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1. T cell immuno-phenotyping : a source of predictive biomarkers for autoimmune hepatitis relapse

Author: Astrid Imbert, Pierre-Jean Gavlovsky, Jean-Paul Judor, Edouard Bardou-Jacquet, Laure Elkrief, Adrien Lannes, Christine Silvain, Mathieu Schnee, Florence Tanne, Caroline Chevalier, Fabienne Vavasseur, Marion Khaldi, Sophie Brouard, Jean-François Mosnier, Jérôme Gournay, Sophie Conchon, and Amédée Renand
Subjects: Peripheral helper T cells, CD38, BAFF, Biomarkers, Personalized medicine, Medicine, Science
Abstract: Abstract Relapse after immunosuppression (IS) treatment withdrawal is frequent in patients with Autoimmune Hepatitis (AIH), and non-invasive biomarkers predictive of this risk are lacking. We assessed the frequency of circulating T cell subsets as potential biomarkers of disease activity and predictor of the risk of relapse after IS withdrawal. Serum levels of the cytokine B-cell Activating Factor (BAFF) were also investigated. Blood samples from 58 patients with active AIH, 56 AIH patients in remission, and 31 patients with NASH were analyzed. The frequency of activated CD4+ T peripheral helper (TPH) cells (CD4+CD45RA-CXCR5-PD1+CD38+) and of activated CD8+ T cells (CD8+CD45RA-PD1+CD38+) were assessed by flow cytometry. BAFF levels were determined by ELISA. Activated TPH and CD8+ T cell frequencies were significantly increased in patients with active AIH compared to remission AIH or NASH (TPH: 0.88% of total CD3+ vs. 0.42% and 0.39% respectively, p 0.5% of total CD3+) and/or activated CD8+ T cells (> 0.18% total CD3+) had a higher risk of relapse (80% vs. 15% after 2 years, p = 0.0071). High BAFF serum concentration (> 213pg/ml) was also associated to a higher risk of relapse (57% vs. 11%, p = 0.0452). In conclusion, high frequency of activated TPH and of activated CD8+, as well as high levels of BAFF, before IS discontinuation, were significantly associated to a greater risk of relapse during the first two years. Thus, they represent promising biomarkers to provide personalized clinical follow-up for patients with AIH.
Published: 2024
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2. Ex vivo cytokine production in psoriatic disease: Towards specific signatures in cutaneous psoriasis and peripheral psoriatic arthritis

Author: Guillaume Larid, Adriana Delwail, Thomas Dalle, Philippe Vasseur, Christine Silvain, Jean-François Jégou, Franck Morel, Jean-Claude Lecron, and Elisabeth Gervais
Subjects: psoriasis, psoriatic arthritis (PsA), psoriatic disease, cytokine signature, ex vivo stimulation, Immunologic diseases. Allergy, RC581-607
Abstract: ObjectivesPsoriatic arthritis (PsA) and cutaneous psoriasis (PsO) are different phenotypes of psoriatic disease (PsD), whose underlying specific mechanisms remain incompletely understood. As cytokines are key elements to induce and tune up immune responses to drive inflammatory diseases, our objective was to assess whether clinical features, disease phenotype and PsA and PsO activity were associated with a particular ex vivo cytokine production profile.MethodsForty-eight patients (37 PsA and 11 PsO) and 11 healthy subjects (HS) were studied. Cytokine production by peripheral blood mononuclear cells (PBMC) that were either unstimulated, or stimulated with LPS or anti-CD3/CD28 antibodies, were analysed by multiplex assay in the culture supernatants.ResultsCytokine signature of PsD includes a high level of TNFα in supernatants of LPS-stimulated PBMC, higher levels of IL-6 and lower levels of IFN-γ and IL-17A after CD3-CD28 stimulation, as well as higher spontaneous IL-1RA and TNFα production compared to HS. High body mass index (BMI) was associated with lower levels of IL-1β, and metabolic syndrome with lower levels of IFN-γ after LPS stimulation. In PsD, dermatological activity was related with higher IL-17A level, while rheumatic activity was linked with lower levels of IFN-γ and TNFα. Comparing each PsD subtype to HS, IL-1β and IL-6 productions are higher when using LPS stimulation in PsO patients with higher levels of IL-1β and IL-1α in peripheral PsA patients after CD3/CD28 stimulation. LPS stimulation induced high levels of IL-17A in peripheral PsA compared to axial PsA. PsA patients with axial PsA share some features with PsO but shows a distinct cytokine pattern compared to peripheral PsA.ConclusionPsO and the different PsA subtypes exhibit distinct ex vivo cytokine production profiles and common features of the so-called PsD. Analysis of IL-1 cytokine family and IL-6 seems to be of particular interest to distinguish PsO and peripheral PsA since it depends on monocytes in PsO and T-lymphocytes in peripheral PsA. Peripheral cytokine profiles are influenced by rheumatic and dermatological activity of the disease, and also by metabolic syndrome features. Our results highlight the crucial role of immune cell interactions with different patterns of interaction depending on clinical phenotype.
Published: 2022
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3. French hepatitis C care cascade: substantial impact of direct-acting antivirals, but the road to elimination is still long

Author: Cécile Brouard, Josiane Pillonel, Marjorie Boussac, Victor de Lédinghen, Antoine Rachas, Christine Silvain, Nathalie Lydié, Stéphane Chevaliez, Corinne Pioche, Julien Durand, Florence Lot, and Elisabeth Delarocque-Astagneau
Subjects: Hepatitis C, Cascade of care, Elimination, Direct-acting antivirals, Prevalence, Diagnosis, Infectious and parasitic diseases, RC109-216
Abstract: Abstract Background Hepatitis C virus (HCV) elimination by 2030, as targeted by the World Health Organization (WHO), requires that 90% of people with chronic infection be diagnosed and 80% treated. We estimated the cascade of care (CoC) for chronic HCV infection in mainland France in 2011 and 2016, before and after the introduction of direct-acting antivirals (DAAs). Methods The numbers of people (1) with chronic HCV infection, (2) aware of their infection, (3) receiving care for HCV and (4) on antiviral treatment, were estimated for 2011 and 2016. Estimates for 1) and 2) were based on modelling studies for 2011 and on a virological sub-study nested in a national cross-sectional survey among the general population for 2016. Estimates for 3) and 4) were made using the National Health Data System. Results Between 2011 and 2016, the number of people with chronic HCV infection decreased by 31%, from 192,700 (95% Credibility interval: 150,900-246,100) to 133,500 (95% Confidence interval: 56,900-312,600). The proportion of people aware of their infection rose from 57.7 to 80.6%. The number of people receiving care for HCV increased by 22.5% (representing 25.7% of those infected in 2016), while the number of people on treatment increased by 24.6% (representing 12.1% of those infected in 2016). Conclusions This study suggests that DAAs substantially impact CoC. However, access to care and treatment for infected people remained insufficient in 2016. Updating CoC estimates will help to assess the impact of new measures implemented since 2016 as part of the goal to eliminate HCV.
Published: 2020
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4. 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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5. Skin inflammatory response and efficacy of anti-epidermal growth factor receptor therapy in metastatic colorectal cancer (CUTACETUX)

