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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. 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

3. Management of peripheral vertigo with antihistamines: New options on the horizon

Author: Jonas Dyhrfjeld-Johnsen and Pierre Attali
Subjects: medicine.medical_specialty, Side effect, Sedation, medicine.medical_treatment, Histamine Antagonists, Reviews, Peripheral vertigo, 030226 pharmacology & pharmacy, Histamine Agonists, 03 medical and health sciences, 0302 clinical medicine, Vertigo, otorhinolaryngologic diseases, medicine, Animals, Humans, Pharmacology (medical), Betahistine, 030212 general & internal medicine, Intensive care medicine, Aged, Receptors, Histamine H4, Pharmacology, Vestibular system, biology, business.industry, Behavioural intervention, biology.organism_classification, Pyrimidines, Azetidines, Antihistamine, sense organs, medicine.symptom, business, medicine.drug
Abstract: Vertigo is associated with a wide range of vestibular pathologies. It increasingly affects the elderly, with a high cost to society. Solutions include vestibular suppressants and vestibular rehabilitation, which form the mainstay of therapy. Antihistamines represent the largest class of agents used to combat vestibular vertigo symptoms. Agents targeting the H(1) and H(3) receptors have been in clinical use for several decades as single agents. Nonetheless, effective management of vertigo proves elusive as many treatments largely address only associated symptoms, and with questionable efficacy. Additionally, the primary and limiting side effect of sedation is counterproductive to normal functioning and the natural recovery process occurring via central compensation. To address these issues, the timing of administration of betahistine, the mainstay H(3) antihistamine, can be fine‐tuned, while bioavailability is also being improved. Other approaches include antihistamine combination studies, devices, physical therapy and behavioural interventions. Recently demonstrated expression of H(4) receptors in the peripheral vestibular system represents a new potential drug target for treating vestibular disorders. A number of novel selective H(4) antagonists are active in vestibular models in vivo. The preclinical potential of SENS‐111 (Seliforant), an oral first‐in‐class selective H(4) antagonist is the only such molecule to date to be translated into the clinical setting. With an excellent safety profile and notable absence of sedation, encouraging outcomes in an induced vertigo model in healthy volunteers have led to ongoing clinical studies in acute unilateral vestibulopathy, with the hope that H(4) antagonists will offer new effective therapeutic options to patients suffering from vertigo.
Published: 2019

4. 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

5. 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

6. 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

7. Safety, tolerability, pharmacokinetics and pharmacokinetic-pharmacodynamic modelling of the novel H4receptor inhibitor SENS-111 using a modified caloric test in healthy subjects

Author: Frédéric Venail, Sonia Poli, Eric Wersinger, Sébastien Schmerber, Roberto Gomeni, and Pierre Attali
Subjects: Pharmacology, education.field_of_study, biology, business.industry, Sedation, Population, Antagonist, Nystagmus, biology.organism_classification, 030226 pharmacology & pharmacy, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Pharmacodynamics, Vertigo, Medicine, Distribution (pharmacology), Pharmacology (medical), medicine.symptom, business, education, 030217 neurology & neurosurgery
Abstract: AIM: A Phase 1 study was performed to evaluate safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the selective histamine H4 receptor antagonist SENS-111, an oral small molecule. METHODS: One hundred healthy subjects were randomized in a placebo-controlled, double-blind study evaluating single-ascending doses (SAD; 100-500 mg) and multiple-ascending doses (MAD; 50-150 mg day-1 , 4 days; 200-250 mg day-1 , 7 days). Effects of SENS-111 on nystagmus and vertigo induced by modified caloric tests were measured in the MAD studies. Population PK and PK/PD models were developed using a nonlinear mixed-effects approach. RESULTS: SENS-111 was well tolerated with mild to moderate events. No sedation was reported. A maximal tolerated dose was not reached. Dose-proportional increases in concentrations were seen up to 200 mg and more than dose-proportional thereafter, with mean half-life between 24 and 56 h. The caloric test induced mild but measurable vertigo and nystagmus with large intra/inter-individual variation for all parameters. SENS-111 did not significantly impact nystagmus but significantly improved latency of vertigo appearance/disappearance, duration and European Evaluation of Vertigo questionnaire parameters vs. baseline. A two-compartment model with first-order absorption, distribution and elimination best fit the data. PK/PD indirect modelling applied to vertigo duration and latency of appearance indicated maximum activity between 100 and 500 ng ml-1 plasma concentrations, corresponding to 100 and 200 mg day-1 , which are appropriate for clinical efficacy evaluations in vestibular diseases. CONCLUSIONS: SENS-111 is a well-tolerated first-in-class H4 receptor antagonist with acceptable PK for oral daily dosing. PK/PD modelling determined plasma concentrations and doses for efficacy studies in patients with vertigo symptoms.
Published: 2018

8. 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

9. 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

10. Gene therapy for patients with advanced solid tumors: a phase I study using gene electrotransfer to muscle with the integrin inhibitor plasmid AMEP

Author: Iben Spanggaard, Pierre Attali, Helle W. Hendel, Céline Bouquet, Julie Gehl, Helle Hjorth Johannesen, Line Laessoee, Rasmus Hvass Hansen, and Karin Dahlstroem
Subjects: Adult, Male, 0301 basic medicine, Transfer DNA, Integrins, Genetic enhancement, Angiogenesis Inhibitors, Gene electrotransfer, 03 medical and health sciences, 0302 clinical medicine, Plasmid, Pharmacokinetics, Neoplasms, medicine, Humans, Tissue Distribution, Radiology, Nuclear Medicine and imaging, Muscle, Skeletal, Aged, medicine.diagnostic_test, business.industry, Membrane Proteins, Skeletal muscle, Magnetic resonance imaging, Genetic Therapy, Hematology, General Medicine, Middle Aged, Prognosis, Molecular biology, ADAM Proteins, Electroporation, 030104 developmental biology, Real-time polymerase chain reaction, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Cancer research, Female, business, Follow-Up Studies, Plasmids
Abstract: Background: Gene electrotrotransfer describes the use of electric pulses to transfer DNA to cells. Particularly skeletal muscle has potential for systemic secretion of therapeutic proteins. Gene electrotransfer to muscle using the integrin inhibitor plasmid AMEP (Antiangiogenic MEtargidin Peptide) was investigated in a phase I dose escalation study. Primary objective was safety. Material and methods: Patients with metastatic or locally advanced solid tumors, without further standard treatments available, were treated with once-only gene electrotransfer of plasmid AMEP to the femoral muscle. Safety was monitored by adverse events registration, visual analog scale (VAS) after procedure and magnetic resonance imaging (MRI) of treated muscles. Pharmacokinetics of plasmid AMEP in plasma and urine was determined by quantitative polymerase chain reaction. Response was evaluated by positron emission tomography–computed tomography (PET–CT) scans. Results: Seven patients were enrolled and treated at dose levels from 50 to 250 μg of plasmid AMEP, the study was terminated early due to cessation of plasmid production. Minimal systemic toxicity was observed and only transient mild pain was associated with the delivery of the electric pulses. MRI of the treated muscles revealed discrete intramuscular edema 24 h after treatment. The changes in the muscle tissue resolved within 2 weeks after treatment. Peak concentrations of plasmid AMEP was detected only in plasma within the first 24 hours after injection. Protein AMEP could not be detected, which could be due to the limit of detection. No objective responses were seen. Conclusions: Gene electrotransfer of plasmid AMEP was found to be safe and tolerable. No objective responses were observed but other DNA drugs may be tested in the future using this procedure.
Published: 2017

11. 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

12. 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

13. 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

14. 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

15. 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

16. Doxorubicin-Loaded Nanoparticles for Patients with Advanced Hepatocellular Carcinoma after Failure of Sorafenib: RELIVE, a Phase-3 Trial

