble ( LIG ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National Polytechnique de Grenoble ( INPG ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National Polytechnique de Grenoble ( INPG ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Service d'Hépato-Gastroentérologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques ( HIFIH ), Université d'Angers ( UA ), Hepato-gastro-enterology, Toulouse University hospital, Institut de Recherche en Santé Digestive - IRSD [Purpan, Toulouse], Institut National de la Recherche Agronomique ( INRA ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse ( ENVT ), Institut National Polytechnique de Toulouse ( INPT ) -Institut National Polytechnique de Toulouse ( INPT ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Assistance Publique - Hôpitaux de Marseille ( APHM ), CHU Saint-Antoine [APHP], Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse, Service de gastro-entérologie, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Service d'Hépato-Gastro-Enterologie et Nutrition [Caen], Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -CHU Caen, Mobilités : Vieillissement, Pathologie, Santé ( COMETE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Caen Normandie ( UNICAEN ), Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Service de Médecine Interne ( Med Int - Hôpital Foch ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Université Paris Descartes - Paris 5 ( UPD5 ), CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Hôpital Jean Verdier AP-HP Bondy, Hôpital Jean Verdier, Laboratoire de Recherche Vasculaire Translationnelle ( LVTS ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Charles Nicolle [Rouen], CHU Rouen, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), CHU Trousseau [APHP], Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Grenoble Alpes (UGA)-CHU Grenoble, Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)
Subjects: 0301 basic medicine, Liver Cirrhosis, Male, Cirrhosis, Sustained Virologic Response, Direct Antivirals, Gastroenterology, Body Mass Index, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Prospective Studies, Prospective cohort study, Metabolic Syndrome, education.field_of_study, Incidence, Hazard ratio, Liver Neoplasms, virus diseases, Hepatitis C, Bacterial Infections, gamma-Glutamyltransferase, Middle Aged, Prognosis, 3. Good health, ANRS CirVir, Cardiovascular Diseases, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Female, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, France, medicine.medical_specialty, Carcinoma, Hepatocellular, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Lower risk, Antiviral Agents, 03 medical and health sciences, Spontaneous bacterial peritonitis, Internal medicine, medicine, Diabetes Mellitus, Humans, Aspartate Aminotransferases, education, Aged, Dyslipidemias, Hepatology, business.industry, Platelet Count, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, digestive system diseases, Surgery, 030104 developmental biology, Prothrombin Time, business, HCV Clearance, Follow-Up Studies
Abstract: International audience; BACKGROUND & AIMS: We performed a prospective study to investigate the effects of a sustained viral response (SVR) on outcomes of patients with hepatitis C virus (HCV) infection and compensated cirrhosis. METHODS: We collected data from 1323 patients included in the prospective Agence Nationale pour la Recherche sur le SIDA et les hépatites virales (ANRS) viral cirrhosis (CirVir) cohort, recruited from 35 clinical centers in France from 2006 through 2012. All patients had HCV infection and biopsy-proven cirrhosis, were Child-Pugh class A, and had no prior liver complications. All patients received anti-HCV treatment before or after inclusion (with interferon then with direct antiviral agents) and underwent an ultrasound examination every 6 months, as well as endoscopic evaluations. SVR was considered as a time-dependent covariate; its effect on outcome was assessed by the Cox proportional hazard regression method. We used a propensity score to minimize confounding by indication of treatment and capacity to achieve SVR. RESULTS: After a median follow-up period of 58.2 months, 668 patients (50.5%) achieved SVR. SVR was associated with a decreased incidence of hepatocellular carcinoma (hazard ratio [HR] compared with patients without an SVR, 0.29; 95% confidence interval [CI], 0.19-0.43; P < .001) and hepatic decompensation (HR, 0.26; 95% CI, 0.17-0.39; P < .001). Patients with SVRs also had a lower risk of cardiovascular events (HR, 0.42; 95% CI, 0.25-0.69; P = .001) and bacterial infections (HR, 0.44; 95% CI, 0.29-0.68; P < .001). Metabolic features were associated with a higher risk of hepatocellular carcinoma in patients with SVRs, but not in patients with viremia. SVR affected overall mortality (HR, 0.27 compared with patients without SVR; 95% CI, 0.18-0.42; P < .001) and death from liver-related and non-liver-related causes. Similar results were obtained in a propensity score-matched population. CONCLUSIONS: We confirmed a reduction in critical events, liver-related or not, in a prospective study of patients with HCV infection and compensated cirrhosis included in the CirVir cohort who achieved an SVR. We found an SVR to reduce overall mortality and risk of death from liver-related and non-liver-related causes. A longer follow-up evaluation is required to accurately describe and assess specific risk factors for complications in this population.
Published: 2017

33. Safety and efficacy of daclatasvir-sofosbuvir in HCV genotype 1-mono-infected patients

Author: Dominique Thabut, Eric Billaud, Alpha Diallo, Sandy Lucier, Valérie Bourcier, Christophe Hézode, Fabien Zoulim, Isabelle Rosa, François Habersetzer, Patrick Marcellin, Ghassan Riachi, Anne Minello, Jérôme Gournay, Jean-Pierre Bronowicki, Eric Saillard, Claire Geist, Hélène Fontaine, Isabelle Fouchard-Hubert, Céline Dorival, Marc Bourlière, Dominique Larrey, Dominique Guyader, Sophie Metivier, Louis d’Alteroche, Albert Tran, Laurent Alric, Fabrice Carrat, Xavier Causse, Didier Samuel, Philippe Mathurin, Stanislas Pol, Victor de Ledinghen, Jean-Pierre Zarski, Olivier Chazouillères, Ventzislava Petrov-Sanchez, Véronique Loustaud-Ratti, Service d'hépatologie médicale [CHU Cochin], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Service d'hépato-gastro-entérologie, Assistance Publique - Hôpitaux de Marseille ( APHM ), Hôpital Saint-Joseph [Marseille], Département de la recherche clinique et du développement, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Hôtel-Dieu-Unité de Recherche Clinique en Economie de la santé d'Ile de France (URC Eco), Institut Pierre Louis d'Epidémiologie et de Santé Publique ( iPLESP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), AP HP, Departement Gastroenterologie, Centre Hospitalier Universitaire Henri Mondor, CHU Saint-Eloi, Cellules souches normales et cancéreuses, Université Montpellier 1 ( UM1 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Université de Lorraine ( UL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche sur le Cancer de Lyon, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre méditérannéen de médecine moléculaire ( C3M ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Gastro-entérologie - Hépatologie [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Département d'hépato-gastroentérologie, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AP-HP Hôpital Paul Brousse, Centre hépato-biliaire - CHB [Paul Brousse, Paris], Université Paris-Sud - Paris 11 ( UP11 ) -AP-HP Hôpital Paul Brousse, Foie, métabolismes et cancer, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon, Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Institut de Recherche en Santé Digestive - IRSD [Purpan, Toulouse], Institut National de la Recherche Agronomique ( INRA ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse ( ENVT ), Institut National Polytechnique de Toulouse ( INPT ) -Institut National Polytechnique de Toulouse ( INPT ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Service d'hépatologie [Saint-Antoine], CHU Saint-Antoine [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP)-Université Pierre et Marie Curie - Paris 6 ( UPMC ), Service d'Hépato-Gastroentérologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Service d'Hépato-gastroentérologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Jean Verdier, Hôpital Huriez-Université de Lille, Pharmacologie des Immunosuppresseurs et de la Transplantation ( PIST ), Université de Limoges ( UNILIM ) -CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, CHU Trousseau [Tours], CHRU Tours, Centre Hospitalier Universitaire d'Angers ( CHU Angers ), PRES Université Nantes Angers Le Mans ( UNAM ), Laboratoire HIFIH, Université d'Angers ( UA ), Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut de Virologie, Hépato-gastro-entérologie et oncologie digestive, Centre Hospitalier Régional d'Orléans ( CHR ), Centre hospitalier régional Metz-Thionville ( CHR Metz-Thionville ), CHI Créteil, Hôpital Hôtel-Dieu [Paris]-Centre hospitalier universitaire de Nantes ( CHU Nantes ), CHU Pointe-à-Pitre/Abymes [Guadeloupe], Service des maladies infectieuses [Nantes], Recherches fondamentales, cliniques et thérapeutiques sur les hépatites virales, ANRS, INSERM-ANRS (France REcherche Nord&sud Sida-vih Hépatites), France, ANR (Agence Nationale de la Recherche), France, DGS (Direction Générale de la Santé), France and MSD, United States, Janssen, United States, Gilead, United States, Abbvie, United States, BMS, United States, Roche, Switzerland., Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nutrition et cerveau (U1213, U855), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Grenoble-Université Grenoble Alpes (UGA), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Beaujon [AP-HP], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Service d'hépatologie [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, Centre Hospitalier Régional d'Orléans (CHRO), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Hospitalier Intercommunal de Créteil (CHIC), Hôtel-Dieu de Nantes, Centre hospitalier universitaire de Nantes (CHU Nantes), Service des maladies infectieuses et tropicales [CHU Nantes], ANRS France Recherche Nord & sud Sida-hiv hépatites, Jonchère, Laurent, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance Publique - Hôpitaux de Marseille (APHM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Unité de Recherche Clinique en Economie de la santé d'Ile de France (URC Eco), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, Service Hépato-gastro-entérologie et oncologie digestive [CHR Orléans], Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université Grenoble Alpes (UGA)-CHU Grenoble, Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Paul Brousse-Université Paris-Sud - Paris 11 (UP11), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Charles Nicolle [Rouen]-CHU Rouen, CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Hôtel-Dieu-Unité de Recherche Clinique en Economie de la santé d'Ile de France (URC Eco), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-AP-HP Hôpital Paul Brousse, Institut de Recherche en Santé Digestive (IRSD ), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Saint-Antoine [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen]-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Hospitalier Régional d'Orléans (CHR), and Hôpital Hôtel-Dieu [Paris]-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: Male, Pyrrolidines, Sofosbuvir, Sustained Virologic Response, Hepacivirus, Direct antiviral agents, medicine.disease_cause, Chronic hepatitis C, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, 030212 general & internal medicine, biology, Imidazoles, Valine, Hepatitis B, Middle Aged, Genotype 1, 3. Good health, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Treatment Outcome, Cirrhosis, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Cohort, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, RNA, Viral, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, France, medicine.drug, medicine.medical_specialty, Daclatasvir, Hepatitis C virus, Antiviral Agents, Severe fibrosis, 03 medical and health sciences, Internal medicine, Ribavirin, Hepather cohort, Humans, Aged, Hepatology, business.industry, [ SDV.SP.PHARMA ] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Chronic, medicine.disease, biology.organism_classification, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Treatment, Regimen, chemistry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Carbamates, business
Abstract: International audience; Background & aims - We report the first real-life results of the sofosbuvir+daclatasvir combination in hepatitis C virus (HCV) genotype 1 infected patients. Methods - The France REcherche Nord&Sud Sida-hiv Hépatites (ANRS) CO22 HEPATHER "Therapeutic options for hepatitis B and C: A French cohort" is a multicentre observational cohort which aims to include 15,000 HCV- and 10,000 HBV-infected patients. We selected all participants (n=768) with a HCV genotype 1 who initiated sofosbuvir (400mg/day) and daclatasvir (60mg/day) before October 1st 2014, with or without ribavirin (1-1.2g/day) for a duration of 12weeks or 24weeks. The main endpoint criterion was sustained virological response at 12weeks (SVR12), defined by the absence of detectable HCV-RNA 12weeks after the last treatment intake. Missing SVR12 measurements were imputed using SVR24 measurements (n=45), otherwise considered as virological failure (n=18). Results - A SVR12 was obtained in 729/768 (95%) patients, ranging from 92% (12-week sofosbuvir+daclatasvir) to 99% (24-week sofosbuvir+daclatasvir+ribavirin). The SVR12 rates did not significantly differ between the 24-week (550/574 (96%)) and the 12-week (179/194 (92%); p=0.0688) durations or between regimens with (165/169 (98%)) or without ribavirin (564/599 (94%); p=0.0850). The SVR12 rate was greater than 97% in non-cirrhotic patients irrespective of the treatment duration or the addition of ribavirin. Among cirrhotic patients, the SVR12 rate was higher with 24 than 12-week regimen (423/444 (95%) vs. 105/119 (88%); p=0.0054). Conclusion - The sofosbuvir+daclatasvir combination is associated with a high rate of SVR12 in patients infected by genotype 1, with an optimal duration of 12weeks in non-cirrhotic and 24weeks in cirrhotic patients. The number of patients receiving ribavirin was too low to adequately assess its impact. Lay summary - The sofosbuvir+daclatasvir combination of antiviral drugs is associated with a high rate (95%) of viral eradication in patients infected by HCV genotype 1. The best duration of a ribavirin-free sofosbuvir+daclatasvir combination seems to be 12weeks in non-cirrhotic patients and 24weeks for those with cirrhosis. Clinical trial number: NCT01953458.
Published: 2017

34. A 2-year multicenter, double-blind, randomized, placebo-controlled study of bezafibrate for the treatment of primary biliary cholangitis in patients with inadequate biochemical response to ursodeoxycholic acid therapy (Bezurso)