Author: David Tougeron, Sheik Emambux, Laure Favot, Thierry Lecomte, Ewa Wierzbicka-Hainaut, Mahtab Samimi, Eric Frouin, Nicolas Azzopardi, Jocelyn Chevrier, Laura Serres, Julie Godet, Pierre Levillain, Gilles Paintaud, Aurélie Ferru, Laetitia Rouleau, Adriana Delwail, Christine Silvain, Jean-Pierre Tasu, Franck Morel, Stéphanie Ragot, and Jean-Claude Lecron
Subjects: skin toxicity, cetuximab, cytokines, inflammatory factors, monoclonal antibodies, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Anti-epidermal growth factor receptor (EGFR) monoclonal antibody is a standard treatment of metastatic colorectal cancer (mCRC) and its most common adverse effect is a papulopustular acneiform rash. The aim of the CUTACETUX study was to characterize the skin inflammatory response associated with this rash and its relation to treatment efficacy. This prospective study included patients with mCRC treated with first-line chemotherapy plus cetuximab. Patients underwent skin biopsies before the initiation of cetuximab (D0) and before the third infusion (D28), one in a rash zone and one in an unaffected zone. Expression of Th17-related cytokines (IL-17A, IL-21, IL-22), antimicrobial peptides (S100A7 and BD-2), innate response-related cytokines (IL-1β, IL-6, TNF-α and OSM), T-reg-related cytokines (IL-10 and TGF-β), Th1-related cytokine (IFN-γ), Th2-related cytokine (IL-4), Thymic stromal lymphopoietin and keratinocyte-derived cytokines (IL-8, IL-23 and CCL20) were determined by RT-PCR. Twenty-seven patients were included. Levels of most of the cytokines increased at D28 in the rash zone compared to D0. No significant association was observed between variations of cytokines levels and treatment response in the rash zone and only the increase of IL-4 (p = .04) and IL-23 (p = .02) levels between D0 and D28 in the unaffected zone was significantly associated with treatment response. Increased levels of IL-8 (p = .02), BD-2 (p = .02), IL-1β (p = .004) and OSM (p = .02) in the rash zone were associated with longer progression-free survival. Expression of Th2-related and keratinocyte-derived cytokines in the skin was associated with anti-EGFR efficacy. If this inflammatory signature can explain the rash, the exact mechanism by which these cytokines are involved in anti-EGFR tumor response remains to be studied.
Published: 2020
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6. Rapid and large-scale implementation of HCV treatment advances in France, 2007–2015

Author: Cécile Brouard, Marjorie Boussac-Zarebska, Christine Silvain, Julien Durand, Victor de Lédinghen, Josiane Pillonel, and Elisabeth Delarocque-Astagneau
Subjects: Hepatitis C, Treatment, Direct-acting antivirals, Health insurance data, Epidemiology, France, Infectious and parasitic diseases, RC109-216
Abstract: Abstract Background The last decade was marked by major advances in HCV treatment with the introduction of first wave protease inhibitors (1st-wave PIs, telaprevir or boceprevir) in 2011 and second direct-acting antivirals (2nd-wave DAAs) in 2014, that followed low effective pegylated interferon α / ribavirin bitherapy. We estimated the number of patients initiating HCV treatment in France between 2007 and 2015 according to the type of therapy, described their demographical characteristics, and estimated how many were cured with 2nd-wave DAAs in 2014–2015. Methods Individual data from the national health insurance information system were analysed. HCV treatment initiation was defined as a drug reimbursement in the absence of any reimbursement for the same drug in the previous six weeks. Results Between 2007 and 2015, 72,277 patients initiated at least one HCV treatment. The annual number of patients initiating treatment decreased from 2007 (~13,300) to 2010 (~10,000). It then increased with the introduction of 1st-wave PIs (~12,500 in 2012), before decreasing again in 2013 (~8400). A marked increase followed upon the approval of 2nd-wave DAAs in 2014 (~11,600). Approximately, 8700 and 14,700 patients initiated 2nd-wave DAAs in 2014 and 2015, respectively, corresponding to an estimated 20,300 cured patients in 2014–2015. Patients initiating HCV treatment were mostly male (~65% throughout the 9-year period). Women were older than men (mean age: 55.0 vs. 48.9). Increasing age was associated with more advanced treatment. Among patients initiating 2nd-wave DAAs, the proportions of those under 40 and over 79 years old increased between 2014 and 2015, whereas the proportion of those previously treated for HCV 2007 onwards declined. Conclusions Successive advances in HCV treatment have been rapidly and widely implemented in France. With the announcement of universal access to DAAs in mid-2016 and price reductions, access to 2nd-wave DAAs is expected to expand even more.
Published: 2017
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7. Analysis of factors influencing molecular testing at diagnostic of colorectal cancer

Author: Quentin Thiebault, Gautier Defossez, Lucie Karayan-Tapon, Pierre Ingrand, Christine Silvain, and David Tougeron
Subjects: Colorectal cancer, KRAS, Mutation, Molecular testing, BRAF, Microsatellite instability, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background The aim of the study was to evaluate the current rate of molecular testing prescription (KRAS codons 12/13, BRAF and microsatellite instability (MSI)) in newly diagnosed colorectal cancer (CRC) patients and to determine which factors influence testing. Methods All incident CRC cases in 2010 were identified in the Poitou-Charentes General Cancer Registry. The exhaustive molecular testing performed was accessed in the French molecular genetics platform. Factors influencing prescription were analyzed using logistic regression. Results Among the 1269 CRCs included in the study, KRAS, BRAF and MSI testing accounted for 35.1%, 10.5% and 10.9%, respectively. KRAS testing was carried out in 65.5% of metastatic CRCs, and 26.1% of non-metastatic CRCs. Among metastatic CRCs, age (
Published: 2017
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8. Interleukin-1 Family Cytokines: Keystones in Liver Inflammatory Diseases

Author: Louise Barbier, Maroua Ferhat, Ephrem Salamé, Aurélie Robin, André Herbelin, Jean-Marc Gombert, Christine Silvain, and Alice Barbarin
Subjects: interleukin-1 family cytokines, liver diseases, inflammation, innate immunity, trained immunity, invariant natural killer T-cells, Immunologic diseases. Allergy, RC581-607
Abstract: The pyrogenic property being the first activity described, members of the interleukin-1 superfamily (IL-1α, IL-1β, IL-18, and the newest members: IL-33, IL-36, IL-37, and IL-38) are now known to be involved in several inflammatory diseases such as obesity, atherosclerosis, cancer, viral and parasite infections, and auto-inflammatory syndromes as well as liver diseases. Inflammation processes are keystones of chronic liver diseases, of which the etiology may be viral or toxic, as in alcoholic or non-alcoholic liver diseases. Inflammation is also at stake in acute liver failure involving massive necrosis, and in ischemia-reperfusion injury in the setting of liver transplantation. The role of the IL-1 superfamily of cytokines and receptors in liver diseases can be either protective or pro-inflammatory, depending on timing and the environment. Our review provides an overview of current understanding of the IL-1 family members in liver inflammation, highlighting recent key investigations, and therapeutic perspectives. We have tried to apply the concept of trained immunity to liver diseases, based on the role of the members of the IL-1 superfamily, first of all IL-1β but also IL-18 and IL-33, in modulating innate lymphoid immunity carried by natural killer cells, innate lymphoid cells or innate T-αβ lymphocytes.
Published: 2019
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9. 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
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10. Paroxysmal nocturnal hemoglobinuria and vascular liver disease: Eculizumab therapy decreases mortality and thrombotic complications