Author: Henning Wege, François Habersetzer, Carine Richou, Jean-Pierre Bronowicki, Jean-Marc Phelip, G. Pelletier, Eric Nguyen Khac, Armand Abergel, Imam Waked, Audrey Molé, Relive Investigators, Julie Le Boulicaut, Andrea Casadei Gardini, Bérangère Vasseur, Nelson S. Yee, Albert Tran, Ivan Borbath, Philippe Merle, Jean-Frédéric Blanc, Massimo Gaetano Colombo, G.-P. Pageaux, Amr S Saad, René Gerolami, Yann Touchefeu, and Pierre Attali
Subjects: Sorafenib, education.field_of_study, medicine.medical_specialty, Performance status, business.industry, Population, Hazard ratio, Neutropenia, medicine.disease, Discontinuation, Internal medicine, medicine, Clinical endpoint, Adverse effect, education, business, medicine.drug
Abstract: Background: Cytotoxic chemotherapy is generally ineffective in patients with hepatocellular carcinoma (HCC). We evaluated the intravenous perfusion of doxorubicin-loaded nanoparticles (DT) in HCC patients with prior failure of sorafenib therapy. Methods: We conducted a randomized, open label, 3 parallel groups, phase-3 trial at 70 sites in 11 countries. Patients with HCC with prior one or more systemic therapies including sorafenib were randomised 1:1:1 for DT-30 mg/m2 (DT-30), DT-20 mg/m2 (DT-20) or best standard of care (BSC); stratified by performance status, Child-Pugh score, DT dosage, macrovascular invasion, extrahepatic spread, alpha-fetoprotein level, number of prior systemic lines, reason of sorafenib discontinuation, and aetiology of HCC. The primary endpoint was overall survival. This trial is registered at ClinicalTrials.gov, number NCT01655693. Findings: Between June 2012 and January 2017, 541 patients were screened, 397 randomized (DT-30=133; DT-20=130; BSC=134; population for efficacy analysis), and 376 initiated treatments (DT-30=120; DT-20=122; BSC=134; population for safety analysis). After pooling the DT-30 and DT-20 arms in the analysis, pooled DT (pDT) did not improve overall survival with a hazard ratio of 1.00 (95% CI 0.78-1.28; p=0.99); median overall survival (95%CI) was 9.1 months (8.1-10.4) for pDT versus 9.0 months (7.1-11·8) for BSC. The hazard ratio for progression-free survival was 0.95 (95% CI 0.74-1.22; p=0.70) and for time to progression 0.96 (95%CI 0.74-1.23; p=0.74). Adverse events were reported in 94% (247/263) of pDT and 75% (100/134) of BSC. The most common grade 3 or 4 treatment-emergent adverse events included (pDT; BSC) neutropenia (8% [20/242]; 5% [6/134]), asthenia (3% [6/242]; 3% [4/134]), and thrombocytopenia (1% [3/242]; 7% [9/134]). Rates of drug-related death per investigators were 1% (3/242; pDT) and 1% (2/193; BSC). Interpretation: DT doesn't show benefit on survival in HCC patients with failure on prior sorafenib treatment, but it has a comforting safety profile. Trial Registration Number: ClinicalTrials.gov, number NCT01655693 Funding: ONXEO Conflict of Interest: PM has received consultancy and advisory fees from Onxeo, Bayer, Lilly, Ipsen, BMS, and MSD. JFB has received consultancy and advisory fees from Onxeo, Bayer, Lilly, Ipsen, and BMS. JPB has received consultancy and advisory fees from Onxeo, and Bayer. GP has received consultancy and advisory fees from Bayer, AbbVie, Novartis, and Gilead. AA has received consultancy and advisory fees from AbbVie, MSD, and Gilead. IW has received consultancy and advisory fees from Janssen, AbbVie, MSD, Marcyrl, Pharco, and Gilead. NY has received consultancy and advisory fees from Halozyme, Boston Biomedical Inc., Pharmacyclics, EMD Serono, Merck, Onxeo, Regeneron, and Momenta. Ethical Approval: The trial was approved by each centre’s ethics committee or institutional review board and complied with Good Clinical Practice guidelines, the Declaration of Helsinki, and applicable local laws.
Published: 2018

17. 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

18. Effect on HBs antigen clearance of addition of pegylated interferon alfa-2a to nucleos(t)ide analogue therapy versus nucleos(t)ide analogue therapy alone in patients with HBe antigen-negative chronic hepatitis B and sustained undetectable plasma hepatitis B virus DNA: a randomised, controlled, open-label trial

Author: Fabien Zoulim, Jean-Michel Molina, Laurent Alric, Isabelle Rosa, Magali Picon, Magali Bouvier-Alias, Pascaline Rabiega, Pierre Attali, Yannick Bacq, Patrizia Carrieri, Dominique Thabut, Marc Bourlière, Albert Tran, Vincent Leroy, Inga Bertucci, Fabrice Carrat, Christophe Hézode, Jean-Pierre Bronowicki, Dominique Guyader, Jean-Didier Grangé, Yoann Barthe, Nathalie Ganne-Carrié, Patrick Marcellin, Xavier Causse, Ghassan Riachi, Lawrence Serfaty, Hélène Fontaine, Hôpital Saint-Joseph [Marseille], 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), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hépatologie [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'hépatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], 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), CHU Pontchaillou [Rennes], 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), Centre Hospitalier du Pays d'Aix, Centre Hospitalier Régional d'Orléans (CHRO), 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), Centre Hospitalier Universitaire de Nancy (CHU Nancy), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Hôpital Charles Nicolle [Rouen], CHI Créteil, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de maladies infectieuses et tropicales [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), 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'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), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), 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), ANRS France Recherche Nord & sud Sida-hiv hépatites, 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), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hépato-gastroentérologie, Assistance Publique - Hôpitaux de Marseille (APHM), 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 [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Saint-Antoine [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Paul Brousse, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), 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), CHU Saint-Antoine [APHP], 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), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], 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 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 [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), 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, Male, Serum, HBsAg, analysis, medicine.disease_cause, Gastroenterology, Polyethylene Glycols, Hepatitis, 0302 clinical medicine, Pegylated interferon, Pregnancy, Hepatitis B e Antigens, Nucleotides, Nucleosides, Hepatitis B, Middle Aged, Recombinant Proteins, 3. Good health, Intention to Treat Analysis, HBeAg, Hepatocellular carcinoma, Medicine, 030211 gastroenterology & hepatology, Female, France, medicine.drug, Adult, medicine.medical_specialty, Hepatitis B virus, Adolescent, Patients, contraindications, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antiviral Agents, Drug Administration Schedule, Time, Injections, methods, 03 medical and health sciences, Young Adult, Hepatitis B, Chronic, Internal medicine, medicine, Humans, Patient Reported Outcome Measures, Aged, therapy, Hepatitis B Surface Antigens, Hepatology, business.industry, Carcinoma, Interferon-alpha, Dna, medicine.disease, Regimen, 030104 developmental biology, Immunology, DNA, Viral, business
Abstract: International audience; BACKGROUND: Findings from uncontrolled studies suggest that addition of pegylated interferon in patients with HBe antigen (HBeAg)-negative chronic hepatitis B receiving nucleos(t)ide analogues with undetectable plasma hepatitis B virus (HBV) DNA might increase HBs antigen (HBsAg) clearance. We aimed to assess this strategy. METHODS: In this randomised, controlled, open-label trial, we enrolled patients aged 18-75 years with HBeAg-negative chronic hepatitis B and documented negative HBV DNA while on stable nucleos(t)ide analogue regimens for at least 1 year from 30 hepatology tertiary care wards in France. Patients had to have an alanine aminotransferase concentration of less than or equal to five times the upper normal range, no hepatocellular carcinoma, and a serum alpha fetoprotein concentration of less than 50 ng/mL, normal dilated fundus oculi examination, and a negative pregnancy test in women. Patients with contraindications to pegylated interferon were not eligible. A centralised randomisation used computer-generated lists of random permuted blocks of four with stratification by HBsAg titres (\textless or \textgreater/=2.25 log10 IU/mL) to allocate patients (1:1) to receive a 48 week course of subcutaneous injections of 180 mug per week of pegylated interferon alfa-2a in addition to the nucleos(t)ide analogue regimen or to continue to receive nucleos(t)ide analogues only. The primary endpoint was HBsAg loss at week 96 by intention-to-treat analysis. This trial is closed and registered with ClinicalTrials.gov, number NCT01172392. FINDINGS: Between Jan 20, 2011, and July 18, 2012, we randomly allocated 185 patients (92 [50%] to pegylated interferon and nucleos(t)ide analogues and 93 [50%] to nucleos(t)ide analogues alone). We excluded two patients from the pegylated interferon plus nucleos(t)ide analogues group from analyses because of withdrawal of consent (one patient) or violation of inclusion criteria (one patient). At week 96, loss of HBsAg was reported in seven (7.8%) of 90 patients in the pegylated interferon plus nucleos(t)ide analogues group versus three (3.2%) of 93 in the nucleos(t)ide analogues-alone group (difference 4.6% [95% CI -2.6 to 12.5]; p=0.15). 85 (94%) of 90 patients started pegylated interferon, three (4%) of whom had a dose reduction and 17 (20%) had an early discontinuation of pegylated interferon (seven [41%] for serious adverse events). Grade 3 and 4 adverse events were more frequent in the pegylated interferon plus nucleos(t)ide analogues group (26 [29%] grade 3 adverse events; 19 [21%] grade 4 adverse events) than in the nucleos(t)ide analogues-alone group (three [3%] grade 3; six [6%] grade 4). INTERPRETATION: Addition of a 48 week course of pegylated interferon to nucleos(t)ide analogue therapy in patients with HBeAg-negative chronic hepatitis B with undetectable HBV DNA for a least 1 year was poorly tolerated and did not result in a significant increase of HBsAg clearance. FUNDING: Institut national de la sante et de la recherche medicale-Agence nationale de recherches sur le sida et les hepatites virales (France Recherche Nord&sud Sida-vih Hepatites)
Published: 2017

19. 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

20. 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

21. Randomized, Comparative, Double-Blind, Double-Dummy, Multicenter Trial of Miconazole Buccal Tablet and Clotrimazole Troches for the Treatment of Oropharyngeal Candidiasis: Study of Miconazole Lauriad®Efficacy and Safety (SMiLES)