Author: Eric Nguyen-Khac, Olivier Chazouillères, Dominique Larrey, Isabelle Ollivier-Hourmand, Armando Abergel, Alexandra Rousseau, Tabassome Simon, Anne Minello, François Habersetzer, Christophe Corpechot, Dominique Guyader, Fabien Zoulim, Odile Goria, Olivier Roux, Gisèle N'Kontchou, Jean-Pierre Bronowicki, C. Silvain, Farid Gaouar, Jean-Pierre Zarski, R.E. Poupon, V. de Ledhingen, Patrick Potier, Alexandra Heurgué-Berlot, Maryline Debette-Gratien, P. Mathurin, Jérôme Boursier, Maladies fibro-inflammatoires d’origine métabolique et biliaire du foie [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'hépato-gastro-entérologie [Rennes] = Gastroenterology [Rennes], CHU Pontchaillou [Rennes], Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Régional d'Orléans (CHRO), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, Institut d'astrophysique spatiale (IAS), Université Paris-Sud - Paris 11 (UP11)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National d’Études Spatiales [Paris] (CNES), Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Cellules souches normales et cancéreuses, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire de Reims (CHU Reims), Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 (GRAP), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CIC AP-HP (hegp Ex-Broussais)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital Jean Verdier [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: medicine.medical_specialty, Bezafibrate, animal structures, Hepatology, business.industry, health care facilities, manpower, and services, [SDV]Life Sciences [q-bio], education, Placebo-controlled study, Gastroenterology, Ursodeoxycholic acid, Double blind, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, 030211 gastroenterology & hepatology, In patient, business, health care economics and organizations, medicine.drug
Abstract: International Liver Congress / 52nd Annual Meeting of the European-Association-for-the-Study-of-the-Liver-Disease, Amsterdam, NETHERLANDS, APR 19-23, 2017; International audience
Published: 2017

35. A Single Test Combining Blood Markers and Elastography is More Accurate Than Other Fibrosis Tests in the Main Causes of Chronic Liver Diseases

Author: Dominique Salmon, Paul Calès, Victor de Ledinghen, Brigitte Le Bail, Alexandra Ducancelle, Julien Vergniol, Jean-Pierre Zarski, Vincent Leroy, Eric Nguyen Khac, Nathalie Sturm, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépato-gastroentérologie [CHU Grenoble Alpes], Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Département d'anatomie et cythologie pathologique, CHU Grenoble-Hôpital Michallon, Laboratoire d'anatomie pathologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Département d'hépato-gastroentérologie, CHU Grenoble-Université Grenoble Alpes (UGA), Service d'Hépato-gastroentérologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Service Maladies infectieuses et tropicales [AP-HP Hôpital Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Centre d'investigation de la fibrose hépatique [CHU de Bordeaux] (Hôpital Haut-Lévêque ), Hôpital Haut-Lévêque [CHU de Bordeaux], Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), and Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble
Subjects: Adult, Liver Cirrhosis, Male, Pathology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Disease, Severity of Illness Index, End Stage Liver Disease, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Severity of illness, Medicine, Blood test, Humans, Aspartate Aminotransferases, Prospective Studies, Stage (cooking), Prospective cohort study, Retrospective Studies, medicine.diagnostic_test, business.industry, Platelet Count, Liver Diseases, Fatty liver, Gastroenterology, Middle Aged, medicine.disease, 3. Good health, Liver, ROC Curve, 030220 oncology & carcinogenesis, Elasticity Imaging Techniques, 030211 gastroenterology & hepatology, Female, Elastography, business, Biomarkers
Abstract: International audience; BACKGROUND AND GOAL: International guidelines suggest combining a blood test and liver stiffness measurement (LSM) to stage liver fibrosis in chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD). Therefore, we compared the accuracies of these tests between the main etiologies of chronic liver diseases.STUDY: Overall, 1968 patients were included in 5 etiologies: CHC: 698, chronic hepatitis B: 152, human immunodeficiency virus/CHC: 628, NAFLD: 225, and alcoholic liver disease (ALD): 265. Sixteen tests [13 blood tests, LSM (Fibroscan), 2 combined: FibroMeters] were evaluated. References were Metavir staging and CHC etiology. Accuracy was evaluated mainly with the Obuchowski index (OI) and accessorily with area under the receiver operating characteristics (F≥2, F≥3, cirrhosis).RESULTS: OIs in CHC were: FibroMeters: 0.812, FibroMeters: 0.785 to 0.797, Fibrotest: 0.762, CirrhoMeters: 0.756 to 0.771, LSM: 0.754, Hepascore: 0.752, FibroMeter: 0.750, aspartate aminotransferase platelet ratio index: 0.742, Fib-4: 0.741. In other etiologies, most tests had nonsignificant changes in OIs. In NAFLD, CHC-specific tests were more accurate than NAFLD-specific tests. The combined FibroMeters had significantly higher accuracy than their 2 constitutive tests (FibroMeters and LSM) in at least 1 diagnostic target in all etiologies, except in ALD where LSM had the highest OI, and in 3 diagnostic targets (OIs and 2 area under the receiver operating characteristics) in CHC and NAFLD.CONCLUSIONS: Some tests developed in CHC outperformed other tests in their specific etiologies. Tests combining blood markers and LSM outperformed single tests, validating recent guidelines and extending them to main etiologies. Noninvasive fibrosis evaluation can thus be simplified in the main etiologies by using a unique test: either LSM alone, especially in ALD, or preferably combined to blood markers.
Published: 2017

36. Quantification of portal–bridging fibrosis area more accurately reflects fibrosis stage and liver stiffness than whole fibrosis or perisinusoidal fibrosis areas in chronic hepatitis C

Author: Jean-Pierre Zarski, Jérôme Boursier, Victor de Lédinghen, Brigitte Le Bail, Jeremy Sandrini, Paul Calès, Marie-Christine Rousselet, Julien Chaigneau, Nathalie Sturm, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Département d'anatomie et cythologie pathologique, CHU Grenoble-Hôpital Michallon, Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'anatomie pathologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Département d'hépatologie et de gastroentérologie [CHU Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], BaRITOn - Bordeaux Research in Translational Oncology, and Université de Bordeaux Ségalen [Bordeaux 2]
Subjects: Adult, Liver Cirrhosis, Male, Pathology, medicine.medical_specialty, Cirrhosis, [SDV]Life Sciences [q-bio], Gastroenterology, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, image analysis, Fibrosis, Internal medicine, medicine, Humans, automated segmentation, Stage (cooking), liver biopsy, medicine.diagnostic_test, business.industry, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, 3. Good health, Fatty Liver, Fibroscan, Liver, 030220 oncology & carcinogenesis, Portal fibrosis, Liver biopsy, Disease Progression, Elasticity Imaging Techniques, Female, 030211 gastroenterology & hepatology, Elastography, Steatosis, business, Algorithms, morphometry
Abstract: International audience; Morphometry provides an objective evaluation of fibrosis in liver diseases. We developed an image analysis algorithm using automated thresholding and segmentation to separately quantify the areas and the fractal dimensions of portal–bridging fibrosis and perisinusoidal fibrosis in chronic hepatitis C liver biopsies. We studied 427 digitized liver biopsies and compared the automated measures of the different fibrosis compartments with (1) the Metavir F (fibrosis) and A (activity) histological scores, (2) the digitally assessed area of steatosis, and (3) the liver stiffness measured by elastography (Fibroscan). The perisinusoidal fibrosis area was higher than that of portal fibrosis in stages ≤F2; it reached its highest value in F2 stage and stabilized thereafter. The F3 stage was characterized by equal proportions of portal–bridging and perisinusoidal fibrosis, whereas portal–bridging area was predominant in cirrhosis. Measurement of portal–bridging fibrosis showed highly significantly different values between contiguous F stages; the ratio of portal–bridging fibrosis/perisinusoidal fibrosis displayed less overlap between Metavir stages than did the whole fibrosis area values. Fractal dimension showed that portal–bridging fibrosis tended to display a homogeneous surface-like spatial organization, whereas perisinusoidal fibrosis appeared more heterogeneous according to stage and curvilinear. The portal–bridging fibrosis area was low in cases with low Metavir activity and little steatosis, and became predominant with increasing activity and steatosis. Using stepwise multiple linear regression analysis, the liver stiffness was independently correlated to the portal–bridging fibrosis area (first step, P
Published: 2014

37. Estimated risk reduction of mortality and transplantation with bezafibrate in patients with PBC and inadequate response to UDCA: application of the UK-PBC and Global PBC risk scores to the BEZURSO trial

Author: R. Olivier, Jérôme Boursier, Fabien Zoulim, Odile Goria, M.D. Gratien, Dominique Larrey, Armando Abergel, Tabassome Simon, P. Mathurin, Alexandra Heurgué-Berlot, Eric Nguyen-Khac, Olivier Chazouillères, L.G. Antonia, F.-H. Admane, N. Gisèle, Christophe Corpechot, Jean-Pierre Bronowicki, Alexandra Rousseau, Anne Minello Franza, C. Silvain, François Habersetzer, O.-H. Isabelle, P. Pascal, R.E. Poupon, V. de Ledinghen, Gaouar Farid, and Jean-Pierre Zarski
Subjects: Transplantation, Reduction (complexity), medicine.medical_specialty, Bezafibrate, Hepatology, business.industry, Internal medicine, medicine, In patient, business, Gastroenterology, medicine.drug
Published: 2018

38. Impact de la stéatopathie métabolique sur la survenue d’événements cardiovasculaires et la mortalité des patients BPCO

Author: A. Plazanet, Renaud Tamisier, Maxime Maignan, Marie Joyeux-Faure, I. Jullian-Desayes, Jean-Pierre Zarski, Sébastien Bailly, J.-L. Pépin, Damien Viglino, V. Leroy, and Meriem Benmerad
Subjects: Pulmonary and Respiratory Medicine
Abstract: Introduction La bronchopneumopathie chronique obstructive (BPCO) est reconnue aujourd’hui comme un probleme de sante publique grandissant, a l’origine de couts de sante considerables et d’une surmortalite. La presence de comorbidites en particuliers cardiovasculaires est la premiere cause de mortalite. BPCO et steatose hepatique non alcoolique (NAFLD) sont associees a une augmentation du risque cardiovasculaire. L’objectif est d’etablir la relation entre NAFLD et incidence d’evenements cardiovasculaires/mortalite chez des patients BPCO. Methodes Dans une cohorte prospective de patients BPCO suivis sur une duree de 5 ans, la steatose et la steatohepatite non alcoolique (NASH) ainsi que la fibrose ont ete evaluees par des tests sanguins non-invasifs (FibroMax®). L’impact des hepatopathies sur le critere composite (evenements cardiovasculaires/deces) a ete etudie par des modeles de Cox univaries et multivaries. Resultats Sur 111 patients BPCO suivis, 75 % sont atteints d’hepatopathies (41 % de steatose, 37 % de NASH et 61 % de fibrose hepatique). Apres 5 ans de suivi, on observe la survenue d’evenements cardiovasculaires chez 31 patients et 7 deces. En analyse multivariee, le nombre d’evenements cardiovasculaires et de deces est plus eleve chez les patients fibrotiques que chez les non fibrotiques (HR [95 %CI] : 2,94 [1,18 ; 7,33]). La steatose ou la NASH ne sont pas associees a une augmentation de la survenue d’evenements cardiovasculaires ou de deces. Conclusion Cette etude longitudinale est la premiere a evaluer l’impact des hepatopathies sur le pronostic des patients BPCO. Les patients BPCO atteints de NAFLD montrent un risque accru d’evenements cardiovasculaires. La detection et la prise en charge des hepatopathies pourrait donc ameliorer le pronostic cardiovasculaire chez les patients BPCO.
Published: 2019

39. Chronic Hepatitis B Treatment Initiation and Modification Patterns in Five European Countries: A 2-Year Longitudinal, Non-Interventional Study