Author: Aurélie Plessier, Marina Esposito‐Farèse, Anna Baiges, Akash Shukla, Juan Carlos Garcia Pagan, Emmanuelle De Raucourt, Isabelle Ollivier‐Hourmand, Jean‐Paul Cervoni, Victor De Ledinghen, Zoubida Tazi, Jean‐Baptiste Nousbaum, René Bun, Christophe Bureau, Christine Silvain, Olivier Tournilhac, Mathieu Gerfaud‐Valentin, François Durand, Odile Goria, Luis Tellez, Agustin Albillos, Stefania Gioia, Oliviero Riggio, Andrea De Gottardi, Audrey Payance, Pierre‐Emmanuel Rautou, Louis Terriou, Aude Charbonnier, Laure Elkrief, Regis Peffault de la Tour, Dominique‐Charles Valla, Nathalie Gault, and Flore Sicre de Fontbrune
Subjects: Adult, Male, Liver Diseases, Hemoglobinuria, Paroxysmal, Humans, Female, Thrombosis, Hematology, Antibodies, Monoclonal, Humanized, Retrospective Studies
Abstract: A total of 2%-10% of patients with vascular liver disease (VLD) have paroxysmal nocturnal hemoglobinuria (PNH). Eculizumab reduces complement-mediated haemolytic activity in PNH. This study was aimed at assessing the impact of eculizumab on VLD outcome. Retrospective cohort of PNH patients, in Valdig registry, who had VLD diagnosed between 1997 and 2019 is considered. Eculizumab was the exposure of interest. Studied outcomes were death, venous thrombosis, bleeding, arterial ischemic event, infection, and liver-related complications. We compared survival and new thrombotic events from PNH/VLD cohort to Envie2 non-PNH cohort. Sixty-two patients (33 women), median age 35 years (28-48) and median follow-up VLD diagnosis 4.7 years (1.2-9.5), were included. Clone size was 80% (70-90), median hemoglobin concentration was 10.0 g/dl (8-11), and lactate dehydrogenase (LDH) was 736 IU (482-1744). Forty-two patients (68%) had eculizumab; median exposure time was 40.1 [9.3-72.6] months. Mortality was significantly lower in exposed versus nonexposed period: 2.6 versus 8.7 per 100 (PY), incidence rate ratio (IRR) was 0.29, 95% CI (0.1-0.9), p = .035. Thrombosis recurrence occurred less frequently during the exposure to eculizumab: 0.5 versus 2.8 per 100 PY, IRR 0.22 (0.07-0.64). Other secondary end points (i.e., bleeding, arterial ischemic lesions, infection, and liver complications) were less common during the exposure to eculizumab, although not reaching statistical significance. Six-year thrombosis-free survival was 70%, 95% CI [0.60-0.83] for PNH cohort and 83%, 95% CI [0.70-1.00] for non-PNH Envie 2 patients, (p .001). In conclusion, patients with PNH and VLD are at higher risk of recurrent thrombosis than non-PNH patients. Eculizumab is significantly associated with a lower mortality and less thrombotic recurrence in patients with PNH and VLD.
Published: 2022
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11. Validation of a screening algorithm for hepatic fibrosis by Doppler ultrasound and elastography in a general population

Author: Anne-Sophie Renard, Anita Paisant, Victoire Cartier, Paul Calès, Mirela Goyet-Prelipcean, Edmond Geagea, Jean-Pierre Tasu, Christine Silvain, Mathilde Wagner, Aline Le Cleach, Valérie Vilgrain, Laurent Castera, Ivan Bricault, Thomas Decaens, Céline Savoye-Collet, Hélène Montialoux, Jean-Michel Correas, Anaïs Vallet-Pichard, Jérôme Boursier, Christophe Aubé, 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), CH Cholet, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Grenoble, Centre d'Investigation Clinique [Grenoble] (CIC Grenoble), CHU Grenoble-Hôpital Michallon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Université Grenoble Alpes (UGA), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Service de Radiologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Hôpital Cochin [AP-HP], Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Neuro-Radiologie [Angers] (DNR - Angers), and PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)
Subjects: Radiological and Ultrasound Technology, Radiology, Nuclear Medicine and imaging, General Medicine, [SHS]Humanities and Social Sciences
Abstract: Background Early detection can prevent the initial stages of fibrosis from progressing to cirrhosis. Purpose To evaluate an algorithm combining three echographic indicators and elastographic measurements to screen for hepatic fibrosis in an unselected population. Material and Methods From May 2017 to June 2018, all patients with no history and no known chronic liver disease who were referred for an ultrasound (US) were prospectively included in eight hospitals. The indicators being sought were liver surface irregularity, demodulation of hepatic veins, and spleen length >110 mm. Patients presenting at least one of these underwent elastography measurements with virtual touch quantification (VTQ) or supersonic shear imaging (SSI). If elastography was positive, patients were referred to hepatologist for fibrosis evaluation. Reference standard was obtained by FibroMeterVCTE or biopsy. A FibroMeterVCTE result >0.384 indicated a “necessary referral” to a hepatologist. Results Of the 1501 patients included, 504 (33.6%) were positive for at least one US indicator. All of them underwent US elastography, with 85 being positive. Of the patients, 58 (3.6%) had a consultation with a liver specialist: 21 had positive FibroMeterVCTE and nine had an indication of biopsy for suspicion of fibrosis. This screening algorithm made it possible to diagnose 1.6% of patients in our population with unknown fibrosis. Of the patients, 50% referred to the liver specialist were “necessary referrals.” Conclusion Our study suggests that three simple US indicators with no systematic elastographic measurement could be applied in day-to-day practice to look for hepatic fibrosis in an unsuspected population allowing relevant referrals to a hepatologist.
Published: 2023
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12. Health-related quality of life in locally advanced hepatocellular carcinoma treated by either radioembolisation or sorafenib (SARAH trial)