Author: Pierre Attali, Zoja Noveljic, Andrei Barasch, Jose A. Vazquez, Ismail Mitha, Jan Fourie, Joel B. Epstein, Brian Conway, Padaruth Ramlachan, Lauren L. Patton, and Rajesh V. Lalla
Subjects: Adult, Male, medicine.medical_specialty, Antifungal Agents, Miconazole, Opportunistic infection, Administration, Oral, HIV Infections, Oropharyngeal Candidiasis, law.invention, Double-Blind Method, Randomized controlled trial, Candidiasis, Oral, law, Internal medicine, Multicenter trial, medicine, Humans, Pharmacology (medical), Clotrimazole, Candida, chemistry.chemical_classification, Chi-Square Distribution, AIDS-Related Opportunistic Infections, business.industry, Administration, Buccal, HIV, Buccal administration, medicine.disease, Surgery, Infectious Diseases, chemistry, Patient Compliance, Azole, Female, business, medicine.drug
Abstract: Oropharyngeal candidiasis (OPC) is the most common opportunistic infection among persons infected with human immunodeficiency virus (HIV). Once-daily miconazole 50 mg buccal tablet (MBT) is a novel delivery system using an extended-spectrum azole with potent in vitro activity against many Candida species, including some that may be resistant to other azoles.This phase 3, double-blind, double-dummy, multicenter trial evaluated 578 randomized patients with HIV infection and OPC. The study compared the efficacy and safety of MBT once daily with clotrimazole 10 mg troches (CT) 5 times daily for 14 days. The co-primary efficacy endpoints were clinical cure at test of cure (TOC) visit (days 17-22) in the intent-to-treat (ITT) and per protocol (PP) populations.Clinical cure rate at TOC visit for MBT-treated patients was statistically noninferior to CT-treated patients in both the ITT (61% vs 65%) and PP (68% vs 74%) populations. Secondary endpoints, safety, and tolerability were similar between treatment groups.In this large trial, once-daily MBT was shown to be noninferior to CT 5 times daily in the treatment of OPC in HIV-positive patients. MBT offers an effective, safe, and well-tolerated topical treatment option for OPC administered as a convenient once-daily dose.
Published: 2010

22. Fast-track HCV check-up enhances possibility of sustained virologicalresponse in HCV infected patients

Author: Teresa Antonini, E. De Martin, A.-M. Roque-Afonso, Rodolphe Sobesky, Mariagrazia Tateo, Audrey Coilly, Jean Charles Duclos-Vallée, Bruno Roche, Didier Samuel, and Pierre Attali
Subjects: Hepatology, business.industry, Medicine, Fast track, business, Virology
Published: 2018

23. O112 : HBsAg clearance after addition of 48 weeks of pegifn in HBeAg negative CHB patients on nucleos(T)ide therapy with undetectable hbvdna for at least one year: final results from ANRS-HB06 pegan study: multicenter randomized controlled phase III trial

Author: Maurice Picon, Yannick Bacq, Jean-Didier Grangé, Hélène Fontaine, Pierre Attali, Christophe Hézode, Patrick Marcellin, Dominique Guyader, Inga Bertucci, Fabrice Carrat, Magali Bouvier-Alias, Vincent Leroy, Jean-Michel Molina, Lawrence Serfaty, M. Bourlière, Nathalie Ganne-Carrié, Jean-Pierre Bronowicki, A. Tran, N. Pouget, Xavier Causse, Isabelle Rosa, Yves Benhamou, Ghassan Riachi, Pascaline Rabiega, Fabien Zoulim, Service d'Hépato-gastroentérologie, Assistance Publique - Hôpitaux de Marseille (APHM), Service d'hépatologie [Saint-Antoine], CHU Saint-Antoine [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'hépatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Laboratoire de microbiologie et génétique moléculaires (LMGM), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie et de biologie structurale (IPBS), Service des maladies du foie, Centre Hospitalier Universitaire [Rennes]-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, 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'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Epidémiologie, Systèmes dínformation et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [APHP], 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), 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 Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Centre Hospitalier Universitaire [Rennes], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-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-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ESIM - Déterminants Sociaux de la Santé et du Recours aux Soins (DS3), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de microbiologie et génétique moléculaires - UMR5100 (LMGM), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Service des maladies du foie [CHU Rennes], Centre Hospitalier Universitaire [Rennes], 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 ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Service d'hépatologie [CHU Saint-Antoine]
Subjects: medicine.medical_specialty, HBsAg, Hepatology, business.industry, [SDV]Life Sciences [q-bio], Gastroenterology, Virology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Hbeag negative, Internal medicine, medicine, 030211 gastroenterology & hepatology, 030212 general & internal medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; no abstract
Published: 2015

24. P0768 : Late mortality in treatment-experienced cirrhotic patients treated with triple therapy including boceprevir or telaprevir in a real-life cohort - ANRS Co 20 cupic

Author: Stanislas Pol, Dominique Larrey, Hélène Fontaine, Valérie Canva, A. Tran, Christophe Hézode, Armando Abergel, Yoann Barthe, Laurent Alric, Thong Dao, Pierre Attali, J.-M. Pawlotsky, Damien Lucidarme, Didier Samuel, Patrice Cacoub, S. Metivier, Thierry Poynard, Paul Calès, V. de Ledinghen, Véronique Loustaud-Ratti, M. Bourlière, Isabelle Rosa, Fabrice Carrat, Véronique Grando-Lemaire, Fabien Zoulim, V. Di Martino, C. Dufour, Ghassan Riachi, Pierre-Henri Bernard, Jean-Pierre Bronowicki, Isabelle Portal, Lawrence Serfaty, T. Fontanges, Patrick Marcellin, J.-J. Raabe, Dominique Guyader, Xavier Causse, Jean-Pierre Zarski, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de recherche sur les Ions, les MAtériaux et la Photonique (CIMAP - UMR 6252), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), 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), 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), Service d'Hépato-gastroentérologie, Assistance Publique - Hôpitaux de Marseille (APHM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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 des maladies du foie [CHU Rennes], Centre Hospitalier Universitaire [Rennes], 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 ), CHU Pitié-Salpêtrière [AP-HP], SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA), Centre Hospitalier Universitaire de Nice (CHU Nice), 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), ESIM - Déterminants Sociaux de la Santé et du Recours aux Soins (DS3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche en Cancérologie de Montpellier ( IRCM - U1194 Inserm - UM ), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Centre de recherche sur les Ions, les MAtériaux et la Photonique ( CIMAP - UMR 6252 ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Supérieure d'Ingénieurs de Caen ( ENSICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ), 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Assistance Publique - Hôpitaux de Marseille ( APHM ), Service d'hépatologie [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], 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 ), 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, 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 Pitié-Salpêtrière [APHP], 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 ), CIRAD, UPR AGIRs, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Epidémiologie, Systèmes dínformation et modélisation ( ESIM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Unité de Santé Publique, Assistance publique - Hôpitaux de Paris - AP-HP (FRANCE)-CHU Saint-Antoine [APHP], Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), 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), Université Paris-Sud - Paris 11 (UP11)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Centre Hospitalier Universitaire [Rennes], 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 ), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Service d'hépatologie [CHU Saint-Antoine], Centre Hospitalier Universitaire [Rennes]-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou
Subjects: 0303 health sciences, Pediatrics, medicine.medical_specialty, Hepatology, [ SDV ] Life Sciences [q-bio], business.industry, [SDV]Life Sciences [q-bio], Treatment experienced, 3. Good health, Telaprevir, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, Boceprevir, Cohort, medicine, 030211 gastroenterology & hepatology, business, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, medicine.drug
Abstract: International audience; no abstract
Published: 2015

25. Efficacy and safety of aciclovir mucoadhesive buccal tablet in immunocompetent patients with labial herpes (LIP Trial): a double-blind, placebo-controlled, self-initiated trial

Author: Thomas, Bieber, Olivier, Chosidow, Neil, Bodsworth, Stephen, Tyring, Jana, Hercogova, Mark, Bloch, Matthew, Davis, Michael, Lewis, David, Boutolleau, Pierre, Attali, and S K, Tyring
Subjects: Adult, Aged, 80 and over, Male, Adolescent, Acyclovir, Adhesiveness, Administration, Buccal, Middle Aged, Antiviral Agents, Young Adult, Drug Delivery Systems, Treatment Outcome, Double-Blind Method, Recurrence, Chronic Disease, Humans, Female, Herpes Labialis, Aged, Follow-Up Studies, Tablets
Abstract: Single-day, high-dose systemic antiviral drugs are effective in the treatment of labial herpes (herpes labialis [HL]). Aciclovir Lauriad® mucoadhesive buccal tablet (ABT) is an innovative drug delivery system providing high and prolonged exposure to aciclovir in the oral cavity, supporting its evaluation as a single low dose in HL.In this multicenter double-blind placebo-controlled patient-initiated trial, 775 patients with recurrent HL were randomly assigned to either a single application of ABT 50 mg or a matching placebo as soon as prodromal symptoms occurred. The primary endpoint was the time to healing (TTH) of primary vesicular lesion (modified intention-to-treat population). Other endpoints included incidence of blocked episodes, duration of herpes episodes, and incidence and time to next recurrence evaluated during a 9-month follow-up period (intention-to-treat population).With ABT 50 mg, median TTH of primary vesicular lesion was reduced (7 days vs 7.3 days, P=.015), the incidence of blocked herpes episodes was increased by 24.2% (34.9% vs 28.1%; P=.042), and the median duration of herpes episodes was reduced (5.6 days vs 6.4 days, P=.003). During the 9-month follow-up period, recurrence of herpes lesions was less frequent (64.2% vs 73.6%; P=.027) and delayed (205 days vs 165 days, P=.041) in the ABT 50 mg. Both treatments were safe.A single application of ABT improves all endpoints of HL and might modify its clinical course in decreasing the incidence and delaying the onset of the next recurrence.
Published: 2014

26. 0436: Diagnostic value of serial ultrasensible troponin I measurements for acute coronary syndrome identification in cardiac intensive care unit