Author: Patrick, Marcellin, Victoria, Arama, Hakan, Leblebicioglu, Jean Pierre, Zarski, Stefan, Zeuzem, Stefan, Mauss, Jerzy, Sieklucki, Monica, Acalovschi, Gaye, Usluer, Isabelle, Klauck, Edith, Morais, Stefan, Bjork, Benedicte, Lescrauwaet, Driss, Kamar, Krzysztof, Simon, Tansu, Yamazhan, Hôpital Michallon, Saarland University [Saarbrücken], Medizinisches Versorgungszentrum = Center for HIV and Hepatogastroenterology [Düsseldorf], Department of Medicine III, University Iuliu Hatieganu, the AI463-121 European Longitudinal Chronic Hepatitis B Study Group, and Ondokuz Mayıs Üniversitesi
Subjects: Adult, Male, Hepatitis B virus, Pediatrics, medicine.medical_specialty, Guanine, Adolescent, [SDV]Life Sciences [q-bio], Organophosphonates, Alpha interferon, medicine.disease_cause, Antiviral Agents, Polyethylene Glycols, Hepatitis B, Chronic, Chronic hepatitis, medicine, Humans, Pharmacology (medical), Hepatitis B e Antigens, Longitudinal Studies, Prospective Studies, Disease management (health), Tenofovir, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Pharmacology, business.industry, Adenine, Disease Management, Interferon-alpha, Lamivudine, Alanine Transaminase, Middle Aged, Hepatitis B, medicine.disease, Recombinant Proteins, Europe, Infectious Diseases, DNA, Viral, Non interventional, Female, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: Background Chronic hepatitis B (CHB) is an important health concern, but there are few studies describing its management in different countries. This prospective, longitudinal, non-interventional study aimed to assess differences in CHB management in five European countries (Germany, France, Poland, Romania and Turkey). Methods Data were collected from CHB patients’ records between 2008 and 2010. Patients were stratified by treatment status at baseline (treated or untreated). The primary objective was to estimate the probability of a CHB management modification (treatment initiation or change) among patients from each country during a 2-year follow-up. Results A total of 1,267 patients were included (567 treated, 700 untreated). Baseline characteristics between countries and treatment status groups were broadly comparable. Most patients had an alanine aminotransferase measurement in the 12 months prior to baseline; proportions of patients with an HBV DNA assessment varied by country and treatment status. The Kaplan–Meier-estimated probability of any treatment modification ranged from 9.4% (Turkey) to 30.1% (Poland) at 12 months and 10.0% (Turkey) to 40.0% (Poland) at 24 months. Modifications were more common in treated than untreated patients. The most frequently reported reasons for modifying treatment were HBV-DNA-related. The majority of treated patients were treated with monotherapy; however, choice of therapy differed between countries. Conclusions This is the first longitudinal study describing CHB management in European countries. Differences were observed in treatment and monitoring between countries, but alanine aminotransferase and HBV DNA levels consistently emerged as key tests in the management of CHB in all five countries.
Published: 2013

40. Performance of an antigen–antibody combined assay for hepatitis C virus testing without venipuncture

Author: Marie-Noelle Hilleret, Cécile Bourdon, Cécile Garnaud, Myriam Blanc, Jean-Louis Quesada, Vincent Leroy, Raphaele Germi, P Leclercq, Jean-Pierre Zarski, Monique Baccard, Sophie Mathieu, Sylvie Larrat, Patrice Morand, and Anne Signori-Schmuck
Subjects: Adult, Male, Fingerstick, Point-of-Care Systems, Hepatitis C virus, medicine.disease_cause, Sensitivity and Specificity, Young Adult, Phlebotomy, Antigen, Virology, medicine, Humans, Saliva, Dried blood, Antigens, Viral, Aged, Immunoassay, Venipuncture, biology, Clinical Laboratory Techniques, business.industry, virus diseases, Hepatitis C Antibodies, Middle Aged, Serum samples, Hepatitis C, digestive system diseases, Blood, Infectious Diseases, biology.protein, Female, Antibody, business
Abstract: Background Hepatitis C virus (HCV) is underdiagnosed and therefore increasing the opportunities for HCV testing without venipuncture may be useful. Objectives We evaluated the analytical performance of a modified, commercially available, combined HCV antigen–antibody assay (cEIA) (Monolisa ® HCV-Ag-Ab-ULTRA) and a commercially available point-of-care (POC) device (OraQuick ® HCV) on fingerstick blood (FSB) and oral mucosal transudate (OMT). Study design FSB, OMT and serum samples were collected from 113 cases of HCV-antibody-positive patients and 88 HCV-antibody-negative controls. The HCV-antibody-positive group included 63 patients with quantifiable HCV-RNA (56%) and 17 HIV/HCV co-infected patients (15%). FSB and OMT specimens were collected as dried blood spots (DBSs) or with the OraSure collection system, before testing with cEIA. Results With FSB specimens, the cEIA and the POC device exhibited 100% specificity and 98.2% and 97.4% sensitivity, respectively. The specificity of the cEIA in FSB sharply decreased if stored 3 days at room temperature. With OMT specimens, the cEIA sensitivity (71.7%) and specificity (94.3%) were significantly lower than the performance of OraQuick ® HCV (sensitivity, 94.6%; specificity, 100%). The optical densities obtained with the cEIA in FSB and OMT were lower in HIV/HCV co-infected patients compared with HCV monoinfected patients. Conclusion The cEIA using FSB specimens collected on DBSs preserved in appropriate storage conditions was a reliable alternative, equivalent to the POC assay, for HCV testing without venipuncture. The cEIA was not adapted for HCV testing on OMT.
Published: 2012