Author: Helena Pereira, Mohamed Bouattour, Marco D. Burgio, Eric Assenat, Jules Grégory, Jean-Pierre Bronowicki, Gilles Chatellier, Valérie Vilgrain, Elisabeth Delhom-Christol, Marjolène Fourcade, Boris Guiu, Alina Diana Ilonca, Julie Lonjon, Georges-Philippe Pageaux, Mohamed Abdel-Rehim, Wassim Allaham, Laurent Castera, Arnaud Dieudonné, Rachida Lebtahi, Maxime Ronot, Annie Sibert, Hélène Chor, Julie Devictor, Hélène Barraud, Christophe Bazin, Laetitia Imbert, Valérie Laurent, Elodie Mathias, Carine Chagneau-Derrode, Christelle Gallais, Rémy Perdrisot, Christine Silvain, Jean Pierre Tasu, Patrick Borentain, Bardia Farman, René Gerolami, Olivier Mundler, Jean-Francois Seitz, Vincent Vidal, Christophe Aubé, Francis Bouchet, Antoine Bouvier, Olivier Couturier, Frédéric Oberti, Laurent Vervueren, Isabelle Brenot-Rossi, Julien Darreon, Jean Luc Raoul, Anthony Sarran, Julia Chalaye, Charlotte Costentin, Emmanuel Itti, Hicham Kobeiter, Alain Luciani, Hélène Masset, René Adam, Maïté Lewin, Didier Samuel, Julien Edeline, Etienne Garin, Sophie Laffont, Yan Rolland, Isabelle Archambeaud, Thomas Carlier, Thomas Eugene, Eric Frampas, Christophe Cassinotto, Martine Guyot, Jean-Baptiste Hiriart, Bruno Lapuyade, Karine Tendero, Julien Vergniol, Philippe Bachellier, Julien Détour, Bernard Duclos, Michel Greget, Francois Habersetzer, Alessio Imperiale, Elise Enderlin, Philippe Merle, Agnès Rode, Julie Morvan, Eric Nguyen-Khac, Antoine Talbot, Thierry Yzet, Guillaume Baudin, Patrick Chevallier, Abakar Mahamat, Fabien Maurel, Thierry Piche, Micheline Razzouk, Patrick Hillon, Romaric Loffroy, Michel Toubeau, Julie Vincent, Jean-Marc Vrigneaud, Gabriele Barabino, Nadia Bouarioua, Muriel Cuilleron, Marie Ecochard, Nathalie Prevot-Bitot, Evelyne Rousset, Vincent Leroy, Ghislaine Reboulet, Julie Roux, Christian Sengel, Valérie Bourcier, Nathalie Ganne-Carrie, Olivier Seror, Sylvie Costo, Thông Dao, Cédric Desmonts, Jean-Pierre Pelage, Didier Defez, Jérôme Dumortier, Francesco Giammarile, Pierre-Jean Valette, Michela Bernardini, Nadia Ghazar, Olivier Pellerin, Julien Taieb, Pierre Weinmann, Alexandra Heurgue-Berlot, Claude Marcus, Daniele Sommacale, Maria-Angéla Castilla-Lièvre, Aurélie Forbes, Sophie Maitre, Lysiane Marthey, CIC - HEGP (CIC 1418), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Equipe IFTIM [ImViA - EA7535], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Imagerie et Vision Artificielle [Dijon] (ImViA), and Université de Bourgogne (UB)-Université de Bourgogne (UB)
Subjects: Male, Sorafenib, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, Tare weight, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Locally advanced, Quality of life, Internal medicine, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Aged, Social functioning, Health related quality of life, business.industry, Liver Neoplasms, Middle Aged, medicine.disease, Embolization, Therapeutic, digestive system diseases, Confidence interval, Oncology, Hepatocellular carcinoma, Quality of Life, Female, business, medicine.drug
Abstract: Background The aim of this ancillary study of the SARAH trial is to compare health-related quality of life (HRQoL) in patients with locally advanced or inoperable hepatocellular carcinoma (HCC) treated with transarterial radioembolisation (TARE) or sorafenib. Methods This study included randomised patients who received either TARE or at least one dose of sorafenib with no major deviation in the protocol and who had at least one QoL follow-up assessment in addition to the baseline evaluation. QoL was assessed from the date of randomisation using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire, until disease progression or other reasons for stopping study participation. Data were analysed using linear mixed and time-dependent models. Results A total of 285 patients were included (122 and 163, in the TARE and sorafenib groups, respectively). Questionnaire completion rates were similar (77.5% versus 80.4%, in the TARE and sorafenib groups, respectively, p = 0.25). Longitudinal HRQoL analysis showed a significant treatment and time effects for fatigue and global health status, and significant treatment, time and treatment by time interaction effects for appetite loss, diarrhoea and social functioning. The median time to deterioration for the global health status was 3.9 months (95% confidence interval [CI] 3.7–4.3) versus 2.6 months (95% CI 2.0–3.0) in the TARE and sorafenib groups, respectively. Conclusions HRQoL was preserved longer with TARE than with sorafenib in locally advanced HCC. These data could be used to optimise management of patients with advanced or inoperable HCC.
Published: 2021
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13. HCV eradication does not protect from fibrosis progression in patients with fibrosing cholestatic hepatitis after liver transplantation

Author: Audrey, Coilly, Mylène, Sebagh, Claire, Fougerou-Leurent, Georges-Philippe, Pageaux, Vincent, Leroy, Sylvie, Radenne, Christine, Silvain, Pascal, Lebray, Pauline, Houssel-Debry, Carole, Cagnot, Emilie, Rossignol, Hélène, Danjou, Aurélie, Veislinger, Didier, Samuel, Jean-Charles, Duclos-Vallée, Jérôme, Dumortier, Hôpital Paul Brousse, Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Dynamique des systèmes d'adhérence et différenciation (DySAD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Albert Bonniot, Hospices Civils de Lyon, Departement de Neurologie (HCL), Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Hospices Civils de Lyon (HCL), and The study was sponsored and funded by The National Agency for Research on AIDS and Viral Hepatitis (ANRS, France Recherche Nord&sud Sida-hiv Hépatites).
Subjects: Liver Cirrhosis, Liver transplantation, Hepatology, Cholangitis, Fibrosing cholestatic hepatitis, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepacivirus, Hepatitis C, Chronic, Antiviral Agents, Hepatitis C, Fibrosis, Treatment, Recurrence, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, HCV, Pathology, Humans, Retrospective Studies
Abstract: International audience; INTRODUCTION: Hepatitis C virus (HCV) may recur after liver transplantation (LT) in the severe form of fibrosing cholestatic hepatitis (FCH). The prognosis dramatically improved by the use of direct acting antivirals (DAAs). The aim of the present study was to describe the change in histological features of FCH after virological eradication. METHODS: From the ANRS CUPILT cohort we included 17 patients who presented FCH and at least two graft biopsies, one before DAA-treatment and one after. A single expert pathologist, blinded for clinical outcome, retrospectively confirmed the diagnosis of FCH and progression of fibrosis. RESULTS: Diagnosis of FCH was made after a median [IQR] 6.0 [3.1-11.8] months after LT, and the median interval between diagnosis and onset of treatment was 1.2 [0.7-6.1] months. The rate of viral eradication was 94.1%. The median delay between the pre-treatment and the treatment biopsies was 12.5 [11.1-20.0] months. Between the end of treatment and the second biopsy, the delay was 5.3 [0.6-7.4] months. Fibrosis stage worsened in 10 patients (58.8%); 6 patients had cirrhosis (35.3%). Chronic rejection appeared in 4 (23.5%) patients. CONCLUSION: Our results suggest that, despite viral eradication in patients presenting FCH after LT, fibrosis progression was observed in half of patients. This should encourage monitoring fibrosis progression despite HCV cure.
Published: 2022
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14. Early liver transplantation for corticosteroid non-responders with acute severe autoimmune hepatitis: The SURFASA score