Author: Hélène Kremer, Patrick Ohlmann, Ozlem Hopp, Hafida Samet, Pierre Attali, Sébastien Harscoat, Laurence Jesel, Nathan Messas, Morel Olivier, Thomas Lavaux, Pascal Bilbault, Sébastien Hess, and Ulun Crimizade
Subjects: Acute coronary syndrome, medicine.medical_specialty, biology, business.industry, medicine.disease, Chest pain, musculoskeletal system, Troponin, Pericarditis, Internal medicine, Heart failure, Troponin I, medicine, Coronary care unit, biology.protein, Cardiology, cardiovascular system, Myocardial infarction, medicine.symptom, business, Cardiology and Cardiovascular Medicine
Abstract: Introduction ACS diagnosis relies on the detection of an increase or a decrease in troponin levels (delta-TnI) that might be estimated as absolute (delta-TnI-abs) or relative value (delta-TnI-rel). The discriminative cut-off value of delta-TnI to identify ACS in patients admitted in ICU is a matter of debate. Methods We aimed to determine in a monocentric registry the cut-off value of delta-TnI to identify ACS among patients admitted in ICU with a suspicion of acute myocardial ischemia. All the patients had 2 measurements of ultrasensible cTnI (ADVIA Centaur Siemens®; 99th percentile: 0,04 μg/L). Patients were classified in 4 groups: 1) ACS (NSTEMI, UA), 2) Cardiac non coronary diseases (heart failure, PE, arrhythmia, pericarditis, myocarditis, syncope, Tako-Tsubo), 3) Non cardiac diseases (pneumonia, stroke, epilepsy, neoplasm), 4) Chest pain of unknown origin (musculo-skelettal pain…) Results 275 patients were included. Medians of delta-TnI-abs were 0.12 [0 ; 1.01] ; 0.01 [0 ; 0.03] ; 0 [-0.01 ; 0] et 0 [0 ; 0] μg/L in groups 1 to 4 respectively. Medians of delta-TnI-rel) were 104 [0 ; 680] ; 2 [0 ; 62] ; 0 [-6 ; 0] et 0 [0 ; 0] % in groups 1 to 4 respectively. The delta-TnI-abs was significantly different between groups 1 and 2 (p=0.026). ROC curve analysis showed that optimal threshold of delta-TnI-abs was 0.02 μg/L (sensitivity 67%, specificity 76%) to distinguish group 1 from groups 2, 3 and 4. The threshold was 0.04 μg/L (sensitivity 61%, specificity 80%) to distinguish group 1 from group 2. The use of delta-TnI-rel yielded similar results and the only confounder was age. Conclusion This study suggests that the cut-off of delta-TnI to identify ACS in ICU patients should be higher to be discriminative of cardiac non coronary diseases. The identification of type 1 and type 2 myocardial infarction is a major challenge and needs further research.
Published: 2014
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27. Comparison of the efficacy, safety, and onset of action of mizolastine, cetirizine, and placebo in the management of seasonal allergic rhinoconjunctivitis

Author: Jacques Daele, Alfred Sabbah, Paul Ben-Soussen, Alan Grierson Wade, and Pierre Attali
Subjects: Pulmonary and Respiratory Medicine, Allergy, medicine.medical_specialty, business.industry, Immunology, medicine.disease, Placebo, Gastroenterology, Cetirizine, law.invention, Clinical trial, Randomized controlled trial, law, Internal medicine, medicine, Immunology and Allergy, Onset of action, Adverse effect, business, medicine.drug, Mizolastine
Abstract: Background Mizolastine is a potent and selective H 1 -receptor antagonist with additional anti-allergic properties. Objective The aim of this European multicenter, randomized, double-blind study was to compare the efficacy of mizolastine 10 mg (n = 122), cetirizine 10 mg (n = 125), and placebo (n = 128) once daily for 28 days in patients with seasonal allergic rhinoconjunctivitis (SAR), with focus on the onset of action. Methods Symptoms were evaluated by the investigator using a total symptom score (TS) and by the patient (first week). Responders (R) were patients with a TS decrease of at least 50%. Safety was assessed according to the spontaneous reporting of adverse events. Results Both mizolastine and cetirizine were effective in relieving the symptoms of SAR. After 7 days of treatment, the improvement in TS and responder's rate were significantly ( P P = .027) and third ( P = .050) day. Both mizolastine and cetirizine were well tolerated. Conclusion Mizolastine 10 mg once daily is at least as effective as cetirizine in relieving symptoms of SAR, onset of action is rapid with clinical effect evident within 2 hours.
Published: 1999

28. P1334 : A multicentre, randomised, open-label study comparing the efficacy and safety of two doses of Doxorubicin TransdrugTM to best standard of care in patients with advanced Hepatocellular Carcinoma (HCC) after sorafenib. The relive study

Author: Ivan Borbath, Henning Wege, G.-P. Pageaux, Z. Horváth, G. Sánchez Antolín, Philippe Merle, François Habersetzer, Jean-Pierre Bronowicki, A. Maieron, G. Luca Frassineti, René Gerolami, Pierre Attali, Gilles Pelletier, J.-F. Blanc, Yann Touchefeu, B. Vasseur, N. Gabrail, and V. Breder
Subjects: Oncology, Sorafenib, medicine.medical_specialty, Standard of care, Hepatology, business.industry, medicine.disease, Open label study, Hepatocellular carcinoma, Internal medicine, medicine, Doxorubicin, In patient, business, medicine.drug
Published: 2015

29. Triple therapy in treatment-experienced patients with HCV-cirrhosis in a multicentre cohort of the French Early Access Programme (ANRS CO20-CUPIC) – NCT01514890

Author: Stanislas Pol, Thierry Poynard, Isabelle Rosa, Armand Abergel, Valérie Canva, Lawrence Serfaty, Véronique Loustaud-Ratti, Jean-Pierre Zarski, Cyrille Feray, Xavier Causse, Patrick Hillon, J.-J. Raabe, Fabien Zoulim, Christophe Hézode, Pierre Attali, Dominique Guyader, Hélène Fontaine, Pierre-Henri Bernard, Patrice Cacoub, Laurent Alric, Didier Samuel, Dominique Larrey, Céline Dorival, Albert Tran, Ventzislava Petrov-Sanchez, Marc Bourlière, Ghassan Riachi, Jean-Michel Pawlotsky, Patrick Marcellin, Fabrice Carrat, Véronique Grando-Lemaire, Sophie Metivier, Damien Lucidarme, Vincent Di Martino, Victor de Lédinghen, Thong Dao, Jean-Pierre Bronowicki, Yoann Barthe, 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 Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ESIM - Déterminants Sociaux de la Santé et du Recours aux Soins (DS3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche en biothérapie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), 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'Hépato-gastroentérologie [CHU Lille], 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), Département d'hépatologie et de gastroentérologie [CHU Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pathologies biliaires, fibrose et cancer du foie, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Service d'hépato-gastro-entérologie, Assistance Publique - Hôpitaux de Marseille (APHM), 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-gastro-entérologie [CHR Metz-Thionville], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), 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, 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 biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-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), Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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), CHU Saint-Antoine [AP-HP], Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Image Science for Interventional Techniques (ISIT), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Centre National de la Recherche Scientifique (CNRS), Service d’Hépato-Gastro-Entérologie [Orléans], Centre Hospitalier Régional d'Orléans (CHRO), Service d'Hépatologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), 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 ), Groupe Hospitalier de l'Institut Catholique Lillois, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service Hépato-gastroentérologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), 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), 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), CHI Créteil, Service d'Hépato-gastro-entérologie [APHP Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Recherches fondamentales, cliniques et thérapeutiques sur les hépatites virales, ANRS France Recherche Nord & sud Sida-hiv hépatites, Service de bactériologie, virologie, hygiène [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], 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, Hôpital Charles Nicolle [Rouen]-CHU Rouen, CHU Toulouse [Toulouse], 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), 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 de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Service de santé publique [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 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), Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges, Service d'Hépato-Gastroentérologie [Purpan-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), Service d'hépatologie [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)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Jean Verdier [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)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Pathologies biliaires, fibrose et cancer du foie (Inserm UMR_S 938), CHU Saint-Antoine [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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'Hépato-Gastroentérologie [Rouen], Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'Hépato-Gastroentérologie [CHRU Clermont-Ferrand], Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont Université-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Centre Hospitalier Régional d'Orléans (CHR), Service d'Hépatologie, Hôpital Jean Minjoz, Centre Hospitalier Universitaire de Besançon, Université de Franche Comté, Hôpital Jean Minjoz, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], and Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Liver Cirrhosis, Male, Cirrhosis, Blood transfusion, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Chronic hepatitis C, Gastroenterology, Telaprevir, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Pegylated interferon, Medicine, Prospective Studies, Aged, 80 and over, Boceprevir, Middle Aged, Viral Load, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Cohort, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, France, Safety, Oligopeptides, medicine.drug, Adult, medicine.medical_specialty, Serine Proteinase Inhibitors, Proline, Antiviral Agents, 03 medical and health sciences, Internal medicine, Ribavirin, Humans, Adverse effect, Aged, Hepatology, business.industry, Interferon-alpha, Hepatitis C, Chronic, medicine.disease, Surgery, Treatment, chemistry, business
Abstract: International audience; Background & AimsIn phase III trials, the safety profile of triple therapy (pegylated interferon/ribavirin with boceprevir or telaprevir) seems to be similar in HCV treatment-experienced cirrhotic and non-cirrhotic patients, but few cirrhotics were included. We report the week 16 safety and efficacy analysis in a cohort of compensated cirrhotics treated in the French Early Access Programme.Methods674 genotype 1 patients, prospectively included, received 48 weeks of triple therapy. The analysis is restricted to 497 patients reaching week 16.ResultsA high incidence of serious adverse events (40.0%), and of death and severe complications (severe infection or hepatic decompensation) (6.4%), and a difficult management of anaemia (erythropoietin and transfusion use in 50.7% and 12.1%) were observed. Independent predictors of anaemia
Published: 2013