41. Clinical features and prognostic factors of listeriosis: the MONALISA national prospective cohort study

Author: Odile Fremin-Batteux, Juliette Clarissou-Philippe, Benoît Jauhlac, Severine Guyetand, Jacques Gasnault, Corinne Haioun, Liamine Aissaoui, Marie-Christine Pages, Marie-Pierre Fos, Christian Rose, Didier Hubert, Marie-Rose Rothe, N. Bouziges, Benoît Huc, François Devianne, Sabine Bidart, Anne Forest, Kevin Bertrand, Mohamed Eldeghedy, Annick Verhaeghe, Caroline Malderet, Anne Bertrou, Bernard Guerquin, Catherine Duche, Muriel Archambaud, Rabea Cotteret, Olivier Toullalan, Yves Devaux, Smail Bergheul, Valérie Sivadon-Tardy, Pierre-Gilles Merville, Geneviève Blanchard-Marche, Didier Raoult, Bernard Hory, Florence Richardin, Evelyne Belle, Mohamed Menouar, K Guitteaud, Mohamad Mohty, Ambroise Montcriol, Max Laurin, Aurélia Picard, Jean-Paul Mira, Marie-Charlotte Chopin, Richard Bonnet, Michel Wolff, Sébastien Maillez, Jeanne Maugein, Véronique Leblond, Nicola Walid, Bernard Gauche, Mathieu Evillard, Hassen Jeddi, Anne Bourlet, Isabelle Grawey, Thierry Jault, Sandrine Hiret, Valerie Gaborieau, Véronique Boin-Gay, An Kim, Thierry Constans, Jean-François Gaide, Martine Giraud, Eric Meaudre Desgouttes, Alain Fur, Abdallah Maakaroun, Olivier Matray, Bertrand Maubert, Frédérique Péchinot, Aurelie Garbi, Claire Delbrouck, Benoît Grandclerc, Vincent Cadiergue, Hervé Lécuyer, Bernadette Grignon, Thierry Bensaid, Nicole Constantin, Yannick Chevalier, Hassène Rahmani, Thierry Levent, Joelle Desliers, Florence Van de Velde, Xavier Adhoute, Clara Andriau, Christophe Charasse, Rémi Vatan, Benoît Martha, Alain Lecis, Didier Albert, Romain Jacobs, Hélène Lefranc, Christian Martin, Nasseur Rezgui, Bertrand Pigeon, Catherine Le Henaff, Dominique Cassignard, Françoise Cotes, Eric Pujade Lauraine, Jean-François Gattault, Nicole Ferreira-Maident, Noémie Jourde-Chiche, Hélène Garrec, Olivier Darchen, Carole Schwebel, Marie-Christine Bezian, Patrick Daoud, Tsouria Becaid, Simone Laluque, David Broche, Christine Boisselier, Pascale Martres, Sarah Hammami, Brigitte Olivier, Jean-Marie Nkunzimana, Eric Monlun, Isabelle Marterl-Lafay, Marion Carboni, Marie-Françoise Mattei, Sandrine Castelin, Isabelle Barillot, Marie-Noelle Cufi, Thomas Kaiser, Catherine Herry, Pascal Hutin, Jean-Pierre Bronowicki, Bernard Branger, Pierre Thomas, Elie Zagdoun, Anne Goquelin, Ziad Assaf, Ingrid Croquet, Bruno Pozzetto, Thomas Similowski, Anne-Isabelle Briere, Marie-Thérèse Albertini, Mariam Blaka, Christelle Tassot, Anne Gaschet, Jean-Philippe Lavigne, Antoine Pujol, Philippe Colombat, Edouard Devaud, Hana Talabani-Boizot, François Barière, Anne-Marie Cordier, Philippe Gueudet, Georges Simon, Anne-Sophie Lipovac, Françoise Bandaly, Anne Beauplet-Lepage, Sylvie Prince, Charlotte Jouzel, Jean-Luc Deboutin, Patrick Zavadil, Louis Puybasset, Marie-Cécile Petit, Loïc Guillevin, Kamel Touati, Christophe Ntalu Nkato, Sylvie Carette, Jacques Vaucel, Chantal Delasalle, Marine Gross Goupil, Laurent Gutmann, Christiane Payen, Annick Barboteau, Firouzé Bani-Sadr, Christophe Legendre, Philippe Roulier, Elie Azria, Ibrahim Farah, Isabelle Rouquette-Vincent, Anne-Sophie Erena-Penet, Philippe Labadie, Eric Josien, Aicha Derragui, Mathieu Legrand, Odile Beyne-Rauzy, Jean-Marc Nabholtz, Marie-Joelle Demarcq, Olivier Garosi, Michel Deiber, Fabrice Chaix, Bertrand Souweine, Anne Collignon, Gisèle Renard, Mickael Jego, Gilles Bernardin, Anne Allart, Jocelyn Barrier, Marc Vasse, Philippe Ménager, Marc Wurmser, Abderkader Ouazir, Olivier Gontieron, Yvon Berland, Sébastien Trouiller, David Leysenne, Christophe Ozanon, Fanny Autret, Tahar Saghi, Loïc Dopeux, Sophie Benoit-Coustou, T. Fraisse, Christine Maillard, Karine Nikodijevic, Georges Kaltenbach, Angéline Jamet, Philippe Aucher, Julie Bottero, Marie-Claude Piffaut, Marianne Besnard, Florence Courillon, Marie Bonfils, Christine Ghevaert, Marie Destors, Eliette Jeanmaire, Franck Zerbib, Manuel-Luis Gameiro, T Prazuck, Laurent Mandin, Olivier Guisset, Marguerite Fines, Toufik Feddal, Agnès Jouffret, Louis Mesnard, Thomas Bourrée, Hasinrina Razafimahefa, Sylvestre Tigaud, Vincent Estève, Philippe Malherbe, Jean-Michel Salord, Pascal Adam, Bertrand Rozec, Michel Fuillet, Olivier Lemenand, Denis Quinsat, Ana Danalaché, Véronique Vialette, François Brosset, Patrick Messner Pellenc, Nicolas Heisel, Edouard Girard, Régine Martin, Olivier Garesslin, Catherine Mille, Alexandre Gascon, Marc Nicolino, Laurence Mouly, Claire Fabre, Bénédicte Ponceau, Marie-Etiennette Emeriau, Pascal Cathebras, Bérangère Bernardaud, Michèle Pérouse de Montclos, O. Arsene, Karine Grenet, Yazdan Yazdanpanah, Sten De Witte, Anne Scemla, Laurence Bouillet, Christophe Burucoa, Vincent Loffeier, Séverine Visentin, Luc Desfrere, Miloud Arabi, Frédérique Costa, Sylvie Lechat, Ali Chekroun, Raymond Ruimy, Marie, Jérôme Bizet, Xavier Nassif, Baihas Dib, Patrick Bert-Marcaz, Laurent Martin Lefèvre, Nicholas Sedillot, Blandine Cattier, Emilie Boidin, Daniel Sondag, Aude Bourrouillou, Alain Noirot, Franck Desemerie, Fréderic Heluwaert, Catherine Tamalet, Marc G. Berger, Jean-Daniel Lelièvre, Dominique Perotin, Abdelkader Bemrah, Alain Lozniewski, Bernard Borstein, Hanna Eid, Diana Suatean, Virginie Mignaut, Jean-Claude N'guyen, Valérie Le Goff, Laurent Teillet, Christophe Rolland, Gwenaël Alfonsi, Florence Lachenal, Philippe Bossi, Yves Botreau, Florence Doucet Populaire, Henry Jardel, Nicolas Gallo, Elias Jabre-Sikias, Michel Dupon, Hélène Brihier, Isabelle Patry, Alexandre Leclercq, Bernadette Tourrand, Christophe Roussel, Jean-Emmanuel Kurtz, Bénédicte Paindaveine, Simon Elhadad, Richard Sanchez, Eric Sgro, Pierre Berger, Valérie Murbach, Anne Holstein, Florence Martin, Taoufik Merabet, Amélie Benbara, Milagros Ferreyra, Laure Esposito, Pierre Delobel, Antoine Andremont, Marc Bourlière, Carole-Anne Boudy, Jean-Baptiste Gaulthier, Laurent Tacchini, Olivier Marpeau, Sonia Tesseydre, Marie-Pierre Coulhon, Nathalie Hodee, Marie-Chrsitine Conroy, Pierre Weinbreck, Roland Leclercq, Laurent Souply, Christian Bidault, Annie Elbez, Marie-Annick Lebreton, Patrick Brisou, Agnès Ferroni, Jean-Louis Pourriat, Nadia Anguel, Christian Noel, Philippe Jouvencel, Eric Pichard, Xavier Martin, Mathieu Coste, Pierre Zuber, Catherine Neuwirth, Jean-Pierre Hacot, Paul Aye, Jérôme Guinard, Yves Pean, Jean-Christophe Dengo, Fabrice Petassou, Didier Viole, Thierry Messiaen, Jean Beytout, Philippe Petitjean, Ferdinand Savare, Patrice Cuvillier, Sophie Coignard, Hélène Anglaret, Nassim Kamar, Elisabeth Chachaty, Karine Guimard, Louis Braem, Hacene Fezoui, Pierre Martin, Jean-Paul Viard, Claire Larroche, Nicolai Claudiu-Plesa, Thierry Benoit-Cattin, Olivier Moquet, Thierry Pasdeloup, David Rosay, Rodolphe Jean, Jean-Bernard Mariette, Marc Debouverie, Hervé Peltier, Mustapha Terki, Jacques Daleas, Valérie Dattin-Dorrière, Michel Vergnaud, Emmanuel Grimprel, Sylvène Rosselli, Jean-Marc Didier, Pierre Faurie, Luc Frimat, Aziza Mandjee, Sabine Etchemendy, Pierre Tissières, Jean Nakhleh, Sylvie Mariette, Christian Perronne, Bruno Carbonne, Nathalie Houssiaux-Maisonneuve, Tristan Ferry, S Beague, Anthony Sebban, Marie-Thérèse Hili, Jean-Michel De Kermadec, Lucien Brasme, Gilles Blaison, Caroline Garandeau, Jean-Pierre Sollet, Laurent Tronchon, Thierry Samson, Julien Gesquière, Nicolas Ettahar, Alain Créange, Etienne Laurens, Véronique Equy, Fréderic Bart, Bernard Bouffandeau, Christine Vaillant, Valerie Pesque, Jean-Marc Lalot, Marc Levy, Michel Kaidomar, Mihaela Saplacan, Sterenn Yvenou, Marie-Isabelle Steibach, Emmanuelle Cambau, Agnès Riche, François Fourrier, François Raffi, Mélissa Lalu, Henri Bérard, Danielle Clave, Jean-Claude Mouries, Martine Porcheron, Jean Cabalion, Richard Lamarca, Nathalie Canu, Jean-Baptiste Roseau, Annabelle Stoclin, Luca Luminitan Elena Lupean, Rémi Gebeile, Celia Salanoubat, Carole Marmouset, Pierre Bigot, Anne-Laure Breton, Pierre Kalfon, Colette Vincent, Sophie Marty, Olivier Tandonnet, Alexis Redor, Xavier Valette, Ourida Aoudia, Jacques-Arnaud Seyrig, Bertrand Beaune, Hugues Aumaitre, Georges Pinon, Yann Leveneur, Sylvie Charachon, Raoul Herbrecht, Henriette de Valk, Gary David, Julien Pouyanne, Marc Dommergues, Majed Al Chaar, Véronique Blanc-Amrane, Pascale Guillarmé Grossmann, Bruno Abraham, Yves Morel, Philippe Suel, Denis Sautereau, Olivier Guilloy, Tu Anh Tran, Frédéric Laurent, Zahir Amoura, Jacques-Olivier Bay, Zoubida Elharie-Heraux, Joyce Sibony-Prat, Bernard Guillois, Dominique Rohmer-Heitz, Audrey Barrelet, Jérémie Courouble, Jean-Paul Herry, Daniel Vittecoq, Annie Vermesch-Langlin, Jean Auroux, Claude Aubert, Thierry Harvey, Ghislaine Lamoine-Gimet, J. Riahi, Florence Soraudeau, Bachar Al-Jalaby, Caroline Périsson, Khélifa Ayouz, Florence Cardot, François Maillet, Alain Goux, Théophile Magna, Bertille de Barbeyrac, Adrien May, Dominique Andreotti, Olivier Jonquet, Hélène Dumouchel, Didier Thibaud, Philippe Morlat, Pascal Chevalet, Pascal Ancelin, Guy Chambreuil, Cécile Le Boterff, Anne Ceriez, Olivier Detante, B Pangon, Claude C.A. Bernard, Vincent Cailleaux Pierre-Etienne Cailleux, Jordi Miatello, Pierre-Yves le Berruyer, Sylvain Kouaho, Michel Briaud, Hélène Delaby, Patrick Herbecq, Christine Segonds, Véronique Jault, Pascale Brunel, Christine Dussopt, Jean Thore, Jean-Marc Thouret, Jean-Marc Kerleau, François Le Baron, Slavius Matica, Sophie Leautez-Nainville, Matthieu Pecquet, Laurent Bret, Yacine Sedjelmaci, Pierre Metton, Habiboulaye Diallo, Jany Rey Zermati, Arnaud Delahaye, Hélène Chaussade, Laurent Mandelbrot, Emilie Bessede, Olivier Casanovas, Paul Pierrot, Annick Legras, Dominique Lauque, Hélène Gatti, Jean Catineau, Ebutu Likose, Gilles Capellier, Eric Kibbrecht, Freddy Thibaut, Patrick Valadier, Chantal Lemble, Joël Gaudelus, Joelle Mellier, Joëlle Brochen, Emmanuel Gascou, Stéphane Bonacorsi, Stéphanie Bannier, Bruno Fantin, Didier Raffenot, Valérie Revel, Hakim Amroun, Huguette Negrery, Anne-Laure Fauchais, Paul Mercury, Michel Chuzeville, Christian Zumbo, Nicolas Després, Pascal Roblot, Jérôme Pasche, Jean Claude Boufetteau, Jocelyne Caillon, Julien Boileau, V. Rabier, Benjamin Manéglier, Emilie Jourdes, Franck Ceppa, Christine Recule, Nicolas Degand, Benoît Henry, Thierry Baranger, Dominique Pateron, Agnès Pélaquier, Gérard Bouchet, Hélène Fiette, Ozel Guiden, Dana Ranta, Etienne Ruppé, Nabil Chiouk, Jacques Breuil, Dominique Leduc, Véronique Loustaud, Hervé Métenier, Michel Durand, Isabelle Mahé, Leila Karaoui, Marie-José Collus, Mehran Monchi, Olivier Belmonte, Romain Blondet, Jacques Thierry, Karine Humbert, Gilles Salama, Marie-Noelle Heurtaux, Cécile Goujard, Bruno Sivery, Martial Boisseau, Redouane Dahoumane, Pierre Delour, Christian Niels Meyer, Anne Faudon-Gibelin, Gérard Poulain, Roger-Charles Luciani, J.