Author: Olivier Chazouillères, Florent Artru, Eleonora De Martin, Philippe Mathurin, Camille Besch, Christophe Duvoux, François Durand, Odile Goria, Hélène Fontaine, Hélène Agostini, Isabelle Ollivier-Hourmand, Noemi Reboux, Olivier Roux, Filomena Conti, Nathalie Ganne-Carrié, Didier Samuel, Georges-Philippe Pageaux, Philippe Ichai, Marilyne Debette-Gratien, Christine Silvain, Alexandra Heurgue, Jean-Marie Peron, Sylvie Radenne, Jérôme Dumortier, Audrey Coilly, Pauline Houssel-Debry, Sandrine Barge, Marc Bourlière, Pascal Potier, Jean-Charles Duclos-Vallée, Vincent Di Martino, Mylène Sebagh, and Victor de Ledinghen
Subjects: 0301 basic medicine, medicine.medical_specialty, Multivariate analysis, Hepatology, medicine.drug_class, Bilirubin, business.industry, medicine.medical_treatment, Odds ratio, Autoimmune hepatitis, Liver transplantation, medicine.disease, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, chemistry, Internal medicine, medicine, Corticosteroid, 030211 gastroenterology & hepatology, Prospective cohort study, business, Survival rate
Abstract: Background & Aims In acute severe autoimmune hepatitis (AS-AIH), the optimal timing for liver transplantation (LT) remains controversial. The objectives of this study were to determine early predictive factors for a non-response to corticosteroids and to propose a score to identify patients in whom LT is urgently indicated. Methods This was a retrospective, multicenter study (2009-2016). A diagnosis of AS-AIH was based on: i) Definite or probable AIH based on the simplified IAIHG score; ii) international normalized ratio (INR) ≥1.5 and/or bilirubin >200 μmol/L; iii) No previous history of AIH; iv) Histologically proven AIH. A treatment response was defined as LT-free survival at 90 days. The evolution of variables from corticosteroid initiation (day-D0) to D3 was estimated from: Δ%3 = (D3–D0)/D0. Results A total of 128 patients were included, with a median age of 52 (39–62) years; 72% were female. Overall survival reached 88%. One hundred and fifteen (90%) patients received corticosteroids, with a LT-free survival rate of 66% at 90 days. Under multivariate analysis, D0-INR (odds ratio [OR] 6.85; 95% CI 2.23–21.06; p Conclusion In patients with AS-AIH, INR at the introduction of corticosteroids and the evolution of INR and bilirubin are predictive of LT or death. Within 3 days of initiating corticosteroids, the SURFASA score can identify non-responders who require a referral for LT. This score needs to be validated in a prospective cohort. Lay summary The management of patients with acute severe autoimmune hepatitis is highly challenging, particularly regarding their early referral for liver transplantation. We found that international normalized ratio at the initiation of corticosteroid therapy and the evolution of international normalized ratio and bilirubin values after 3 days of therapy were highly predictive of liver transplantation or death. We are thus proposing a score that combines these variables and identifies patients in whom liver transplantation is urgently required.
Published: 2021
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15. French hepatitis C care cascade: substantial impact of direct-acting antivirals, but the road to elimination is still long

Author: Josiane Pillonel, A Rachas, Elisabeth Delarocque-Astagneau, Cécile Brouard, Nathalie Lydié, Christine Silvain, Marjorie Boussac, Corinne Pioche, Florence Lot, Julien Durand, Victor de Ledinghen, Stéphane Chevaliez, Direction des maladies infectieuses - Infectious Diseases Division [Saint-Maurice], Santé publique France - French National Public Health Agency [Saint-Maurice, France], Caisse Nationale de l'Assurance Maladie [Paris] (CNAM), 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), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre National de Référence Virus des hépatites B, C et Delta, Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (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), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Raymond Poincaré [AP-HP], To all the people who contributed to producing the estimates used in this work: JC. Desenclos, A. Gautier, M. Jauffret-Roustide, C. Larsen, Y. Le Strat, C. Pelat, D. Rahib, JB. Richard, L. Saboni, C. Sommen (Sant? publique France), and F. Barin (National Reference Centre for HIV), C. Gastaldi-M?nager, T. Lesuffleur (Cnam) and the infectious work-group of the ReDSIAM. To Jude Sweeney for the English revision of the manuscript.
Subjects: Adult, Male, Health Knowledge, Attitudes, Practice, medicine.medical_specialty, Adolescent, Cascade of care, Elimination, Hepatitis C virus, Population, medicine.disease_cause, Direct-acting antivirals, Antiviral Agents, lcsh:Infectious and parasitic diseases, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Medical microbiology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Diagnosis, Credible interval, medicine, Prevalence, Humans, lcsh:RC109-216, 030212 general & internal medicine, education, Aged, Aged, 80 and over, education.field_of_study, business.industry, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, Confidence interval, Management, 3. Good health, Treatment, Chronic infection, Cross-Sectional Studies, Infectious Diseases, Tropical medicine, Female, 030211 gastroenterology & hepatology, France, business, Research Article
Abstract: Background Hepatitis C virus (HCV) elimination by 2030, as targeted by the World Health Organization (WHO), requires that 90% of people with chronic infection be diagnosed and 80% treated. We estimated the cascade of care (CoC) for chronic HCV infection in mainland France in 2011 and 2016, before and after the introduction of direct-acting antivirals (DAAs). Methods The numbers of people (1) with chronic HCV infection, (2) aware of their infection, (3) receiving care for HCV and (4) on antiviral treatment, were estimated for 2011 and 2016. Estimates for 1) and 2) were based on modelling studies for 2011 and on a virological sub-study nested in a national cross-sectional survey among the general population for 2016. Estimates for 3) and 4) were made using the National Health Data System. Results Between 2011 and 2016, the number of people with chronic HCV infection decreased by 31%, from 192,700 (95% Credibility interval: 150,900-246,100) to 133,500 (95% Confidence interval: 56,900-312,600). The proportion of people aware of their infection rose from 57.7 to 80.6%. The number of people receiving care for HCV increased by 22.5% (representing 25.7% of those infected in 2016), while the number of people on treatment increased by 24.6% (representing 12.1% of those infected in 2016). Conclusions This study suggests that DAAs substantially impact CoC. However, access to care and treatment for infected people remained insufficient in 2016. Updating CoC estimates will help to assess the impact of new measures implemented since 2016 as part of the goal to eliminate HCV.
Published: 2020
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16. Evaluation of Longitudinal Exposure to Tacrolimus as a Risk Factor of Chronic Kidney Disease Occurrence Within the First-year Post-Liver Transplantation

Author: Paul Carrier, Ephrem Salamé, Annick Rousseau, Marie Essig, Louise Barbier, Jérémie Jacques, Pauline Maurel, Véronique Loustaud-Ratti, Xavier Causse, Christine Silvain, Pierre Marquet, Aurélie Prémaud, and Marilyne Debette-Gratien
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, Renal function, 030230 surgery, Kidney, urologic and male genital diseases, Risk Assessment, Gastroenterology, Disease-Free Survival, Tacrolimus, 03 medical and health sciences, 0302 clinical medicine, Hepatorenal syndrome, Risk Factors, Internal medicine, Humans, Medicine, Renal Insufficiency, Chronic, Risk factor, Aged, Retrospective Studies, Transplantation, business.industry, Hazard ratio, Acute kidney injury, Acute Kidney Injury, Middle Aged, medicine.disease, female genital diseases and pregnancy complications, Liver Transplantation, Calcineurin, Female, 030211 gastroenterology & hepatology, business, Immunosuppressive Agents, Glomerular Filtration Rate, Kidney disease
Abstract: BACKGROUND Renal failure is predictive of mortality in the early postliver-transplantation period and calcineurin inhibitors toxicity is a main challenge. Our aim is to assess the impact of longitudinal tacrolimus exposure (TLE) and other variables on chronic kidney disease (CKD)-free 1-year-survival. METHODS Retrospective data of consecutive patients transplanted between 2011 and 2016 and treated with tacrolimus were collected. TLE and all relevant pre- and post-liver transplantation (LT) predictive factors of CKD were tested and included in a time-to-event model. CKD was defined by repeated estimated glomerular filtration rate (eGFR) values below 60 mL/min/1.73m2 at least for the last 3 months before M12 post-LT. RESULTS Data from 180 patients were analyzed. CKD-free survival was 74.5% and was not associated with TLE. Pre-LT acute kidney injury (AKI) and eGFR at 1-month post-LT (eGFRM1)
Published: 2020
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17. Early liver transplantation for severe alcohol-related hepatitis not responding to medical treatment: a prospective controlled study