30. Gene electrotransfer of plasmid antiangiogenic metargidin peptide (AMEP) in disseminated melanoma: safety and efficacy results of a phase I first-in-man study

Author: Bérangère Vasseur, Iben Spanggaard, Lluis M. Mir, Pierre Attali, Elisabeth Dam, Gregor Sersa, Julie Gehl, Caroline Robert, Maja Cemazar, Marko Snoj, Céline Bouquet, and Andrea Cavalcanti
Subjects: Male, Skin Neoplasms, Gene electrotransfer, Angiogenesis Inhibitors, Pharmacology, Transfection, Plasmid, Pharmacokinetics, Medicine, Humans, RNA, Messenger, Melanoma, Genetics (clinical), Aged, First-in-man study, business.industry, Electroporation, Membrane Proteins, Genetic Therapy, Middle Aged, medicine.disease, Reverse transcriptase, Protein Structure, Tertiary, ADAM Proteins, Treatment Outcome, Tolerability, Female, business, Plasmids
Abstract: Antiangiogenic metargidin peptide (AMEP) is a novel anticancer agent exerting antiproliferative and antiangiogenic effects by binding to αvβ3 and α5β1 integrins. Electrotransfer designates the use of electric pulses (electroporation) to transfer plasmid DNA into tissues. This first-in-man phase I study investigated safety and tolerability of intratumoral plasmid AMEP electrotransfer into cutaneous metastatic melanoma. Secondary objectives were efficacy and pharmacokinetics. Five patients with disseminated melanoma without further treatment options were treated at two dose levels (1 and 2 mg DNA). In each patient, two cutaneous lesions were identified (one treated and one control). At day 1 and day 8, plasmid AMEP was injected intratumorally followed by electrotransfer. Patients were monitored weekly until day 29, and at day 64. Local efficacy was assessed at day 29 by direct measurement, and posttreatment biopsies for AMEP mRNA levels were evaluated by reverse transcriptase quantitative polymerase chain reaction. Plasmid copy number in blood and urine was determined by quantitative polymerase chain reaction. Minimal systemic toxicity was observed, including transient fever and transitory increase in C-reactive protein. No related serious adverse events occurred. Plasmid AMEP was detected in plasma but not in urine. AMEP mRNA was found in three of five treated lesions and none of the control lesions. At day 29, all five treated lesions were stable in diameter, whereas four of five control lesions increased more than 20%. No response occurred in distant lesions. This first-in-man study on electrotransfer of plasmid AMEP into cutaneous melanoma shows that the procedure and drug are safe and that local transfection was obtained.
Published: 2013

31. Efficacy and Safety of Mizolastine in Seasonal Allergic Rhinitis

Author: Francisque Leynadier, Jean Bousquet, Margarita Murrieta, and Pierre Attali
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Allergy, business.industry, medicine.medical_treatment, Immunology, Parallel study, Histamine H1 receptor, Placebo, medicine.disease, Surgery, Internal medicine, Immunopathology, medicine, Immunology and Allergy, Antihistamine, Adverse effect, business, Mizolastine, medicine.drug
Abstract: Background Mizolastine is a new, nonsedating antihistamine under clinical investigation for treatment of allergic rhinitis and urticaria. Objective The purpose of this study was to determine the optimally active dose of once-daily mizolastine in seasonal allergic rhinitis. Methods This multicenter, double-blind, parallel study involved 494 patients randomly allocated to mizolastine (5, 10, or 15 mg) or placebo for 2 weeks. Results Physicians' assessments indicated the superiority of 10 and 15 mg mizolastine to placebo in reducing total symptom scores (P = .002), nasal scores ( P = .004), and ocular scores (P = .007) at day 7. Patients' diaries showed a significant change from baseline in daily symptom scores as early as day 2 (P = .01) in 10- and 15-mg mizolastine groups in comparison to placebo, but this was not maintained throughout the study. No additional benefits were demonstrated during the second week of treatment in terms of efficacy. Adverse events were slightly more frequent in the 15-mg mizolastine group. Conclusion This study confirms mizolastine is an effective and well tolerated antihistamine in the treatment of seasonal allergic rhinitis; 10 mg is the optimal dose.
Published: 1996

32. A Clinically Relevant Case Study: the Development of Livatag® for the Treatment of Advanced Hepatocellular Carcinoma

Author: Philippe Merle, Emilienne Soma, and Pierre Attali
Subjects: Oncology, medicine.medical_specialty, business.industry, Internal medicine, Hepatocellular carcinoma, medicine, Developing country, Cancer, High incidence, medicine.disease, business, Sex ratio
Abstract: Hepatocellular carcinoma (HCC) is the fifth most common cancer in men (523 000 cases) and the seventh in women (226 000 cases). Most of the burden is in developing countries, where almost 85% of the cases occur, and particularly in men: the overall sex ratio male/female is around 4. High incidence r...
Published: 2012

33. P1111 ANRS HC15 NRFI: LONG-TERM MAINTENANCE THERAPY WITH A COMBINATION OF RIBAVIRIN AND PEGYLATED INTERFERON IN CHRONIC HEPATITIS C. RESULTS OF A MULTICENTER RANDOMIZED CONTROLLED TRIAL

Author: Michel Doffoel, Jean Henrion, Paul Calès, Jérôme Gournay, Louis d’Alteroche, L Lasser, Alain Renault, Michel Beaugrand, C. Trepo, T. Asselah, Bruno Turlin, M. Bourlière, Claire Wartelle, M Schnee, Ghassan Riachi, Jean Delwaide, P. Bedossa, Pierre Attali, M. Adler, Eric Bellissant, Didier Samuel, Jean-Pierre Vinel, Albert Tran, Armando Abergel, Dominique Guyader, Jean-Pierre Bronowicki, and Patrick Hillon
Subjects: medicine.medical_specialty, Hepatology, business.industry, Ribavirin, Long term maintenance, Gastroenterology, law.invention, chemistry.chemical_compound, Randomized controlled trial, chemistry, Chronic hepatitis, Pegylated interferon, law, Internal medicine, medicine, business, medicine.drug
Published: 2014

34. Halothane-anesthetized rabbit: a new experimental model to test the effects of besipirdine and duloxetine on lower urinary tract function

Author: Francisco C. Pérez-Martínez, Julio Virseda, Moez Rekik, Remigio Vela-Navarrete, Stefano Palea, Ana V. Ocaña, Pierre Attali, Philippe Lluel, Hugues Bienayme, and Jacques Ferte
Subjects: medicine.medical_specialty, Indoles, Pyridines, Urology, Metabolite, Urinary system, Thiophenes, Atomoxetine Hydrochloride, Duloxetine Hydrochloride, chemistry.chemical_compound, Norepinephrine, In vivo, medicine, Prazosin, Potency, Duloxetine, Animals, Humans, Anesthesia, Urinary Tract, Anesthetics, Retrospective Studies, Dose-Response Relationship, Drug, Propylamines, business.industry, Electromyography, Muscle, Smooth, Disease Models, Animal, Urodynamics, Urethra, medicine.anatomical_structure, chemistry, Urinary Tract Infections, Female, Rabbits, Halothane, business, medicine.drug
Abstract: Introduction: The effects of besipirdine and its main metabolite, HP-748, as well as duloxetine and tomoxetine in the lower urinary tract (LUT) were studied using in vitro and in vivo techniques. Materials and Methods: For in vivo studies, besipirdine or duloxetine effects on cystometric parameters and striated sphincter electromyographic (SS-EMG) activity were investigated. On the isolated urethra, norepinephrine (NE) concentration-response curves (CRC) were performed in the presence of besipirdine, duloxetine or tomoxetine. Moreover, CRC to HP-748 were constructed in the absence or presence of prazosin. Potency (pEC50) and maximal responses (Emax) were determined. Results: Besipirdine at 1, 3 and 5 mg/kg intravenously (i.v.) induced a significant increase in SS-EMG activity (250, 273 and 241%, respectively), bladder capacity (172, 197, and 235%, respectively), intercontraction interval (ICI; 208, 242, and 400%, respectively), and residual volume (181, 191, and 236%, respectively). Duloxetine at 2 mg/kg i.v. increased significantly SS-EMG activity (219%), micturition volume (222%), and ICI (205%). In the isolated urethra, besipirdine, tomoxetine and duloxetine significantly displaced to the left the NE CRC. In addition, HP-748 induced contraction of the isolated urethra with a pEC50 of 5.89 and an Emax of 37%. Conclusions: These data support the potential of besipirdine as a new drug for LUT dysfunctions such as stress and mixed urinary incontinence.
Published: 2010