-C. Souquet, Olivier Grossi, François Vandenesch, Sylvain Mermont, Jacques Bronner, Sonia Dahan, Paul Marzouk, Pascal Pouedras, Noureddine Djafari, François-Xavier Caroli-Bosc, Jean-François Dessin, Brigitte Gruffat, Armelle Morin-Fatome, Sylvie Thoinet, Bano Konate, Jean-Winoc Decousser, Claire Poyart, Patrick Plessis, Olivier Millet, Vincent Cattoir, Françoise Geffroy, Manica Vasseur, Pierre Carli, Isabelle Citony, Christian Richard, Nicolas Sigur, Patrick Marthelet, Luwawu Mbimba, Pierre Feugier, Philippe Sauder, Hama Djerad, Evelyne Bourgerette, Hanen Chahtour, Adrien Lemaignen, Dominique Bechade, Patrick Ochocki, Antoine Vieillard Baron, Dominique Astruc, Marie-Pierre Moiton, Nicolas Dubois, Sylvie Ledru, Corinne Seknazi, Hélène Poupet, Jean-Philippe Brieux, Gérard Barthélémy, Aihem Yehia, Louis-Jean Couderc, Ahmed, Françoise Rigaux, Yohann N'guyen, Philippe Bethery, Damien Corberand, Etienne Auvray, Paul-Louis Woerther, Christian Combe, Sophie Delesalle, Jean-Marie Piala, Faraj Al Freijat, Philippe Juvin, Malcolm Lemyze, Hyacine Rey, Claire Larible, Noel Milpied, Lémia Zgarni, Julia Gaillard, Agnès Juven, Paola Otean, Adrien Melis, André Pechinot, Olivier Bouchaud, Olivier Chassin, Pierre Hausfater, Asma Trabelsi-Jnifen, Vincent Grobost, Didier Lemery, Pierre Soury, Françoise Brevet, Jacques Tankovic, Dominique Sansot, Jean Louis Salomon, Charlotte Cordonnier, Brigitte Lamy, Antoine Maisonneuve, Dominique Pressac, Claude Rémy, Rodolphe Sobesky, Stéphanie Cognet, Pierre Cougoul, Didier Jan, Dominique Perrotin, Cécile Hombrouk-Alet, Thierry André, Gilbert Pochmalicki, Serge Girard, Vincent Zerr, Guillaume Cadiot, Claudine Lasbasses, Michel Slama, Abderrazak El Yamani, Sophie Brovedani, Jean Armengaud, Romain Hernu, Géraldine Mascade, Aurélien Lorléa'ch, Ali Akkari, Mathieu Tourdjman, Christopher Payan, Eric Jullian, Nathalie Fonsale, Frédéric Riehl, Paul Strock, Geneviève Grise, Philippe Mottaz, Christian Floriot, Marie-Noëlle Ungeheuer, Denis Caillot, Arnaud Chalvon-Demersay, Catherine Branger, Stanislas Bruley des Varannes, Marc Paccalin, Marie-Pierre Danjean, Alexandre Mebazaa, Xavier Brunet, Roland De Varax, Laurence Delhoustal, Sophie Haro, Bruno Chabanon-Pouget, Isabelle Goidin, Dominique Chudersky, Corinne Costes, Delphine Chatellier, Maud Gelez, Damien Dassant, Pascal Joly, Jean-Michel Arnal, Zakaria Hamitou, Philippe Rondepierre, Carole Pignon, Valérie Crombe, Amanda Lopes, Chrystelle Kemenar, Olivia Raulin, Anne-Cécile Hochart, Sandrine Gérart Pons, Valérie Zeller, Guillermo Reyes Ortega, Mathilde Guérin, Audrey Migraine Bouvagnet, Florence Eboue, Isabelle Loury-Lariviere, Sophie Leotard, Suzanne Lima, Marie Kassis, Jean-Luc Donay, Jean-Pierre Audié, Guillaume Cartron, Arnaud Ribier, Fanny Buron, Mirela Tuca, Marius Semenescu, Arnaud Serre, Vincent Quentin, Denise Bouyssou-Destriau, Violaine Bresson, Christine Chandesris Joséphine Chapalain-Cagnon, Eric Cua, Henri Courtade, François Bénézit, Sébastien Lamache, Philippe Bonnefoy, Francis Schneider, Richard Monarchi, Adeline Schendel, Paramasiven Mootien, Ghislaine Gardes, Pierre-François Westeel, Jean-François Magny, François Caron, Jocelyn Michon, Didier Eyer, Isabelle Ronda, Pierre-Yves Robillard, Frédéric Renou, Anna Faucher, Jean-Robert Harlé, Anne Debernardi, Grégory Akerman, Benoît Fontenel, Pierre Hourdebaigt-Larrusse, Marie-Noëlle Adam, Aude Lessene, Abdelkader Hrichi, François Blot, Athéna Le Pierres, Romain Lemarie, Françoise Granier, Véronique Tardy, Marc Gatfosse, Pierre-Marie Roger, François Goupil, Saïd Aberrane, Franck Bernardi, Isabelle Plantier, Nathalie Funakoshi, Jean-Gilles Delecalle, Patricia Barbut, Jacques Reynes, Christophe Roy, Sophie Perreve, Michel Garre, David Ribes, Cyrille Ede, Jean-Claude Dausset, Francis Duchene, Jean Caussin, Michelle Becker-Schneider, Gilles Berthelot, Damien Dupont, Jean-Michel Gillot, Aurélie Messager, Jean-Marie Pannecouck, Jean-Christian Roussel, Alain Reynaud, Sylvie Cariou, Anne Dao, François Guillemot, Martin Martinot, Patrick Casali, Anne-Sophie Poirier, Aissa Kerchache, Necera Sakek, Eric Porthault, Christophe Decoene, Chantal Ache-Papillon, Brigitte Bicais, Jean-Claude Feugier, Thierry Masseron, Charles Marty-Ane, Daniele Goldgran Toledano, Jean-Christophe Dubus, Damien du Cheyron, Dominique Decré, Jean-Loup Pennaforte, Ahmed Tigaizin, Bernard Vache, Eric Oswald, Claire Moulinoux, Anne-Christine Jaouen, Caroline Charlier, Anne-Laure Virlouvet, Ali Kara, Jean-Luc Sicsic, Sylvie Goffart, Mathieu Zuber, Claudine Fèbre, Olivier Lortholary, Mathieu Dupont, Annie Vessieres, Thierry Helvadjian, Thomas Signouret, Cedric Daupin, Sandrine Essouri, Jean-Louis Jacob, Pascal Boileau, Caroline Blazejewski, Quentin Lepiller, Juan-Pablo Maureira, Eddy Lebas, Christophe Deschamps, Amévi Ananivi, Clovis Foguem, Daniel Adoue, Abdourahim Chamouine, Alain Michault, Bruno Guérin, Olivier Baud, Clara Vinci, Thierry Weitten, Jean-Marc Eychene, Marie Froidure, Julien Obiols, Patricia Roussellier, Marc Lecuit, André Cabié, Saskia Foucart, Karim Belhadj, Michel Cingotti, Bruno Dumoulard, Jean Puyhardy, Etienne Danquechin Dorval, Lucile Mendes-Martin, Enrique Casalino, Luc Jarrige, Fabien Lambiotte, Philippe Masson, Mohammed Mansouria, Pierre Thouvenot, Katy Jeannot, Martine Nyunga, Valérie Macci, Florent Masia, Claire Briere de la Hosseraye, Wassila Anteur, André Sommabère, Marie-Claude Germain, Isabelle Arnault, Bernard Carbonelle, Philippe Devos, Daniel Protar, Tiphaine Gaillart, Ludovic Lassel, Laurence Hamou-Plotkine, David Trystram, Thierry Bureau, Olivier Collard, Fanny Vuotto, Sophie Malhiere, Frederique Canis, Gillles Plainfosse, Catherine Lechiche, Bertrand Lassere, Martine Chouraqui, Jean Baptiste Michot, Fethi Radhouane-Khanjari, Carole Barbier, Pascal Bonitchi, Abdelaziz Benkhelil, Odile Salmon, Laurent Damaj Gandhi, Bertrand Minguet, Michel Wagner, Odile Falguières, Zahr-Eddine Ali Chaouche, Eric Zaoui, Isabelle Guichard, Bernard Huttin, Apollinaire Karirisi, Gaël Cinquetti, Christophe Plane, Lionel Rostaing, Yanne Henry-Andrieu, Daniel Re, Virginie Verrier, Pascal Bolot, Michel De Biasi, Laurence Vrigneaud, Mathilde Turpin, Marie-Claude Demachy, Etienne Roussel, Michèle Blancs, Olivier Join-Lambert, Yves Ville, Thierry Granger, Gilles Hilbert, Virginie Medeau, Daniel Villers, Benoit Pilmis, François Gouraud, Emmanuel Ardiet, Catherine Heyraud-Blanchet, Alain Devidas, Hélène Dieye, Julie Cremniter, Jean-François Bergmann, Rozenn Le Berre, Virginie Leguen, Daniel Royer, Gilles Le Maout, Christian Harou, Sylvie Gabriel-Soléan, Yves Regouby, Martine Pestel-Caron, Patrick Brunet, David Boutoille, Emmanuelle Bonnin, Patrice Coulon, Marc Sullice, Marianne Barbieux, Gilles Cambonie, Joëlle Tricoire, Marie-Nadège Bachelier, Delphine Briend, Céline Ramanantsoa, Nathalie Bednarek, Didier Lebreton, Julien Lagrandeur, Damien M'Bey, Philippe Audeguy, Elie Saliba, Lena Damaj, Hassan Fallouh, Pascal Couturier, Fabrice Prévost, Yves Domart, Marie-Odile Lafforgue, Anne Le Du, C. Beuscart, Pierre Guillet, Fabrice Larrazet, Marie-Hélène Hausermann, Henri Robert, Nicolas Fanjaud, François Goehringer, Thomas Bachelot Philippe Badia, Jean-Michel Coulaud, Cristel Fissore Magdelein, Renaud Defebvre, Anne-Sohie Moreau, Johan Courjon, Gilles Salles, Michel Mialon, Silvia Iacobelli, Emmanuelle Bille, Marie-Christine Barbier, Yves Aubard, Patrice Badila, Jean-Philippe Rasigade, Alban Deroux, Evelyne Lecaillon-Thibon, Michel Godin, Abdelmajid Djeffal, Viorica Badurescu, Meriem Canitrot, Pierre Blanchard, Antoine Legros, Laurence Got, Françoise Duluc, Mylène M. Maury, Gilles Dassieu, Nordine Khodeir, Jean-Marie Duez, Mathieu Morincomme, Jérôme Lacroix, Mathieu Revest, Koffi Blewoussi, Isabelle Barazer, Françoise Poitevin, Camille Seignovert, Stéphanie Honore Bouakline, Anne Heidt, Brigitte Malbruny, Julien Desblache, Christian Cattoen, Eric Jaunait, Bruno Chaminade, Claude Bazin, Jonathan Chelly, Anne Pottier, Alain Schmitt, Alain Tissot, Karim Dadoun, P. Rebattu, Claudine Contamin, Arnaud Guerard, Nathalie Ravet, Sandrine Khalifa-Thellier, Marlène Chatron, Gaëlle Dörr, Hélène Biessy, Emmanuel Forestier, Bruno Devaux, Jean-Jacques Grelaud, Xavier Tchenio, Marie-Cécile Ploy, Jérémie Violette, Michèle Burdin, Lionel Falchero, Dominique Jacomy, Jean-Christophe Rozé, Damien Labarriere, Stéphane Leroux, Corinne Meregnani, Assia Ferhat Carre, Paul Orode, Jean-Gabriel Paul, Catherine Godon, Agnès Vinay, Régine Barraduc, Dominique Dallay, Alexandre Ampère, Anne-Gaelle Kervegant, Guillaume Louart, Dominique Beal Ardisson, Francoise Leonetti, Jean-Yves Baril, Stéphanie Haiat, Bincy Darre, Jérôme Bay, Yvan Gauthier, Sylvie Radenne, Pierre-Yves Gueugniaud, Philippe Ravaud, Luc Landraud, Guillaume Ranchon, Loïc Chimot, Véronique Duval, Ilhem Agha-Mir, Sabine Camiade, Estelle Wafo, Jean-Patrick Laporte, Mariam Roncato-Saberane, Camille Bron, Patrice Laudat, Samir Kennouche, Nawel Afroukh, Dominique Neri, Hakim Kherouf, Yoar Hichri, Pierre-Edouard Bollaert, Gwenaelle Vary, Denis Castaing, Christine Lefort, Sébastien Rouget, René Robert, Christelle Guillet-Caruba, Catherine Simonin, Alain Vighetto, Severine Cabasson, Alain Brusset, Alexandra Doloy, Christel Cherlet, Ahmed Rouidi, Marina Salvucci, Réginald Pordes, René-Gilles Patrigeon, Emmanuelle Dupre-Narlet, Jacques Minet, Fethi Taleb, Anne-Marie Colingorski, Tahar Hadou, Sylvain Diamantis, Isabelle Glorieux, Thierry May, Jean-Claude Colombani, Anne Berth-Farges, Nicole Desplaces, Renaud de Tayrac, Elisabeth Walter, Fabienne Lorge, Pascal Reboul, Nathalie Dournon, Laurence Estépa, Marie-Lina Toubia, Mathilde Flahault, Thierry Delacour, Dominique Hurel, Hélinoro Andriamaneo, Cécile Bébéar, Denis Grasset, Miloud Serier, Oléna Orléva, Nadine Dubroca, Hervé Gentilhomme, Jean-Luc Baudel, Isabelle Lavenu, Salim Smati, Carlo Saroufim, Eric Placidi, Albert Sotto, Benoît Libeau, Hélène Leroy, François Golfier, Christophe Dollon, Laurence Desnoulez, Eric Barre, Daniel Cohen, Pascal Priollet, Thierry Marsepoil, Benoît Lionnet, Jacques Tebib, Pascale Penn, Antoine Bouissou, Christian Roth, Olivier Martinet, Anna Schmitt, Nathalie Fruleux, Fouzia Radaoui, Jean-Marc Lessinger, Virginie Morando, Jean-Jacques Maillet, Christophe Fruchart, François Boué, François Goffinet, Franck Lellouche, Martin Demarchi, Alain Geissler, Jean-Charles Picaud, David Assouline, Patricia Brazille, Philippe Guimier, Marie-Françoise Dabysing, Bruno Delpeuch, Vanessa Tran, Guy Gengembre, Delphine Deligne, Dominique Vodovar, Yvan Touze, Sabrina Parent, Anne Decoster, Camille Dewitte, Emmanuel Weiss, Thierry Lambert, Thomas Guimard, Vincent Caille, Claude Guérin, Françoise Evreux, Geneviève Barjon, Basile Ondze, Damien Fournier, Olivia Bandin, Sophie Mignart, Henri Demontclos, Didier Perez, Jacques Croize, Nicole Desbois-Nogard, Guenièvre Imbert, Clarisse Dupin, Khalid Ridah, Marie-Christine Varin, Guillaume Arlet, Edith De Clareuil, Marie-Line Eustache, Patricia Le Pimpec, Louise Fortin, Eugène Ngami, Fabrice Mihout, Cecilia Esnault, Vincent Bouden, Véronique Annaix, Yves Poinsignon, Aurélien Lorchleac'h, Jean-Marc Degreff, Marie Garofano, Renaud Mesnage, Anne-Marie Roque-Afonso, Alain Chevailler, Stéphane Hominal, Thierry Charbonnier, Adrianna Bildea, Fabien Fily, Benjamin Davido, Emmanuel Rassiat, Assi Assi, Stéphanie Brunet, Hervé Jacquier, Catherine Claise, Annie Durand, Yannick Monceau, Pierre Blanc, Jean-Marie Sire, Yves Sucin, Jean-Pierre Zarski, Nathalie Bronet, Ingrid Lafon, Philippe Rey, Jacques Markarian, Eric Sennevile, Olivier Wink, Guilène Barnaud, Anne-Sophie Peultier, Sabine Taylor, Rim Savatier, Patrick Valayer, Claude Negrier, Selim Jennane, Edouard Begon, Laura Hyerle, Delphine Bridoux, Claire Daurel, Benoît Dalle, Mathilde Lescat, Philippe Stolidi, Elodie Perrodeau, Xavier Heches, Pierre Castelnau, Philippe Bray, Jean-Claude Texier, Serge Rossignol, Maud Brung-Lefebvre, Jean-François Subra, Jean-Marie Delarbre, Morgane Schneerson, Guyro Jang, Mona Mehri, Nathalie Landgraf, Pierre-Marie Girard, Armand Goll, Zaineb Bekguesmia, Christophe Clement, Michel Collet, Vincent Maze, Amine Benjelloul, Solène Durliat-Ellie, Vincent Letouzey, François Schmitt, Valérie Martinez, Sarah Watson, Abderrezak Bouasria, François Barbier, Raphael Lauretta, Mirana Razafimahery, Cristina Sirbu, Patrick Malherbe, Anne Wuillai, Ludovic Lesecq, Philippe Gaudard, Serge Houssaye, Jacques Monsegu, Gilles Rival, Chantal Chaplain, Jean-Didier Grangé, Oana Zamfiri, Florence Nguyen-Khac, Marc Portneuf, Jean-Michel Pawlotsky, Delphine Bonnet, Laurent Traissac, Sophie Hamon-Charles, Didier Dreyfuss, Louis Bernard, Laurence Detourmignies, Olivier Martineau, François Pettinelli, Marc Zandecki, Michel Dreyfus, Alain Chapelle, Sébastien Sabbat, Anne-Sophie Labussiere, Jean-Louis Gaillard, Chloé Plouzeau-Jayle, Patrick Zoveda, Véronique Leflon, Marie Levy, Aurélie Labé, Bruno Soulie, Raoul Jacques Bensaude, Hecham Moussa, Sylviane Catteu, Nathalie Biron, Loïc Masson, Georges Mourad, Nejla