Author: Alexandre Louvet, Julien Labreuche, Christophe Moreno, Claire Vanlemmens, Romain Moirand, Cyrille Féray, Jérôme Dumortier, Georges-Philippe Pageaux, Christophe Bureau, Faïza Chermak, Christophe Duvoux, Dominique Thabut, Vincent Leroy, Nicolas Carbonell, Benjamin Rolland, Ephrem Salamé, Rodolphe Anty, Jérôme Gournay, Jean Delwaide, Christine Silvain, Valerio Lucidi, Guillaume Lassailly, Sébastien Dharancy, Eric Nguyen-Khac, Didier Samuel, Alain Duhamel, Philippe Mathurin, Christophe Berthot, Sylvie Claudet, Alexandre Doussot, Caroline Gérardin, Emilie Muel, Jean-Baptiste Hiriart, Delphine Degré, Thierry Gustot, Agnès Bonadona, Laure Bordy, Marie-Noelle Hilleret, Olivier Detry, Pierre Honoré, Nicolas Meurisse, Emmanuel Boleslawski, Dominique Deplanque, Mehdi El Amrani, Gilles Lebuffe, Guillaume Millet, Daphnée Soret, Stéphanie Truant, Domitille Erard-Poinsot, Sylvie Radenne, Stéphanie Faure, Eve Gelsi, Régine Truchi, Marika Rudler, Laëtitia Rouleau, Audrey Brenner, Hélène Larrue, Jean-Marie Péron, Marie-Angèle Robic, Teresa Antonini, Jean-Charles Duclos-Vallée, CHU Lille, Université libre de Bruxelles (ULB), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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), CHU Grenoble, Centre Hospitalier le Vinatier [Bron], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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 Nantes (CHU Nantes), Centre Hospitalier Universitaire de Liège (CHU-Liège), Centre hospitalier universitaire de Poitiers (CHU Poitiers), 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), Hôpital Claude Huriez [Lille], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hôpital JeanMinjoz, 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), 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), CHU Toulouse [Toulouse], CHU Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], 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 de Référence des Maladies Rares - Maladies Inflammatoires des Voies Biliaires et Service d’Hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Service Universitaire d’Addictologie de Lyon [CH Le Vinatier, Bron] (Pôle MOPHA - SUAL), CHU Trousseau [Tours], Hôpital Archet 2 [Nice] (CHU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), and Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: surgical procedures, operative, Hepatology, Hepatitis, Alcoholic, Liver Cirrhosis, Alcoholic, [SDV]Life Sciences [q-bio], Gastroenterology, Humans, Prospective Studies, Neoplasm Recurrence, Local, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Liver Transplantation
Abstract: International audience; BACKGROUND: Early liver transplantation for severe alcohol-related hepatitis is an emerging treatment option. We aimed to assess the risk of alcohol relapse 2 years after early liver transplantation for alcohol-related hepatitis compared with liver transplantation for alcohol-related cirrhosis after at least 6 months of abstinence. METHODS: We conducted a multicentre, non-randomised, non-inferiority, controlled study in 19 French and Belgian hospitals. All participants were aged 18 years or older. There were three groups of patients recruited prospectively: patients with severe alcohol-related hepatitis who did not respond to medical treatment and were eligible for early liver transplantation according to a new selection scoring system based on social and addiction items that can be quantified in points (early transplantation group); patients with alcohol-related cirrhosis listed for liver transplantation after at least 6 months of abstinence (standard transplantation group); patients with severe alcohol-related hepatitis not responding to medical treatment not eligible for early liver transplantation according to the selection score (not eligible for early transplantation group), this group did not enter any further liver transplantation processes. We also defined a historical control group of patients with severe alcohol-related hepatitis unresponsive to medical therapy and non-transplanted. The primary outcome was the non-inferiority of 2-year rate of alcohol relapse after transplantation in the early transplantation group compared with the standard transplantation group using the alcohol timeline follow back (TLFB) method and a prespecified non-inferiority margin of 10%. Secondary outcomes were the pattern of alcohol relapse, 2-year survival rate post-transplant in the early transplantation group compared with the standard transplantation group, and 2-year overall survival in the early transplantation group compared with patients in the not eligible for early transplantation group and historical controls. This trial is registered with ClinicalTrials.gov, NCT01756794. FINDINGS: Between Dec 5, 2012, and June 30, 2016, we included 149 patients with severe alcohol-related hepatitis: 102 in the early transplantation group and 47 in the not eligible for early transplantation group. 129 patients were included in the standard transplantation group. 68 patients in the early transplantation group and 93 patients in the standard transplantation group received a liver transplant. 23 (34%) patients relapsed in the early transplantation group, and 23 (25%) patients relapsed in the standard transplantation group; therefore, the non-inferiority of early transplantation versus standard transplantation was not demonstrated (absolute difference 9·1% [95% CI -∞ to 21·1]; p=0·45). The 2-year rate of high alcohol intake was greater in the early transplantation group than the standard transplantation group (absolute difference 16·7% [95% CI 5·8-27·6]) The time spent drinking alcohol was not different between the two groups (standardised difference 0·24 [95% CI -0·07 to 0·55]), but the time spent drinking a large quantity of alcohol was higher in the early transplantation group than the standard transplantation group (standardised difference 0·50 [95% CI 0·17-0·82]). 2-year post-transplant survival was similar between the early transplantation group and the standard transplantation group (hazard ratio [HR] 0·87 [95% CI 0·33-2·26]); 2-year overall survival was higher in the early transplantation group than the not eligible for early transplantation group and historical controls (HR 0·27 [95% CI 0·16-0·47] and 0·21 [0·13-0·32]). INTERPRETATION: We cannot conclude non-inferiority in terms of rate of alcohol relapse post-transplant between early liver transplantation and standard transplantation. High alcohol intake is more frequent after early liver transplantation. This prospective controlled study confirms the important survival benefit related to early liver transplantation for severe alcohol-related hepatitis; and this study provides objective data on survival and alcohol relapse to tailor the management of patients with severe alcohol-related hepatitis. FUNDING: The present study has been granted by the French Ministry of Health-Programme Hospitalier de Recherche Clinique 2010.
Published: 2022
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18. Male gender is associated with informal caregiver burden in patients with chronic intestinal failure treated with home parenteral nutrition