35. Asymptomatic bacterascites: Is it spontaneous bacterial peritonitis?

Author: Hervé Hagège, Pierre Attali, Jean-Pierre Etienne, Olivier Ink, Catherine Buffet, Gilles Pelletier, and Gilles Lesur
Subjects: Adult, Male, medicine.medical_specialty, Cirrhosis, Peritonitis, Gastroenterology, Asymptomatic, Liver disease, Spontaneous bacterial peritonitis, Internal medicine, Ascites, Humans, Medicine, Aged, Aged, 80 and over, Brain Diseases, Bacteria, Hepatology, business.industry, Mortality rate, Bacterial Infections, Middle Aged, medicine.disease, Nutrition Disorders, Surgery, medicine.symptom, Gastrointestinal Hemorrhage, business, Complication
Abstract: Asymptomatic bacterascites is defined as the presence of bacteria in ascitic fluid without clinical features of peritonitis or increased ascitic fluid polymorphonuclear cells. Asymptomatic bacterascites is a controversial entity, and little information is available regarding its spontaneous evolution. Clinical features, bacteriological data and outcome in 22 cirrhotic patients with asymptomatic bacterascites are reported and are compared with those of a group of 36 cirrhotic patients with spontaneous bacterial peritonitis. Eleven patients had gram-negative bacteria and 11 had one gram-positive bacteria. Only in three patients (13.6%) did peritonitis develop. Twelve patients received no antibiotic therapy, and in none did peritonitis develop. At 1 month, 27% of patients with asymptomatic bacterascites had died. Patients with asymptomatic bacterascites had less-severe liver disease; they more frequently had gram-positive bacteria in ascitic fluid and had a lower 1-mo mortality rate than did patients with spontaneous bacterial peritonitis. We conclude that asymptomatic bacterascites is usually the transient residence of bacteria in ascitic fluid. Peritonitis rarely develops in patients with asymptomatic bacterascites and, in most of them, antibiotic therapy is not required.
Published: 1991

36. Culture-negative neutrocytic ascites: a less severe variant of spontaneous bacterial peritonitis

Author: Jean-Pierre Etienne, D. Salmon, Catherine Buffet, Gilles Pelletier, S. Hannoun, Pierre Attali, and Olivier Ink
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Neutrophils, Peritonitis, Gastroenterology, chemistry.chemical_compound, Spontaneous bacterial peritonitis, Internal medicine, Ascites, medicine, Humans, Cells, Cultured, Aged, Retrospective Studies, Creatinine, Hepatology, business.industry, Genetic Variation, Retrospective cohort study, Bacterial Infections, Middle Aged, medicine.disease, Surgery, Liver, chemistry, Relative risk, Female, Culture negative, medicine.symptom, business
Abstract: The clinical signs and symptoms, the biological data and the prognosis of 38 cirrhotic patients with culture-positive spontaneous bacterial peritonitis and 15 cirrhotic patients with culture-negative neutrocytic ascites were compared. The diagnosis of culture-negative neutrocytic ascites was based on the following criteria: an ascitic fluid polymorphonuclear count greater than 250/mm3, a negative ascitic fluid culture and the absence of previous antibiotic therapy and intraabdominal source of infection. All patients were treated by antibiotic therapy. There were no differences in clinical signs and symptoms and Pugh grading between the two groups of patients. Serum creatinine and prevalence of positive-blood culture were higher in spontaneous bacterial peritonitis. Patients with culture-positive spontaneous bacterial peritonitis had a higher ascitic fluid polymorphonuclear count and a lower ascitic fluid pH. Mortality was higher in patients with culture-positive spontaneous bacterial peritonitis than in patients with culture-negative neutrocytic ascites (relative risk: 2.6, p less than 0.01): cumulative mortality was, respectively, 50% and 20% at 1 months, 61% and 33% at 6 months, 75% and 41% at 1 year. The higher mortality observed in patients with culture-positive spontaneous bacterial peritonitis persisted after hospitalization (relative risk: 3, p less than 0.03). Our results suggest that culture-negative neutrocytic ascites is a less severe variant of spontaneous bacterial peritonitis.
Published: 1990

37. Comparison of the efficacy and safety of miconazole 50-mg mucoadhesive buccal tablets with miconazole 500-mg gel in the treatment of oropharyngeal candidiasis: a prospective, randomized, single-blind, multicenter, comparative, phase III trial in patients treated with radiotherapy for head and neck cancer

Author: Andrzej Rosikon, Jamel Daoud, Brahim El Gueddari, Rene Gourmet, Pierre Attali, Philippe Ceruse, Christophe Allavena, René-Jean Bensadoun, Gilles Calais, and Laurent Bastit
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Antifungal Agents, Adolescent, Miconazole, Oropharyngeal Candidiasis, law.invention, Randomized controlled trial, law, Candidiasis, Oral, medicine, Clinical endpoint, Humans, Aged, Aged, 80 and over, Radiotherapy, business.industry, Head and neck cancer, Cancer, Buccal administration, Middle Aged, medicine.disease, Surgery, Clinical trial, Oncology, Head and Neck Neoplasms, Female, business, Gels, medicine.drug, Tablets
Abstract: Topical antifungal treatments are recommended but rarely used as first-line therapy for oropharyngeal candidiasis (OPC) in patients with cancer. Miconazole Lauriad 50-mg mucoadhesive buccal tablet (MBT) Loramyc reportedly delivered rapid and prolonged, effective concentrations of miconazole in the mouth. The objective of the current study was to compare MBT with miconazole 500-mg oral gel (MOG) in patients with head and neck cancer.Two hundred eighty-two patients with head and neck cancer received a 14-day treatment of either single-dose MBT or MOG administered in 4 divided doses. The primary endpoint was clinical success at Day 14, and secondary endpoints included clinical success at Day 7, clinical cure, improvement in clinical symptoms, mycologic cure, recurrence rate, and safety.The success rate was statistically not inferior (P.0001) in the MBT population to the rate observed in the MOG group (56% vs 49%, respectively; P.0001). After adjustment for the extent of lesions and salivary secretions, a trend toward superiority was observed in favor of MBT (P = .13), particularly among patients with multiple lesions (P = .013). Results for secondary endpoints were comparable to those observed for the primary endpoint. Compliance with MBT was excellent, and80% of patients completed treatment. Both treatments were safe.The success rate of MBT Loramyc was significantly not inferior to that of MOG in the treatment of cancer patients with OPC; and, after adjusting for prognostic variables, it was more effective than MOG. MBT was well tolerated and, thus, may be recommended as first-line treatment in cancer patients who have OPC as an alternative to systemic antifungal agents. Society.
Published: 2007

38. Mucoadhesive clonidine (Clonidine Lauriad) in the prevention of severe radiomucositis in head and neck cancer patients: A phase II randomized trial

Author: Jorge Contreras-Martinez, Esat Mahmut Ozsahin, Philippe Ceruse, Gabor Pajkos, Xavier Zasadny, Jordi Giralt, René-Jean Bensadoun, Pierre Attali, Yungan Tao, Michael Henke, Bérangère Vasseur, Rajesh V. Lalla, Fernando Arias de la Vega, and Rolf-Dieter Kortmann
Subjects: Cancer Research, medicine.medical_specialty, business.industry, Head and neck cancer, medicine.disease, law.invention, Clonidine, Surgery, Oncology, Randomized controlled trial, law, Anesthesia, Mucositis, Medicine, Clonidine Lauriad, business, Severe complication, Chemoradiotherapy, medicine.drug
Abstract: 6058 Background: Oral mucositis (OM) is the most frequent and severe complication of chemoradiotherapy (CRT) in head and neck cancer patients. There is currently no effective mechanistically-target...
Published: 2015

39. P1262 : An accurate score for the prediction of sustained viral response under protease inhibitor-based triple therapy in cirrhotic patients: The cupic algorithm – the ANRS CO20 CUPIC study

Author: Laurent Alric, Christophe Hézode, Pierre Attali, Patrice Cacoub, Paul Calès, V. de Ledinghen, Thierry Poynard, M. Bourlière, Dominique Larrey, Hélène Fontaine, C. Dufour, Pascal Veillon, Jean-Pierre Bronowicki, S. Allam, Valérie Moal, J. Vergniol, Jean-Pierre Zarski, Jérôme Boursier, Valérie Canva, Fabrice Carrat, and Fabien Zoulim
Subjects: Hepatology, business.industry, Sustained viral response, Medicine, Protease inhibitor (pharmacology), business, Virology
Published: 2015

40. Hereditary persistence of alpha-fetoprotein is due to both proximal and distal hepatocyte nuclear factor-1 site mutations

Author: Youssef, Alj, Maria, Georgiakaki, Jean-François, Savouret, Frédéric, Mal, Pierre, Attali, Gilles, Pelletier, Catherine, Fourré, Edwin, Milgrom, Catherine, Buffet, Anne, Guiochon-Mantel, and Gabriel, Perlemuter
Subjects: Male, Binding Sites, Base Sequence, Molecular Sequence Data, Nuclear Proteins, Middle Aged, Pedigree, DNA-Binding Proteins, Hepatocyte Nuclear Factor 1, Mutation, Humans, Hepatocyte Nuclear Factor 1-alpha, alpha-Fetoproteins, Promoter Regions, Genetic, Hepatocyte Nuclear Factor 1-beta, Transcription Factors
Abstract: The molecular mechanism of hereditary persistence of alpha-fetoprotein (HPAFP) has been previously described in a large Scottish family, consisting of a -119GA substitution in the distal hepatocyte nuclear factor 1 (HNF-1) binding site of the alpha-fetoprotein (AFP) gene promoter. We report here the molecular mechanisms of HPAFP in 2 new unrelated families.Family 1 was of Bengali origin, and family 2 was Italian. Four of 5 subjects (family 1) and 3 of 9 (family 2) showed HPAFP. The AFP gene promoter was studied in all available family members.All subjects with high AFP levels had mutated promoter sequences. Family 1 showed the reported -119GA substitution. Family 2 showed -55CA and -65CT substitutions in the proximal putative HNF-1 binding region of the promoter. The -55CA mutation increased the similarity of the proximal HNF-1 binding region to a consensus binding region. Gel shift assays confirmed its increased affinity toward HNF-1, and transfection experiments revealed an increased level of gene transcription. The -65CT substitution theoretically created a CCAAT box. However, gel shift and transfection experiments failed to show any biological effect of this substitution that is associated with the -55CA mutation.Two different mutations localized in either HNF-1 binding sites of the AFP gene promoter may result in HPAFP. This highlights the importance of HNF-1 in AFP gene expression. Unexplained persistent AFP should lead to family study and/or AFP gene promoter sequencing to avoid inappropriate explorations and treatment decisions.
Published: 2003