Aissa, Dragos Ciocan, Hubert De Boysson, Jean-Luc Bouyer, Patrick Yeni, Thierry-Pascal Zame, Caroline Thomas, François Cavalié, Laurence Koulmann, Christophe Rioux, Olivier Barraud, François Bricaire, Marguerite Le Poulain, Marie-Noelle Noulard, René Thomas, Guy Semet, Laurent Mosser, Olivier Marret, Brigitte Rivière, Vincent Jarlier, Jean-Philippe Coindre, Marc Villemain, Martin Pierre, Yacine Benkaci, Philippe Chiron, Hoang Vu-Thien, Jérôme Gournay, Andrea Labaune-Kiss, Brigitte Lauzanne, Fanny Lemercier, Souad Silhadi, Imad Kansau, Christophe Poncelet, Olivier Baldesi, Francis Thuet, Olivier Leroy, Aurore Lamberet, Camille Petit Hoang, Sophie Micheli, Ayman Abokasem, Hakima Nesrine, Pierre Lureau, Christian Chidiac, Vincent Piriou, Fabien Zoulim, Dieudonné Nicobaharaye, Anne Tixier, Isabelle Matheron, Soumeth Abasse, Victoria Cacheux, Serge Herson, Christine Fuhrmann, Olivier Proost, Bernard Bedock, Olivier Rogeaux, Mostapha Hajjar, Anne Reverseau, René Courcol, Françoise Carmagnol, Yves Guénard, Céline Ménard, Bouchra Lamia, Bruno Lemmens, Damien Bouhour, L. Lequen, Gaëlle Baty, Cédric Bouet, Dominique Guerrot, Stéphane Blanc, Catherine Chirouze, Anne-Hélène Reboux, A. Vachée, Gregory Taurin, Myriam Mein-Bottini, Jean-Pierre Belot, Alain Lafeuillade, Patricia Gabez-Therou, Philippe Labrousse, Bernard Jarrousse, Philippe Noto, Vincent Brunot, Philippe Condominas, Marion Challier, Béatrice Berçot, Delphine Anuset, Mélanie Daval Cote, François Bernasconi, Y. Costa, Chandrah Goburdhun, Bernard Gressier, Alban Michaud-herbst, Franck Charlier, Moussa Hecham, Luc Boulain, Hélène Corneloup, Alix Greder Belan, Nicolas Boussekey, Claire-Antoinette Dupuy, Yannick Rouquet, Benoit Renard, Benifla Jl, Etienne Javouhey, Michèle Granier, Marie-Christine Jaffarbandjee, Emilie Piet, Benoît Bergues, Claire Malbrunot, Catherine Tiry, Philippe Mérigot, Mouna Ben Soltana, Chantal Roure Sobas, Florian Radenac, Yves Thomas, Agathe Blaise, Sylvie De Martino, Laurence Legout, Gabriel Choukroun, Jean-François Muir, Peggy Dupretz, Patrick Dupont, François Guichart, Julie Jean, Jean-Michel Descamps, Bernard Kittschke, Anne Gruson, Gerard Viquesnel, Marie Keller, Pascal Chavanet, Françis Vallet, Yvan Vaschalde, Jean-Luc Hanouz, Gerard Lina, Françoise Loison, Simon Vincent, Jean-Paul Thellier, Moncef Afi, Dominique Zagozda, Hélène Sokeng-Affoule, Marc Le Bideau, Jean-François Loriferne, Alain Gravet, Sophie Deprecq, Tarik Naceur, Severine Mielczarek, René-Jean Bensadoun, Bernard Karkous, Yves Bléher, Jocelyne Poulain, Véronique Goulet, Laurence Nicolet, Sophie Arista, Antônio Lúcio Teixeira, Jean-François Schved, Laurent Nicolet, Claire Lecomte, Faiza Benddif-Fin, Michel Aumersier, Laurence Burc-Struxiano, Maxime Thouvenin, Samia Harbi, Mathieu Detave, Catherine Rebeyrotte, Jean-Paul Kisterman, Bruno Berdin, Pascal Vincent, Laurent Argaud, Elisabeth Parisi-Duchene, Geneviève Julienne, Fernanda Farto-Bensasson, Georges-Fabrice Blum, Sad Gaizi, Tali-Anne Szwebel, Raphaël Lepeule, Marie-Thérèse Climas, Anne-Françoise Dillies, Amar Boudhane, Umberto Simeoni, Pierre-François Dequin, Gérard Oliviero, Alain Gourlaouen, Caroline Piau, Marie-France Lutz-Murphy, Benoît Claude, Jean-Paul Aubry, Nadine Dubosc-Marchenay, Kamilla Chraibi, Emmanuelle Heusse, Sylvain Le Chevallier, Nathalie Brieu, Farid Sifaoui, Lorraine Letranchant, Hélène Durox, Jean-Pierre Lagasse, Adel Ghedira, Xavier Roubert, Fatma Magdoud, Hélène Jean-Pierre, Etienne Carbonelle, Olivier Dereeper, Lionel Carbillon, Christophe Billy, Mélanie Roblin, Marie-José Kodzin, Philippe Niel, Solène Makdessi, Matteo Vassallo, Maryse Archambaud, Fabian Haccourt, Didier Blaise, Stéphane Bourgeois, Elena Marcu, Charles Kubiak, Brisse Castel, François Guinet, Marie Pouzoullic, Frédérique Nathan-Bonnet, Vincent Gendrin, Céline Becherrawy, Aline Secher, Pierre Abgueguen, Clarence Eloy, Jean-Marc Tourani, Frédéric Klapczynski, Bernard Montmasson, Philippe Real, Joanna Pofelski, Yves Welker, Karim Krechiem, Eric Caumes, Martine Elena-Daumas, Christophe Saigne, Gilles Hittinger, Chantal Delesalle, Jonathan Messika, Fabrice Lesage, Daniela Pop, Daniel Coetmeur, Renato Colamarino, Chetaou Mahaza, Patrick Plésiat, Isabelle Fredenucci, Mylène Baret, Guy Mager, Pascale Chavel, Isabelle Labourdette, Anne-Claude Menguy, Nicolas Fortineau, Ludovic Le Sec, Valérie Gauduchon, Francis Barraud, Nicolas Letellier, Didier Vincent, Janine Frey, Philippe Riegel, Michel Pavic, Jean-Luc Fabre, Jean-Pierre Fauchart, Alain Goudeau, Stéphanie Husson-Wetzel, Philippe Eymerit, Mohamed Camara, Nathalie Seta, Elisabeth Carole Ngo Bell, Philippe Repellin, Laurent Alric, Vincent Leroy, Françoise Delisle Mizon, Jean-Philippe Emond, Marie-Françoise Borie, Lise Crémet, Wladimir Chelle, Elisabeth Brottier-Mancini, Bernard Garrigues, Claire Letellier, Loïc Geffray, Frédéric Méchaï, Julien Bador, Benoit Guery, Alain-Charles Fouilhoux, Corinne Dagada, Pierre Duhaut, Julien Goustille, Arnaud Sément, Francis Carcenac, Isabelle Girard-Buttaz, Claire Chapuzet, Fabienne Jouatte, Bruno Riou, Fabrice Hayoun, Chloé Di Meglio, Youssef Ali, Michel Leneveu, Nathalie Montagne, Yves Garcera, Audrey Moustache, Pierre-Eric Danin, Geneviève Le Lay, Dominique Courouge-Dorcier, Isabelle Worcel, Emmanuel Morelon, Vincent Pestre, Jean-Pierre Vilque, Jean-Christophe Paquet, Lucien Bodson, Anne-Marie Forest, Fabrice Pierre, Christian Pommier, Fabien Dutasta, Pierre Fournel, Stéphanie Courtois, Elodie Dubois, Serge Vanden Einjden, Patrick Honderlick, Pascal Richette, Fabienne Tamion, Véronique Chassy, Richard Megbemado, Anne-Marie Le Reste, Bernard Simian, Henri Osman, Anthony Texier, Badih Ayach, François Simon, Jean-Michel Filloux, Béatrice Dubourdieu, Jean-Claude Semet, Sarah Kubab, Tawfiq Henni, Patrick Dudeffant, Delphine Hequet, Olivier Mimoz, Marc Auburtin, Amélie Chabrol, Mickael Bonnan, Caroline Léonnet, Claire Wintenberger, Serge Ilunga, Patrice Lanba, Sophie Rosello, Alexandre Damage, Flore Bouche, Michel Thibault, Frederic Faibis, Chantal Dhennain, Jean-Philippe Talarmin, Armelle Lamour, Remi Boussier, Fabien Garnier, Marie-Laure Brival, Nourredine Hedjem, Philippe Vande-perre, Raphaël Coint, Jean-Claude Reveil, Eva Weinbronn, Emmanuelle Lavalard, Alexandra Fille, Françoise Le Turdu, Lionel Leroux, Jean-Yves Lefrant, Jean Berthet, Radia Bouaziz, Alain Ravaud, Sylvaine Rousseau, Yacine Merrouche, Alain Le Coustumier, Bertrand Guider, Gisèle Dewulf, Jean-Marc Faucheux, Jacques Piquet, Franck Leibinger, Charles Cerf, Robin Stephan, Jean-Philippe Redonnet, Jean-Paul Stahl, Ella Dzeing, Simona Pavel, Guy Vernet, Ghada Hatem, Samer Kayal, Jacques Deschamps, Dominique Descamps, Marion Levast, Marc Bouiller, Sylvie Dargere, Claire Dingremont, Stéphane Gaudry, François Maillot, Sylvie Odent, Nathalie Cervantes, Hélène Zanaldi, Laurence Gachassin, Olivier Ruyer, David Patin, Benoît Cazenave, Pascal Jacquier, Michelle Boyer, Béatrice Berteaux, Virginie Zarrouk, Jacques Bor, Isabelle Legoff, Hélène Albinet, Florence Rousseau, Gilles Pialoux, Guenaelle Salaun-Beretta, Alexandra Moura, Véronique Vernet Garnier, Didier Lepelletier, Pierre-Alexandre Hauss, Joëlle Belaisch-Amart, Didier Lepeletier, Jacob Xavier, Aline Nare, Annie Motard-Picheloup, Alain Améri, Bertrand Lioger, Jean-Valère Malfuson, Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Référence Listeria - National Reference Center Listeria (CNRL), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Département de Médecine interne [Lariboisière], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Biologie des Infections - Biology of Infection, Service de Gynécologie et Obstétrique [Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Institut Pasteur [Paris] (IP), Infectious Disease Department [Saint Maurice], Agence Nationale de la Santé Publique [Saint-Maurice] (ANSP), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, MONALISA study group, Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency., ROZIER, marie-Claire, CHU Necker - Enfants Malades [AP-HP], Centre National de Référence Listeria - Biologie des Infections (CNRL), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre collaborateur de l'OMS Listeria - Biologie des Infections (CCOMS), CHU Pitié-Salpêtrière [APHP], Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre National de Référence Listeria - Biologie des Infections ( CNRL ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre collaborateur de l'OMS (CCOMS) des Listeria ( CCOMS ), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie ( UPMC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Lariboisière, Biologie des Infections, Institut Pasteur [Paris]-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources ( ICAReB ), Agence Nationale de la Santé Publique [Saint-Maurice] ( ANSP ), Assistance Publique - Hôpitaux de Paris, Assistance publique - Hôpitaux de Paris (AP-HP), Université Paris Descartes - Paris 5 ( UPD5 ), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)
Subjects: Bacteremia/epidemiology/mortality, 0301 basic medicine, Male, Pediatrics, bacteraemia, Infectious Disease Transmission, [SDV]Life Sciences [q-bio], Bacteremia, France/epidemiology, Infant, Newborn, Diseases, Foodborne Diseases, Meningoencephalitis, Pregnancy, Risk Factors, Vertical, Medicine, Listeriosis, Prospective Studies, Pregnancy Complications, Infectious, Prospective cohort study, ddc:618, diabetes, alcoholism, Hazard ratio, Foodborne Diseases/microbiology, immuno suppressive therapies, Prognosis, 3. Good health, [SDV] Life Sciences [q-bio], Hospitalization, Infectious Diseases, isolates, Population Surveillance, Female, France, Listeria monocytogenes/classification/isolation & purification, Cohort study, Adult, medicine.medical_specialty, 030106 microbiology, Notifiable disease, Listeriosis/diagnosis/epidemiology/microbiology, Context (language use), macromolecular substances, 03 medical and health sciences, Humans, study, Aged, [ SDV ] Life Sciences [q-bio], business.industry, Public health, cirrhosis, Infant, Newborn, Infant, Diseases/epidemiology/microbiology, HIV, Mandatory Reporting, Newborn, medicine.disease, Listeria monocytogenes, infection, Infectious Disease Transmission, Vertical, Pregnancy Complications, Infectious/epidemiology/microbiology, Meningoencephalitis/epidemiology/microbiology/mortality, Observational study, business, prognostic, mellitus
Abstract: International audience; Evidence before this study We searched PubMed on June 30, 2016, for English-language cohort studies published since Jan 1, 1980, of patients with invasive listeriosis worldwide with the keywords " listeria " , " listeriosis " , " maternal " , and " neurolisteriosis ". Studies had to include epidemiological or clinical data on listeriosis. All clinical forms of infection were included (bacteraemia, neurolisteriosis, and maternal–neonatal infection). Host risk factors for listeriosis have been well identified, but the clinical features and prognostic factors of the disease are based on retrospective studies compiling heterogeneous data or random collected cases. Furthermore, no clinical trial has ever been done and medical management is not evidence based. Added value of the study Our study is the first prospective clinical study focusing on all forms of invasive listeriosis. The study is based on a national mandatory system that allowed the nearly complete capture of microbiologically proven cases. The study shows a higher burden of listeriosis than reported before: more than 80% of infected mothers experienced major fetal or neonatal complications (fetal loss, very high prematurity, early or late onset disease); only 39% of patients with neurolisteriosis survived and fully recovered. The study provides important new data to improve management and predict outcome in listeriosis, such as determination of the time window for fetal losses (
Published: 2016