Author: Jean Castinel, Gauthier Pellet, David Laharie, Frank Zerbib, Christine Silvain, Eva Wilsius, Laurianne Kerlogot, Pauline Rivière, and Florian Poullenot
Subjects: Male, Nutrition and Dietetics, Medicine (miscellaneous), Caregiver Burden, Middle Aged, Intestinal Failure, Intestinal Diseases, Caregivers, Chronic Disease, Quality of Life, Humans, Female, Prospective Studies, Parenteral Nutrition, Home
Abstract: Home parenteral nutrition (HPN) is the recommended treatment in patients with chronic intestinal failure (CIF). HPN is associated with a worsening of patients' quality of life and has a dramatic impact on personal and familial daily life. Little is known about the informal caregiver burden of patients receiving HPN.To assess informal caregiver burden and the factors associated with moderate-to-severe caregiver burden in patients treated with HPN.Informal caregivers of consecutive patients treated with HPN in a French nutrition referral center were invited to participate in a survey between January 2021 and June 2021. They had to fill out an anonymous standardized self-questionnaire evaluating burden by the Zarit Burden Interview (ZBI) and depression and anxiety symptoms by the Hospital Anxiety and Depression Scale (HADS) score since HPN introduction.Among the 87 HPN patients having informal caregivers, 53 (61%) completed the questionnaire. Thirty (57%) informal caregivers were women. The caregiver's median age was 62 years (IQR, 21.0). Twelve (22%) expressed moderate to severe burden (ZBI score, 41-88). In a multivariate analysis, the caregiver's male gender (odds ratio [OR], 16.45; 95% CI, 2.30-238.75; P = 0.014) and the number of simultaneous infusions per day1 (OR, 9.92; 95% CI, 1.35-121.60; P = 0.0038) were associated with a moderate to severe burden. Twenty caregivers reported anxious and depressive symptoms with an elevated HADS score.In this prospective survey, a minority of informal caregivers of patients with CIF being treated with HPN expressed moderate to severe burden. The caregiver's male gender was associated with a higher burden in patients with CIF.
Published: 2022

19. Overexpression of IgG2 in patients resembling IgG4-related disease with normal IgG4

Author: Mathilde Lecuit, Pierre Aucouturier, Aicha Abbas, Jacques Cadranel, Christine Silvain, Jean‐Marie Berthelot, Anne‐Laure Fauchais, Paul Loubet, Claude Bachmeyer, Françoise Montravers, Antoine Dossier, Hilario Nunes, Pascale Cervera, and Paul Coppo
Subjects: Adult, Aged, 80 and over, Male, Biopsy, Immunology, Plasma Cells, General Medicine, Middle Aged, Immunoglobulin G, Humans, Female, Immunoglobulin G4-Related Disease, Lymph Nodes, Aged, Retrospective Studies
Abstract: IgG4-Related Disease (IgG4-RD) results from tissue infiltration by IgG4-expressing plasma cells and lymphocytes, leading to fibrosis and organomegaly. Clinical presentation is remarkably variable according to organ involvement, and high IgG4 serum concentration, initially considered a diagnostic hallmark of IgG4-RD, tends to be forgone as an indispensable criterion for its diagnosis; it can indeed be absent in some patients, highlighting the diversity of presentation of this dysimmune condition. Nevertheless, elevation of IgG4 serum concentration in suggestive settings remains an argument in favour of IgG4-RD, and while other IgG subclasses can be elevated, this biological feature lacks any diagnostic value. We retrospectively studied 9 patients (5 females, 4 males, 31-81 years old) for whom a diagnosis of IgG4-RD had been considered, based on clinical, imaging or histological criteria, but appeared to display abnormally high serum IgG2 while IgG4 levels were normal. Increased serum IgG1 in one case and increased IgG3 in another one were also noticed. Immunohistochemical analyses of intracellular immunoglobulins could be performed on tissue lymph node biopsies from 2 patients, which demonstrated strong infiltration with IgG2-expressing plasma cells. Thus, overexpression of IgG2 subclass may highlight cases of dysimmune disorders resembling IgG4-RD, although the disease trigger might be different, notably infectious. We suggest measuring all serum IgG subclass levels in patients with features consistent with IgG4-RD.
Published: 2021

20. Cost-Utility Analysis of Transarterial Radioembolization With Yttrium-90 Resin Microspheres Compared With Sorafenib in Locally Advanced and Inoperable Hepatocellular Carcinoma