41. Effectiveness of telaprevir or boceprevir in treatment-experienced patients with HCV genotype 1 infection and cirrhosis. : Triple therapy in HCV genotype 1 cirrhotics

Author: Thierry Poynard, Veronique Loustaud Ratti, Dominique Larrey, Isabelle Portal, Patrick Marcellin, Albert Tran, Vincent Di Martino, Patrick Hillon, Jean-Pierre Bronowicki, Isabelle Rosa, Damien Lucidarme, Marc Bourlière, Ghassan Riachi, Christophe Hézode, Pierre Attali, Yoann Barthe, Patrice Cacoub, Olivier Chazouillères, Pierre Bernard, Veronique Grando–Lemaire, Jérôme Gournay, Sophie Metivier, Thong Dao, Stanislas Pol, Jean-Pierre Zarski, Valérie Canva, Victor de Lédinghen, Ventzislava Petrov–Sanchez, Jean-Michel Pawlotsky, Armand Abergel, Laurent Alric, Didier Samuel, Fabrice Carrat, Hélène Fontaine, Jean Jacques Raabe, Céline Dorival, Fabien Zoulim, Xavier Causse, Dominique Guyader, T. Fontanges, 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], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service d'hépatologie médicale [CHU Cochin], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Epidémiologie, Systèmes d'Information, Modélisation, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP], 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 ), Services d'hépatologie, Hospices Civils de Lyon ( HCL ), Service d'hépatologie, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -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, Hôpital Huriez-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale ( INSERM ), 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 ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Pathogénèse et traitement de l'hépatite fulminante et du cancer du foie, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance Publique - Hôpitaux de Marseille ( APHM ), Service de médecine interne et maladies digestives, 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-gastro-entérologie [CHR Metz-Thionville], Centre hospitalier régional Metz-Thionville ( CHR Metz-Thionville ), 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'hépato-gastroentérologie, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Centre de recherche biomédicale Bichat-Beaujon ( CRB3 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), 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-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques ( RESINFIT ), CHU Limoges-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST ), Université de Limoges ( UNILIM ) -Université de Limoges ( UNILIM ), 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 Etaing, Image Science for Interventional Techniques ( ISIT ), Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Clermont Université-Centre National de la Recherche Scientifique ( CNRS ), Service des maladies du foie, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [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 de Gastro-entérologie - Hépatologie [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Département digestif, 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 ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Hépato-gastro-entérologie et oncologie digestive, Centre Hospitalier Régional d'Orléans ( CHR ), Service d'Hépato-Gastro-Enterologie et Nutrition [Caen], Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -CHU Caen, Mobilités : Attention, Orientation et Chronobiologie ( COMETE ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Groupe Hospitalier de l'Institut Catholique Lillois, Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Service de médecine interne [CHU Pitié-Salpétrière], Immunologie - Immunopathologie - Immunothérapeutique ( 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 ), Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Hôpital Hôtel-Dieu [Paris], Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Jean Verdier, Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, CH Pierre Oudot Bourgoin-Jallieu, CHI Créteil, Recherches fondamentales, cliniques et thérapeutiques sur les hépatites virales, ANRS, Centre National de Référence Virus des hépatites B, C et Delta, Pôle de Pharmacie - Santé Publique - Information médicale [Saint-Antoine], 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 ), This study was sponsored and funded by The National Agency for Research on AIDS and Viral Hepatitis (ANRS).The ANRS C020 CUPIC cohort study was conducted with the support and participation of the Association Française pour l'Etude du Foie (AFEF), and CUPIC STUDY GROUP
Subjects: Liver Cirrhosis, Male, Cirrhosis, Comorbidity, Hepacivirus, medicine.disease_cause, Gastroenterology, Polyethylene Glycols, Telaprevir, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Pegylated interferon, boceprevir, Prospective Studies, Treatment Failure, Aged, 80 and over, Middle Aged, Recombinant Proteins, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, Oligopeptides, medicine.drug, Adult, medicine.medical_specialty, Genotype, Proline, Hepatitis C virus, Antiviral Agents, 03 medical and health sciences, Boceprevir, Internal medicine, Ribavirin, medicine, chronic hepatitis C, Humans, telaprevir, Adverse effect, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Aged, Hepatology, business.industry, cirrhosis, Interferon-alpha, Odds ratio, Hepatitis C, Chronic, medicine.disease, chemistry, Multivariate Analysis, Immunology, business, Follow-Up Studies
Abstract: International audience; BACKGROUND & AIMS: We investigated the effectiveness of the protease inhibitors peginterferon and ribavirin in treatment-experienced patients with hepatitis C virus (HCV) genotype 1 infection and cirrhosis. METHODS: In the Compassionate Use of Protease Inhibitors in Viral C Cirrhosis study, 511 patients with HCV genotype 1 infection and compensated cirrhosis who did not respond to a prior course of peginterferon and ribavirin (44.3% relapsers or patients with viral breakthrough, 44.8% partial responders, and 8.0% null responders) were given either telaprevir (n = 299) or boceprevir (n = 212) for 48 weeks. We assessed percentages of patients with sustained viral responses 12 weeks after therapy and safety. This observational study did not allow for direct comparison of the 2 regimens. RESULTS: Among patients given telaprevir, 74.2% of relapsers, 40.0% of partial responders, and 19.4% of null responders achieved SVR12. Among those given boceprevir, 53.9% of relapsers, 38.3% of partial responders, and none of the null responders achieved SVR12. In multivariate analysis, factors associated with SVR12 included prior response to treatment response, no lead-in phase, HCV subtype 1b (vs 1a), and baseline platelet count greater than 100,000/mm(3). Severe adverse events occurred in 49.9% of cases, including liver decompensation, severe infections in 10.4%, and death in 2.2%. In multivariate analysis, baseline serum albumin level less than 35 g/L and baseline platelet counts of 100,000/mm(3) or less predicted severe side effects or death. CONCLUSIONS: Relatively high percentages of real-life, treatment-experienced patients with HCV genotype 1 infection and cirrhosis respond to the combination of peginterferon and ribavirin with telaprevir or boceprevir. However, side effects are frequent and often severe. Baseline levels of albumin and platelet counts can be used to guide treatment decisions. ClinicalTrials.gov number: NCT01514890.
Published: 2014

42. Effect of clonidine on proinflammatory cytokine levels in ex vivo human oral mucosa

Author: Vanessa Roulet, Boisnic Nicole, Lorraine Zakin, Veronique Trochon-Joseph, Caroline Lemarchand, and Pierre Attali
Subjects: endocrine system, Cancer Research, business.industry, biochemical phenomena, metabolism, and nutrition, Pharmacology, medicine.disease, Clonidine, Proinflammatory cytokine, Pathogenesis, medicine.anatomical_structure, Oncology, medicine, Mucositis, α2 adrenergic, Oral mucosa, business, Ex vivo, medicine.drug
Abstract: e20689 Background: A strategy for the attenuation of oral mucositis is inhibition of pro-inflammatory cytokines (PIC) which have been implicated in its pathogenesis. Clonidine, a α2 adrenergic agon...
Published: 2014

43. Effect of topical clonidine on the duration and severity of radiation-induced oral mucositis (OM) in a translational hamster model

Author: Stephen T. Sonis, Pierre Attali, Lorraine Zakin, Greg Lyng, Vanessa Roulet, Caroline Lemarchand, and Veronique Trochon-Joseph
Subjects: Cancer Research, Oncology, business.industry, Mucositis, Medicine, Hamster, Radiation induced, Adrenergic agonist, Pharmacology, business, medicine.disease, Clonidine, medicine.drug
Abstract: 10091 Background: There is currently no effective mechanistically-targeted intervention for radiation-induced OM. Clonidine, a a2 adrenergic agonist, has been shown to impact NF-kappaB with consequ...
Published: 2014

44. Aortic valve tumour trapped in the right coronary ostium

Author: Pierre Attali, Jean-Marie Mossard, and Philippe Billaud
Subjects: Coronary angiography, Aortic valve, Male, medicine.medical_specialty, Myocardial Infarction, Fibroma, Coronary Angiography, Heart Neoplasms, Internal medicine, Thoracoscopy, Medicine, Humans, Myocardial infarction, Ultrasonography, medicine.diagnostic_test, business.industry, Images in Cardiology, Inferior Myocardial Infarction, Middle Aged, medicine.disease, Surgery, Coronary ostium, medicine.anatomical_structure, Aortic Valve, Coronary care unit, Cardiology, Cardiology and Cardiovascular Medicine, business
Abstract: A 48 year old man with a history of rectocolitis was admitted to a coronary care unit because of an inferior myocardial infarction. Revascularisation was not performed because of the absence of pain at the time of admission and delay …
Published: 2000