42. Liver-infiltrating CD8+ lymphocytes as prognostic factor for tumour recurrence in hepatitis C virus-related hepatocellular carcinoma

Author: Evelyne Jouvin-Marche, Nathalie Sturm, Paulette Bioulac-Sage, Christian Letoublon, Rémy Slama, Vincent Leroy, Jeanne Tran Van Nhieu, Muhammad Ramzan, Jean-Pierre Zarski, Patrice N. Marche, Brigitte Bancel, Philippe Merle, Thomas Decaens, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'anatomie et cythologie pathologique, CHU Grenoble-Hôpital Michallon, Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département de chirurgie digestive et de l'urgence, and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Liver Cirrhosis, Male, 0301 basic medicine, Pathology, Cirrhosis, Survival, analysis, Gene Expression, Kaplan-Meier Estimate, CD8-Positive T-Lymphocytes, Hepatitis, surgery, 0302 clinical medicine, Risk Factors, Recurrence, Tumor Microenvironment, Lymphocytes, Liver Neoplasms, FOXP3, Hepatitis C, Middle Aged, Immunohistochemistry, 3. Good health, medicine.anatomical_structure, Liver, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Female, France, Inflammation Mediators, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Patients, Cells, chemical and pharmacologic phenomena, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Real-Time Polymerase Chain Reaction, Natural killer cell, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, Predictive Value of Tests, Parenchyma, Biomarkers, Tumor, Carcinoma, medicine, Humans, Aged, Inflammation, Hepatology, Perforin, medicine.disease, digestive system diseases, 030104 developmental biology, Neoplasm Recurrence, Local
Abstract: International audience; BACKGROUND: Chronic liver inflammation and immune/inflammatory response promote hepatocellular carcinoma. The aim of this study was to characterize the immune status of HCV-related cirrhosis in patients with hepatocellular carcinoma (HCV-HCC) as compared to HCV patients without hepatocellular carcinoma. METHOD: Immune markers (CD3, CD4, CD8, CD20, CD56, TCRgammadelta, FoxP3) and gene expression profiles (CD8alpha, CD8beta, FoxP3, IL-6, IFN-gamma, perforin, RANTES) were analysed in a test cohort by immunohistochemistry and quantitative RT-PCR analysis on serial non-tumorous and tumorous tissues. RESULTS: Immune micro-environment was more inflammatory in HCV-HCC than HCV cirrhotic livers. The number of CD3(+) , CD4(+) , CD8(+) and CD20(+) liver-infiltrating lymphocytes was significantly higher, whereas the number of CD56(+) cells was significantly lower in HCV-HCC compared to HCV cirrhotic parenchyma. These differences were restricted to fibrous septa for CD4(+) and CD20(+) cells and to nodular parenchyma for CD8(+) cells. Gene expressions of CD8alpha, FoxP3 and RANTES were also significantly higher in HCV-HCC than in HCV cirrhosis. Interestingly, in a large cohort of 63 HCV-HCC patients. The number of CD8(+) cells \\textgreater/=100/field was associated with significant higher tumour recurrence (P = 0.003) and lower overall survival (P = 0.05) at 5 years. CONCLUSION: High densities of liver-infiltrating lymphocytes in HCV-HCC cirrhotic parenchyma prevail inflammatory conditions and could contribute to tumorigenesis and tumour recurrence. These results could contribute towards better clinical evaluation of patients susceptible for HCC recurrence after curative surgery
Published: 2016

43. Nomogram for individualized prediction of hepatocellular carcinoma occurrence in hepatitis C virus cirrhosis (ANRS CO12 CirVir)

Author: Denis Ouzan, Yves Benhamou, Ariane Mallat, Jean-Claude Trinchet, Yannick Bacq, Brigitte Bernard-Chabert, Carole Cagnot, Armand Abergel, Jean-Frédéric Blanc, Victor de Ledinghen, Claire Wartelle, Richard Layese, Christophe Pilette, Vincent Di Martino, Jean-Pierre Bronowicki, Stanislas Pol, Dominique Capron, Nathalie Ganne-Carrié, Philippe Mathurin, Christine Silvain, Marc Bourlière, Ghassan Riachi, Fabien Zoulim, Dominique Guyader, Laurent Alric, Valérie Bourcier, Jean-Didier Grangé, David Zucman, Paul Calès, Albert Tran, Dominique Roulot, Patrick Marcellin, Jean-Pierre Zarski, Françoise Roudot-Thoraval, Thong Dao, Pierre Nahon, Christos Christidis, Lawrence Serfaty, Jean-Marie Péron, Dominique Larrey, Pierre Attali, Génomique Fonctionnelle des Tumeurs Solides ( U1162 ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Jean Verdier, Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), France REcherche Nord & sud Sida-hiv Hépatites (FRENSH), Service d'hépatologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Service des maladies du foie, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Centre Hospitalier Universitaire de Rennes, Foie, métabolismes et cancer, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'hépatologie médicale [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Institut Pasteur [Paris], CHU Saint-Eloi, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut Arnaud Tzanck, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Hôpital Avicenne, CHU Nice, Centre méditérannéen de médecine moléculaire ( C3M ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Hôpital Michallon, Hôpital Charles Nicolle [Rouen], Interactions cellulaires et applications thérapeutiques ( ICAT ), Université d'Angers ( UA ) -CHU Angers-CRLCC Paul Papin-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Pharmacochimie et Pharmacologie Pour le Développement ( PHARMA-DEV ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique ( CNRS ), Service d'Hépato-gastroentérologie, Assistance Publique - Hôpitaux de Marseille ( APHM ), Hôpital Claude Huriez, Hôpital Saint-André, CHU Estaing [Clermont-Ferrand], Service d'hépatologie [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], CHU Henri Mondor, CHU Tenon [APHP], Hôpital Paul Brousse, CHU Trousseau [Tours], CHRU Tours, Hôpital Général Aix en Provence, CHU Caen, CHU Pitié-Salpêtrière [APHP], CHU Le MAns, Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Institut Mutualiste de Montsouris ( IMM ), Centre hospitalier universitaire d'Amiens ( CHU Amiens-Picardie ), CHU Amiens-Picardie, AP-HP Hôpital universitaire Robert-Debré [Paris], Hôpital Foch [Suresnes], Hôpital Jean Minjoz, This study was sponsored by the ANRS (France REcherche Nord & Sud Sida-hiv Hépatites: FRENSH). The funding sponsor had no role in the design or conducting of the study: collection, management, analysis, interpretation of data, nor preparation, review, or approval of the manuscript, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Hôpital Beaujon [AP-HP], CHU Pontchaillou [Rennes], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris] (IP), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Arnault Tzanck, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Hôpital Avicenne [AP-HP], Centre Hospitalier Universitaire de Nice (CHU Nice), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, CHU Rouen, Normandie Université (NU)-Normandie Université (NU), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Hôpital Saint-Joseph [Marseille], Hôpital Claude Huriez [Lille], CHU Lille, CHU Clermont-Ferrand, Service d'hépatologie [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Henri Mondor [Créteil], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier d'Aix en Provence [Aix-en-Provence] (CHIAP ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Le Mans (CH Le Mans), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Mutualiste de Montsouris (IMM), Jonchère, Laurent, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT)
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, education, education.field_of_study, Framingham Risk Score, Hepatology, business.industry, Hazard ratio, Liver Neoplasms, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Hepatitis C, Nomogram, Hepatitis C, Chronic, Middle Aged, medicine.disease, Confidence interval, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Surgery, Nomograms, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, business
Abstract: International audience; Unlabelled - The aim of this work was to develop an individualized score for predicting hepatocellular carcinoma (HCC) in patients with hepatitis C (HCV)-compensated cirrhosis. Among 1,323 patients with HCV cirrhosis enrolled in the French prospective ANRS CO12 CirVir cohort, 720 and 360 were randomly assigned to training and validation sets, respectively. Cox's multivariate model was used to predict HCC, after which a nomogram was computed to assess individualized risk. During follow-up (median, 51.0 months), 103 and 39 patients developed HCC in the training and validation sets, respectively. Five variables were independently associated with occurrence of HCC: age > 50 years (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.16; 3.25; P = 0.012); past excessive alcohol intake (HR, 1.55; 95% CI, 1.02; 2.36; P = 0.041); low platelet count (
Published: 2016

44. Effectiveness and Safety of Tenofovir Disoproxil Fumarate in Chronic Hepatitis B: A 3-Year, Prospective, Real-World Study in France

Author: Fabien Zoulim, Valérie Tilliet, Ghassan Riachi, Dominique Larrey, Christophe Hézode, Pascal Pétour, Denis Ouzan, Patrick Marcellin, Xavier Causse, Jean-Pierre Zarski, Silla M. Consoli, Jean-François Cadranel, Marc Bourlière, Bruno Roche, O. Libert, Christiane Stern, Arnaud Pauwels, Jérôme Dumortier, Régine Truchi, Georges-Philippe Pageaux, Service d'hépatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Arnault Tzanck, Département d'hépatologie, Hospices Civils de Lyon (HCL), Service d'Hépato-gastroentérologie, Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital Charles Nicolle [Rouen], Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Hôpital Européen Georges Pompidou, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Institut Arnaud Tzanck, Hospices Civils de Lyon ( HCL ), Assistance Publique - Hôpitaux de Marseille ( APHM ), Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] ( ICMUB ), Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Male, medicine.medical_specialty, Patients, Physiology, Population, Organophosphonates, HIV Infections, [SDV.CAN]Life Sciences [q-bio]/Cancer, Comorbidity, Pharmacology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Hepatitis, methods, 03 medical and health sciences, Routine practice, 0302 clinical medicine, Internal medicine, medicine, HBV, Humans, 030212 general & internal medicine, Seroconversion, education, Prospective cohort study, Tenofovir, Aged, education.field_of_study, therapy, business.industry, Adenine, Gastroenterology, Dna, Hepatology, Hepatitis B, medicine.disease, 3. Good health, Clinical trial, Real-world, 030211 gastroenterology & hepatology, Original Article, France, history, business, Viral load, Glomerular Filtration Rate
Abstract: International audience; BACKGROUND AND AIMS: Tenofovir disoproxil fumarate (TDF) demonstrated potent and sustainable antiviral efficacy and a good safety profile in patients with chronic hepatitis B (CHB) in controlled clinical trials. Real-world data are important to confirm effectiveness and safety data in patient populations encountered in routine clinical practice. METHODS: This non-interventional, prospective, 36-month study included treatment-naive and treatment-experienced patients with CHB initiating their first TDF regimen (monotherapy or combination therapy) in routine clinical practice in France. Clinical, virologic, biochemical, compliance, and safety data were collected. RESULTS: Data from 440 consecutive patients from 58 centers were analyzed. The majority of the cohort was male (71 %), hepatitis B "e" antigen-negative (HBeAg-) (74 %), and treatment-experienced (56 %); 11 % were aged \textgreater/=65 years; and comorbidities were reported in 39 %. After 12 months, 92 % of the overall cohort achieved virologic response (HBV DNA \textless69 IU/mL) which was maintained to 36 months (96 %); virologic response was achieved by \textgreater90 % of patients irrespective of HBeAg status, age, or prior treatment history. At 36 months, 77 % of patients had normal alanine aminotransferase levels. Fourteen patients lost hepatis B surface (HBs) antigen, and seven seroconverted to anti-HBs. TDF was well tolerated over the 36-month study, including in 14 women who became pregnant during the study. Median estimated glomerular filtration rate did not change markedly from baseline irrespective of prior treatment history. CONCLUSIONS: TDF demonstrated potent virologic and biochemical responses across a broad range of patients reflective of routine clinical practice. The safety profile was consistent with results from pivotal trials
Published: 2016

45. Relative performances of FibroTest, Fibroscan, and biopsy for the assessment of the stage of liver fibrosis in patients with chronic hepatitis C: A step toward the truth in the absence of a gold standard

Author: Thierry, Poynard, Victor, de Ledinghen, Jean Pierre, Zarski, Carol, Stanciu, Mona, Munteanu, Julien, Vergniol, Julie, France, Anca, Trifan, Gilles, Le Naour, Jean Christophe, Vaillant, Vlad, Ratziu, Frederic, Charlotte, and Jean Marie, Castille
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Databases, Factual, Biopsy, Sensitivity and Specificity, Gastroenterology, Internal medicine, medicine, Humans, Stage (cooking), Retrospective Studies, Hepatology, medicine.diagnostic_test, FibroTest, business.industry, Reproducibility of Results, Alanine Transaminase, Hepatitis C, Gold standard (test), Hepatitis C, Chronic, Middle Aged, Reference Standards, Random effects model, medicine.disease, Liver, Liver biopsy, Elasticity Imaging Techniques, Female, business
Abstract: Background & Aims Liver fibrosis stage is traditionally assessed with biopsy, an imperfect gold standard. Two widely used techniques, FibroTest®, and liver stiffness measurement (LSM) using Fibroscan® have been validated using biopsy, and therefore the true performances of these estimates are still unknown in the absence of a perfect reference. The aim was to assess the relative accuracy of FibroTest, LSM, and biopsy using methods without gold standard in patients with chronic hepatitis C (CHC) and controls. Methods A total of 1289 patients with CHC and 604 healthy volunteers, with assessment of fibrosis stage by the three techniques, and alanine aminotransferase (ALT) taken as a control test, were analyzed by latent class method with random effects. In the volunteers, the false positive risk of biopsy was obtained from a large surgical sample of four normal livers. Results The latent class model with random effects permitted to conciliate the observed data and estimates of test performances. For advanced fibrosis, the specificity/sensitivity was for FibroTest 0.93/0.70, LSM 0.96/0.45, ALT 0.79/0.78 and biopsy 0.67/0.63, and for cirrhosis FibroTest 0.87/0.41, LSM 0.93/0.39, ALT 0.78/0.08 and biopsy 0.95/0.51. The analysis of the discordances between pairs suggested that the variability of the model was mainly related to the discordances between biopsy and LSM (residuals>10; p Conclusions A method without the use of a gold standard confirmed the accuracy of FibroTest and Fibroscan for the diagnosis of advanced fibrosis and cirrhosis in patients with chronic hepatitis C. The variability of the model was mostly due to the discordances between Fibroscan and biopsy.
Published: 2012