45. Proof of Concept of Gene Therapy Using Plasmid Amep in Disseminated Melanoma: Safety and Efficacy Results of A Phase I First-In-Man Study

Author: Marko Snoj, Gregor Sersa, Lluis M. Mir, Pierre Attali, Andrea Cavalcanti, Céline Bouquet, Iben Spanggaard, B. Vasseur, Caroline Robert, and Julie Gehl
Subjects: Oncology, medicine.medical_specialty, First-in-man study, business.industry, Genetic enhancement, Melanoma, Hematology, medicine.disease, Tolerability, Pharmacokinetics, Internal medicine, Toxicity, Cutaneous melanoma, medicine, business, Adverse effect
Abstract: Background AMEP (for Antiangiogenic MEtargidin Peptide) is a novel anti-cancer agent with proven anti-proliferative and anti-angiogenic properties by binding of avb3 and a5b1 integrins. Electrotransfer designates the use of electric pulses (electroporation) to transfer plasmid DNA into tissues, and is an attractive alternative to viral gene therapy. This study investigated safety and tolerability of intratumoural plasmid AMEP electrotransfer into cutaneous metastatic melanoma. Secondary objectives were efficacy and pharmacokinetics. Patients and methods Five pts with disseminated melanoma without further treatment options (median age 62 y, AJCC IIIC/IV, ECOG status ≤2) were treated at two dose levels (1 and 2 mg DNA) in a phase I study. In each patient, two cutaneous lesions were identified (one treated, one control). Under local anaesthesia, at day 1 and day 8, plasmid AMEP was injected intratumourally followed by electrotransfer with needle electrodes. Pts were monitored weekly until day 29, and at day 64. At day 29 local efficacy was assessed by measuring both lesions and post-treatment biopsies were obtained for determination of AMEP mRNA levels by RT-QPCR. Pharmacokinetic evaluation of plasmid AMEP by QPCR was performed on plasma and urine. Results The 5 pts received the 2 planned injections. Minimal systemic toxicity was observed including transient fever (1 pt) and transitory increase in C-Reactive Protein (2 pts). Local toxicity after injection was reported as mild. No related serious adverse events were seen. AMEP mRNA was found in 3 of 5 treated lesions and none of control lesions. Plasmid AMEP was detected in plasma in 4 of 5 pts, but not in urine. At day 29, all 5 treated lesions were stable in diameter, whereas 4 of 5 control lesions increased over 20 %. Response was not observed in any distant lesions. Conclusion This first-in-man study on electrotransfer of plasmid AMEP into cutaneous melanoma tumours shows local efficacy, efficiency of the DNA transfer method as well as an excellent safety profile. Further studies using the intramuscular route will evaluate whether a systemic efficacy of plasmid AMEP could be obtained using this transfer method. Disclosure C. Bouquet: Employee and stockholder at BioAlliance Pharma, who sponsored the study B. Vasseur: Employee at BioAlliance Pharma, who sponsored the study P. Attali: Employee and stockholder at BioAlliance Pharma who sponsored the study All other authors have declared no conflicts of interest.
Published: 2012

46. Impaired Salivary Flow Does Not Impair Miconazole Buccal Tablet Efficacy

Author: René-Jean Bensadoun, Naomi Musaji, and Pierre Attali
Subjects: Otorhinolaryngology, business.industry, Medicine, Surgery, Oral Surgery, Pharmacology, business, General Dentistry, Miconazole Buccal Tablet
Published: 2011

47. Efficacy of Miconazole Buccal Tablet in Severe Oropharyngeal Candidiasis

Author: J.B. Epstein, Lauren L. Patton, Pierre Attali, and N. Musaji
Subjects: medicine.medical_specialty, Otorhinolaryngology, business.industry, medicine, Surgery, Oral Surgery, business, General Dentistry, Miconazole Buccal Tablet, Dermatology, Oropharyngeal Candidiasis
Published: 2011

48. Sulindac causes regression of rectal polyps in familial adenomatous polyposis

Author: Labayle D, Pierre Attali, Alex Pariente, Michel Trousset, Olivier Duhamel, Philippe Vielh, François Drouhin, Bories C, and Fischer D
Subjects: Adult, Male, medicine.medical_specialty, Proliferation index, medicine.medical_treatment, Rectum, Placebo, Gastroenterology, Familial adenomatous polyposis, Sulindac, Double-Blind Method, Internal medicine, Biopsy, medicine, Humans, Rectal Polyp, Colectomy, Hepatology, medicine.diagnostic_test, business.industry, Rectal Neoplasms, Remission Induction, medicine.disease, digestive system diseases, medicine.anatomical_structure, Adenomatous Polyposis Coli, Female, business, medicine.drug
Abstract: In familial adenomatous polyposis, sulindac-induced polyp regression has been reported by several authors. In this study, the goal was to confirm these results by a randomized, placebo-controlled, double-blind crossover study in 10 patients with rectal polyps that had been previously treated by colectomy and ileorectal anastomosis. Patients received sulindac, 300 mg/day, or placebo during two 4-month periods separated by a 1-month wash-out phase. One patient was not compliant and was excluded. With sulindac, the authors observed a complete (6 patients) or almost complete (3 patients) regression of the polyps. With placebo, the authors observed an increase (5 patients), no change (2 patients), and a relative decrease (2 patients) in the number of polyps. The difference between sulindac and placebo was statistically significant (P less than 0.01). In biopsy specimens of polyps and normal rectal mucosa of 6 patients, the authors conducted an immunohistochemical study of the cellular proliferation index using the Ki 67 monoclonal antibody (Ki 67 index), at the beginning and at the end of each treatment period. They were not able to show a sulindac-induced modification of the Ki 67 index. The authors conclude that sulindac is effective in inducing the regression of rectal polyps in familial adenomatous polyposis.
Published: 1991

49. Diagnosis of Spontaneous Bacterial Peritonitis in Cirrhotic Patients

Author: Olivier Ink, Gilles Pelletier, Jean-Pierre Etienne, Pierre Attali, and Catherine Buffet
Subjects: Liver Cirrhosis, Bacteriological Techniques, medicine.medical_specialty, business.industry, Gastroenterology, Bacterial Infections, General Medicine, Peritonitis, medicine.disease, Spontaneous bacterial peritonitis, Internal medicine, medicine, Humans, business
Published: 1987

50. pH of ascitic fluid: Diagnostic and prognostic value in cirrhotic and noncirrhotic patients

Author: Gilles Pelletier, K. Turner, Olivier Ink, Jean-Pierre Etienne, and Pierre Attali
Subjects: Adult, Liver Cirrhosis, Male, Pathology, medicine.medical_specialty, Time Factors, Adolescent, Polymorphonuclear cell, Peritonitis, Ph measurement, Gastroenterology, Spontaneous bacterial peritonitis, Internal medicine, Ascites, medicine, Ascitic Fluid, Humans, Prospective Studies, Prospective cohort study, Aged, Ascitic fluid, Hepatology, business.industry, Bacterial Infections, Hydrogen-Ion Concentration, Middle Aged, Prognosis, medicine.disease, Female, medicine.symptom, business
Abstract: The pH measurements of 185 samples of ascitic fluid in 169 cirrhotic and 16 noncirrhotic patients were analyzed to assess their diagnostic and prognostic value. The 169 cirrhotic patients were divided into four groups: sterile ascites (group 1), spontaneous bacterial peritonitis (group 2), probable spontaneous bacterial peritonitis (group 3), and bacterascites (group 4). Mean ascitic fluid pH values were lower (p less than 0.001) in patients of groups 2 (7.24 +/- 0.17) and 3 (7.34 +/- 0.11) than in patients of groups 1 (7.44 +/- 0.06) and 4 (7.45 +/- 0.08), but there was an important overlap between these groups. Mean arterial-ascitic fluid pH gradient values were higher (p less than 0.001) in patients of groups 2 (0.21 +/- 0.16) and 3 (0.10 +/- 0.13) than in patients of groups 1 (0.02 +/- 0.05) and 4 (0.02 +/- 0.05). This gradient had a better discriminant power than ascitic fluid pH alone. Sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy for the diagnosis of certain or probable spontaneous bacterial peritonitis were, respectively, 47%, 99%, 88%, 89%, and 89% for ascitic fluid pH values less than 7.32; 66%, 99%, 91%, 93%, and 92% for arterial-ascitic fluid pH gradient values greater than 0.10; and 97%, 96%, 86%, 99%, and 96% for polymorphonuclear cell count greater than 75/microliter. Ascitic fluid pH values appeared to have a high prognostic value, as 6 of 7 cirrhotic patients with ascitic fluid pH values less than 7.15 died rapidly. Low ascitic fluid pH values were found in patients with malignant and pancreatic ascites and tuberculous peritonitis but not in patients with cardiac ascites. We conclude that in cirrhotic patients with certain or probable spontaneous bacterial peritonitis (a) arterial-ascitic fluid pH gradient measurements had a slightly higher diagnostic value than ascitic fluid pH measurements but a slightly lower diagnostic value than polymorphonuclear cell count and (b) ascitic fluid pH measurements had a high prognostic value. In noncirrhotic patients, ascitic fluid pH and arterial-ascitic fluid pH gradient measurements had a poor diagnostic value.
Published: 1986

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