46. The protease inhibitor, GS-9256, and non-nucleoside polymerase inhibitor tegobuvir alone, with ribavirin, or pegylated interferon plus ribavirin in hepatitis C

Author: Daniel Sereni, David W. Oldach, Michael P. Manns, Steven J. Knox, Yves Horsmans, Christophe Moreno, Jean-Pierre Zarski, Patrick Marcellin, Kosh Agarwal, Peter Buggisch, John G. McHutchison, Sarah Arterburn, Stefan Zeuzem, Hongmei Mo, Hartwig Klinker, and Graham R. Foster
Subjects: Adult, Male, Genotype, Combination therapy, Hepatitis C virus, Hepacivirus, Pharmacology, medicine.disease_cause, Antiviral Agents, Peptides, Cyclic, Polyethylene Glycols, Telaprevir, chemistry.chemical_compound, Pegylated interferon, Ribavirin, medicine, Humans, Protease Inhibitors, Protease inhibitor (pharmacology), Enzyme Inhibitors, NS3, Dose-Response Relationship, Drug, Hepatology, business.industry, Interferon-alpha, Hepatitis C, Middle Aged, medicine.disease, Phosphinic Acids, Recombinant Proteins, Pyridazines, Treatment Outcome, chemistry, Purines, RNA, Viral, Drug Therapy, Combination, Female, business, medicine.drug
Abstract: Tegobuvir (GS-9190), a non-nucleoside nonstructural protein (NS)5B polymerase inhibitor, and GS-9256, an NS3 serine protease inhibitor, individually have activity against hepatitis C virus (HCV) genotype 1. The antiviral activity of tegobuvir and GS-9256 as oral combination therapy, or together with ribavirin (RBV) or pegylated interferon (Peg-IFN) alpha-2a and RBV, was assessed in a phase II, randomized, open-label trial. Treatment-naïve patients with genotype 1 HCV were assigned 28 days of tegobuvir 40 mg twice-daily (BID) and GS-9256 75 mg BID (n = 16), tegobuvir and GS-9256 plus RBV 1,000-1,200 mg daily (n = 15), or tegobuvir and GS-9256 plus Peg-IFN alpha-2a (180 μg once-weekly)/RBV (n = 15). The primary efficacy endpoint was rapid virologic response (RVR), with HCV RNA25 IU/mL at day 28. After 28 days, all patients received Peg-IFN/RBV. All patients with viral rebound or nonresponse, defined as0.5-log(10) increase in HCV RNA from nadir or2-log decrease at day 5, initiated Peg-IFN/RBV immediately. Median maximal reductions in HCV RNA were -4.1 log(10) IU/mL for tegobuvir/GS-9256, -5.1 log(10) IU/mL for tegobuvir/GS-9256/RBV, and -5.7 log(10) IU/mL for tegobuvir/9256/Peg-IFN/RBV. RVR was observed in 7% (1 of 15) of patients receiving tegobuvir/GS-9256, 38% (5 of 13) receiving tegobuvir/GS-9256/RBV, and 100% (14 of 14) receiving tegobuvir/9256/PEG-IFN/RBV. The addition of Peg-IFN/RBV at day 28 or earlier resulted in HCV RNA25 IU/mL at week 24 in 67% (10 of 15), 100% (13 of 13), and 94% (13 of 14) of patients in the three treatment groups. Transient elevations in serum bilirubin occurred in all treatment groups.In genotype 1 HCV, adding RBV or RBV with Peg-IFN provides additive antiviral activity to combination therapy with tegobuvir and GS-9256.
Published: 2012

47. FibroTest® and Fibroscan® performances revisited in patients with chronic hepatitis C. Impact of the spectrum effect and the applicability rate

Author: Thierry Poynard, Victor de Ledinghen, Jean-Pierre Zarski, Carol Stanciu, Mona Munteanu, Julien Vergniol, Julie France, Anca Trifan, Joseph Moussalli, Pascal Lebray, Dominique Thabut, and Vlad Ratziu
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Pathology, Cirrhosis, Population, Gastroenterology, Chronic hepatitis, Internal medicine, medicine, Humans, In patient, Prospective Studies, Prospective cohort study, education, education.field_of_study, Hepatology, business.industry, FibroTest, Significant difference, Reproducibility of Results, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, Elasticity Imaging Techniques, Female, business
Abstract: Two widely used biomarkers of fibrosis, FibroTest and liver stiffness measurement (LSM), have been mostly validated in patients with chronic hepatitis C (CHC) using the standard area under the ROC curve (sAUROC) which is not the most appropriate method due to the risk of fibrosis spectrum effect. Furthermore the performance of these biomarkers have not been assessed in "intention to diagnose" which takes into account the failures and non-reliable results.The aim was to compare the accuracy of FibroTest and LSM for the diagnosis of fibrosis using sAUROC, the pairwise comparison of fibrosis stages by Obuchowski measure (wAUROC), and these AUROCs reassessed after taking into account the applicability rates.One thousand two hundred and eighty-nine patients with CHC and 604 healthy volunteers were analyzed. The performances of biomarkers assessed were compared in a patients-only group (P1: n=1289), in a population combining both patients and healthy volunteers (P2: n=1893) and in a simulated population (P3: n=1893) with the prevalence of stages observed in a reference population, to demonstrate the impact of spectrum effect. Applicability rates were estimated prospectively in 24,872 consecutive FibroTest and in 13,669 consecutive LSM examinations.Using wAUROC, the conclusions of studies with reliable results in P1 were different than in those of P2 and in P3. There was a lower performance of FibroTest versus LSM in P1 (0.864 [0.855-0.873] vs. 0.883 [0.874-0.892]; P=0.002) which was not found in P2 (0.893 [0.887-0.900] vs. 0.894 [0.887-0.901]; P=0.86) and in P3 (0.899 [0.893-0.905] vs 0.902 [0.895-0.909]; P=0.60). Using the sAUROC, in P1, P2 and P3, there was no significant difference between FibroTest and LSM performance for advanced fibrosis and a lower performance of FibroTest versus LSM for cirrhosis. In intention to diagnose, using wAUROCs performances were higher for FibroTest vs. LSM in P1 (0.857 [0.848-0.866] vs. 0.814 [0.807-0.821]; P0.0001) and P2 (0.885 [0.879-0.892] vs. 0.743 [0.737-0.749]; P0.0001), without difference in P3 (0.891 [0.885-0.897] vs. 0.894 [0.887-0.901]; P=0.90). Using sAUROC, the significant differences in favor of FibroTest vs LSM persisted also for the diagnosis of advanced fibrosis, both in P1 and P2 (P0.0001) and for the diagnosis of cirrhosis in P1 (P0.001).When the spectrum effects and applicability rates were taken into account, LSM had lower performance results than FibroTest for the diagnosis of fibrosis stages.
Published: 2011

48. Fibrosis progression under maintenance interferon in hepatitis C is better detected by blood test than liver morphometry

Author: J. Marc Chapplain, Sandrine Bertrais, Jean-Pierre Zarski, Julien Chaigneau, M. Eddine Charaf, Paul Calès, Gérard Babany, Nathalie Sturm, and Christian Michelet
Subjects: METAVIR Fibrosis Score, Pathology, medicine.medical_specialty, Population, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Virology, Internal medicine, Biopsy, medicine, Blood test, education, 030304 developmental biology, 0303 health sciences, education.field_of_study, Hepatology, medicine.diagnostic_test, business.industry, Hepatitis C, medicine.disease, 3. Good health, Infectious Diseases, Liver biopsy, 030211 gastroenterology & hepatology, Hepatic fibrosis, business
Abstract: We evaluated whether quantitative measurements of liver fibrosis with recently developed diagnostics outperform histological staging in detecting natural or interferon-induced changes. We compared Metavir staging, morphometry (area and fractal dimension) and six blood tests in 157 patients with chronic hepatitis C from two trials testing maintenance interferon for 96 weeks. Paired liver biopsies and blood tests were available for 101 patients, and there was a significant improvement in Metavir activity and a significant increase in blood tests reflecting fibrosis quantity in patients treated with interferon when compared with controls - all per cent changes in histological fibrosis measures were significantly increased in F1 vs F2-4 stages only in the interferon group. For the whole population studied between weeks 0 and 96, there was significant progression only in the area of fibrosis (AOF) (P = 0.026), FibroMeter (P = 0.020) and CirrhoMeter (P = 0.003). With regards to dynamic reproducibility, agreement was good (r(ic) ≥ 0.72) only for Metavir fibrosis score, FibroMeter and CirrhoMeter. The per cent change in AOF was significantly higher than that of fractal dimension (P = 0.003) or Metavir fibrosis score (P = 0.015). CirrhoMeter was the only blood test with a change significantly higher than that of AOF (P = 0.039). AOF and two blood tests, reflecting fibrosis quantity, have high sensitivity and/or reproducibility permitting the detection of a small progression in liver fibrosis over two years. A blood test reflecting fibrosis quantity is more sensitive and reproducible than morphometry. The study also shows that maintenance interferon does not improve fibrosis, whatever its stage.
Published: 2011

49. Injection drug use before and after liver transplantation: a retrospective multicenter analysis on incidence and outcome

Author: Jean-Pierre Zarski, Vincent Leroy, Andrea De Gottardi, Vincenzo La Mura, Darius Moradpour, Gilles Mentha, Emiliano Giostra, Olivier Boillot, Marie Noelle Hilleret, Antoine Hadengue, P. Gelez, Olivier Guillaud, Jérôme Dumortier, Pietro Majno, Philippe Morel, and Massimiliano Fontana
Subjects: Transplantation, medicine.medical_specialty, Alcoholic liver disease, education.field_of_study, Cirrhosis, business.industry, Incidence (epidemiology), medicine.medical_treatment, Population, Retrospective cohort study, Liver transplantation, medicine.disease, Surgery, Internal medicine, Epidemiology, medicine, education, business
Abstract: BACKGROUND AND AIMS: Injecting drug use (IDU) before and after liver transplantation (LT) is poorly described. The aim of this study was to quantify relapse and survival in this population and to describe the causes of mortality after LT. METHODS: Past injection drug users were identified from the LT listing protocols from four centers in Switzerland and France. Data on survival and relapse were collected and used for uni- and multivariate analysis. RESULTS: Between 1988 and 2006, we identified 59 patients with a past history of IDU. The mean age at transplantation was 42.4 yr and the majority of patients were men (84.7%). The indication for LT was for the vast majority viral cirrhosis accounting for 91.5% of cases, while alcoholic cirrhosis was 5.1%. There were 16.9% of patients who had a substitution therapy before and 6.8% who continued after LT. Two patients (3.4%) relapsed into IDU after LT and died at 18 and 41 months. The mean follow-up was 51 months. Overall survival was 84%, 66%, and 61% at 1, 5, and 10 yr after transplantation. CONCLUSIONS: Documented IDU was rare in liver transplanted patients. Past IDU was not associated with poorer survival after LT, and relapse after LT occurred in 3.4%.
Published: 2010

50. Non-invasive assessment of liver fibrosis progression in hepatitis C patients retreated for 96 weeks with antiviral therapy: a randomized study

Author: Gérard Babany, P. Melin, A Pinta, Michèle Chevallier, Jean-Pierre Zarski, Nathalie Sturm, Corinne Bonny, Philippe Sogni, Stéphanie Rouanet, Alice Cheveau, Hervé Desmorat, and J.-J. Raabe
Subjects: METAVIR Fibrosis Score, medicine.medical_specialty, Pathology, Hepatology, medicine.diagnostic_test, business.industry, Hepatitis C, medicine.disease, Gastroenterology, Maintenance therapy, Fibrosis, Internal medicine, Predictive value of tests, Biopsy, medicine, Clinical endpoint, Hepatic fibrosis, business
Abstract: Background The efficacy of a maintenance therapy in non-responder patients with chronic hepatitis C has been essentially evaluated by histological semiquantitative scores. Aim The aim was to evaluate the efficiency of 2 years of treatment with peginterferon alpha-2a vs alpha-tocopherol in these patients by histology, morphometry and blood markers of fibrosis. Method Hundred and five HCV patients with a Metavir fibrosis score > or = 2 were randomized to receive peginterferon alpha-2a 180 microg/week (PEG) (n=55) or alpha-tocopherol (TOCO) 1000 mg/day (n=50) for 96 weeks. The primary endpoint was improvement or stabilization of the Metavir fibrosis score by biopsy performed at week 96. Secondary endpoints included a quantitative assessment of fibrosis by morphometry and changes in blood markers of fibrosis. Results There was no difference at baseline between PEG and TOCO according to the metavir (83.3 vs 86.8%, P=0.751) stage. The median fibrosis rate, measured with morphometry was 2.72 and 2.86% at day 0, and 3.66 and 2.82% at week 96, in the PEG and TOCO groups (P=0.90) respectively. However, the percentage of patients with metavir activity grade improvement was significantly higher in the PEG group vs the TOCO group (52.8 vs 23.7%, P=0.016). Non-invasive markers analysis did not show any significant change in both groups. Conclusion Long-term therapy with peginterferon alpha-2a did not reduce liver fibrosis degree assessed by morphometry and blood tests as compared with alpha-tocopherol. Blood tests could be useful to assess liver fibrosis changes in clinical trials.
Published: 2010

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