Author: Kevin Zarca, Maroua Mimouni, Helena Pereira, Gilles Chatellier, Valérie Vilgrain, Isabelle Durand-Zaleski, Eric Assenat, Elisabeth Delhom-Christol, Boris Guiu, Alina D. Ilonca, Julie Lonjon, Georges-Philippe Pageaux, Mohamed Abdel-Rehim, Wassim Al-laham, Mohamed Bouattour, Laurent Castera, Arnaud Dieudonné, Rachida Lebtahi, Maxime Ronot, Annie Sibert, Hélène Barraud, Christophe Bazin, Jean-Pierre Bronowicki, Valérie Laurent, Elodie Mathias, Carine Chagneau-Derrode, Rémy Perdrisot, Christine Silvain, Jean-Pierre Tasu, Patrick Borentain RenéGerolami, Olivier Mundler, Jean-Francois Seitz, Vincent Vidal, Christophe Aubé, Antoine Bouvier, Olivier Couturier, Frédéric Oberti, Laurent Vervueren, Isabelle Brenot-Rossi, Jean-Luc Raoul, Anthony Sar-ran, Julia Chalaye, Charlotte Costentin, Emmanuel Itti, Hicham Kobeiter, Alain Luciani, René Adam, Maïté Lewin, Didier Samuel, Julien Edeline, Etienne Garin, Yan Rolland, Isabelle Archambeaud, Thomas Eugene, Eric Frampas, Christophe Cassinotto, Martine Guyot, Jean-Baptiste Hiriart, Bruno Lapuyade, Julien Vergniol, Philippe Bachellier, Julien Detour, Bernard Duclos, Michel Greget, Francois Habersetzer, Alessio Imperiale, Philippe Merle, Agnès Rode, Julie Morvan, Eric Nguyen-Khac, Thierry Yzet, Guillaume Baudin, Patrick Chevallier, Abakar Mahamat, Thierry Piche, Micheline Razzouk, Patrick Hillon, Romaric Loffroy, Michel Toubeau, Julie Vincent, Gabriele Barabino, Nadia Bouarioua, Muriel Cuilleron, Marie Ecochard, Nathalie Prevot-Bitot, Vincent Leroy, Julie Roux, Christian Sengel, Valérie Bourcier, Nathalie Ganne- Carrie, Olivier Seror, Sylvie Costo, Thông Dao, Jean-Pierre Pelage, Jérôme Dumortier, Francesco Giammarile, Pierre-Jean Valette, Nadia Ghazzar, Olivier Pellerin, Julien Taieb, Pierre Weinmann, Alexandra Heurgue- Berlot, Claude Marcus, Daniele Sommacale, Maria-Angéla Castilla-Lièvre, Sophie Maitre, Lysiane Marthey, Direction de la Recherche Clinique et de l'Innovation [AP-HP] (DRCI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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), CIC - HEGP (CIC 1418), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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), 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), Département radiologie diagnostique et interventionnelle Saint Eloi [CHRU Montpellier], Pôle Digestif [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Equipe IFTIM [ImViA - EA7535], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Imagerie et Vision Artificielle [Dijon] (ImViA), Université de Bourgogne (UB)-Université de Bourgogne (UB), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and CHU Saint-Eloi-Université de Montpellier (UM)
Subjects: Sorafenib, Oncology, medicine.medical_specialty, Randomization, Carcinoma, Hepatocellular, Tare weight, Hepatocellular carcinoma, Cost-Benefit Analysis, [SDV.CAN]Life Sciences [q-bio]/Cancer, 02 engineering and technology, 030204 cardiovascular system & hematology, Transarterial Radioembolization, 03 medical and health sciences, 020210 optoelectronics & photonics, 0302 clinical medicine, Quality of life, Internal medicine, 0202 electrical engineering, electronic engineering, information engineering, medicine, Humans, Pharmacology (medical), Yttrium radioisotopes, Survival analysis, Pharmacology, Cost–utility analysis, business.industry, Liver Neoplasms, Cost-utility analysis, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, Microspheres, Quality of Life, business, medicine.drug
Abstract: International audience; Purpose: The SARAH (Sorafenib Versus Radioembolization in Advanced Hepatocellular Carcinoma) trial (ClinicalTrials.gov Identifier NCT01482442) did not show a significant survival benefit for patients treated with transarterial radioembolization (TARE) compared with continuous oral sorafenib. The improved toxicity profile of patients treated with TARE in the trial, however, could result in a quality of life benefit in economic evaluations. Our objective was to perform a cost-utility analysis of TARE versus sorafenib for locally advanced and inoperable hepatocellular carcinoma.Methods: This study used patient-level data of the SARAH trial regarding resource use, progression-free and overall survival, and quality of life for the within-trial period for the patients who received at least 1 dose of sorafenib or 1 treatment with TARE according to their randomization arm. Data were extrapolated by using a partitioned survival model that incorporated costs and health outcomes, measured in life-years and quality-adjusted life-years (QALYs).Findings: The use of TARE resulted in an average loss of 0.036 life-year and a gain of 0.006 QALY compared with sorafenib. The aerage cost for the TARE arm was €17,179 (95% CI, 9,926-24,280) higher than the sorafenib arm, for an incremental cost-effectiveness ratio of €3,153,086/QALY. The probabilistic sensitivity analysis revealed a 50% risk that the TARE strategy was dominated. TARE was consistently dominated by sorafenib or had an incremental cost-effectiveness ratio more than €450,000/QALY in all sensitivity analyses.Implications: This economic evaluation of SARAH found that using radioembolization with yttrium-90 microspheres for the treatment of hepatocellular carcinoma was not a cost-effective option at the usually accepted willingness-to-pay thresholds.
Published: 2021
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21. 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
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22. Combination of fibrates with obeticholic acid is able to normalise biochemical liver tests in patients with difficult-to-treat primary biliary cholangitis

Author: Pietro Invernizzi, Dominique Larrey, Thomas Berg, Christine Silvain, Christina Weiler-Normann, Rodolphe Anty, Cervoni Jp, Albert Parés, Cynthia Levy, Olivier Chazouillères, Laurent Lam, Christophe Bureau, Isabelle Rosa-Hezode, Palak J. Trivedi, Christoph Schramm, Nora Cazzagon, Laurent Alric, Vincent Leroy, Alexandra Heurgué, Frederik Nevens, Jérôme Dumortier, Pierre Antoine Soret, Olivier Roux, Marco Carbone, Fabrice Carrat, Pascal Potier, Lena Smets, Christophe Corpechot, Gestionnaire, Hal Sorbonne Université, Centre de Référence des Maladies Rares - Maladies Inflammatoires des Voies Biliaires et Service d’Hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), 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], University Hospitals Leuven [Leuven], Leipzig University, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Centre Hospitalier Universitaire [Grenoble] (CHU), University Hospitals Birmingham [Birmingham, Royaume-Uni], Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Centre Hospitalier Intercommunal de Créteil (CHIC), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Régional d'Orléans (CHRO), Centre de référence des Maladies Vasculaires du Foie [Paris] (FILFOIE), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), University of Miami Leonard M. Miller School of Medicine (UMMSM), Clinic Barcelona Hospital Universitari, Soret, P, Lam, L, Carrat, F, Smets, L, Berg, T, Carbone, M, Invernizzi, P, Leroy, V, Trivedi, P, Cazzagon, N, Weiler-Normann, C, Alric, L, Rosa-Hezode, I, Heurgue, A, Cervoni, J, Dumortier, J, Potier, P, Roux, O, Silvain, C, Bureau, C, Anty, R, Larrey, D, Levy, C, Pares, A, Schramm, C, Nevens, F, Chazouilleres, O, and Corpechot, C
Subjects: Liver Cirrhosis, medicine.medical_specialty, Cholagogues and Choleretics, Bilirubin, [SDV]Life Sciences [q-bio], Chenodeoxycholic Acid, Gastroenterology, chemistry.chemical_compound, Retrospective Studie, Internal medicine, Chenodeoxycholic acid, medicine, Humans, Pharmacology (medical), Cholagogues and Choleretic, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Bezafibrate, Fenofibrate, Hepatology, Liver Cirrhosis, Biliary, business.industry, Fibric Acids, Ursodeoxycholic Acid, Biliary, Obeticholic acid, Retrospective cohort study, Odds ratio, eye diseases, Ursodeoxycholic acid, Fibric Acid, [SDV] Life Sciences [q-bio], chemistry, business, Human, medicine.drug
Abstract: Background: Obeticholic acid (OCA) and fibrates are second-line therapies for patients with primary biliary cholangitis (PBC) with an inadequate response to ursodeoxycholic acid (UDCA). Aim: To know whether OCA and fibrates, administered together in combination with UDCA, have additive beneficial effects in patients with difficult-to-treat PBC. Methods: PBC patients treated for ≥3months with UDCA, OCA and fibrates (bezafibrate or fenofibrate) due to failure of either second-line therapy were included in a multicentre, uncontrolled retrospective cohort study. Changes in biochemical liver tests and pruritus were analysed using a generalised linear mixed-effect model. Results: Among 58 patients included, half received OCA as second-line and fibrates as third-line therapy (Group OCA-Fibrate), while the other half had the inverse therapeutic sequence (Group Fibrate-OCA). The mean duration of triple therapy was 11months (range 3-26). Compared to dual therapy, triple therapy was associated with a significant gain in alkaline phosphatase (ALP) reduction: 22% per first year (95% CI 12%-31%), an effect that was stronger in OCA-Fibrate than in Fibrate-OCA group. Triple therapy was associated with a 3.4 (95% CI 1.4-8.2) odds ratio (OR) of reaching normal ALP and with a significant decrease in gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin. The ORs of achieving the Paris-2 and Toronto criteria of adequate biochemical response were 6.8 (95% CI 2.8-16.7) and 9.2 (95% CI 3.4-25.1) respectively. Finally, triple therapy significantly improved pruritus in OCA-Fibrate but not in Fibrate-OCA group. Conclusions: Triple therapy with UDCA, OCA and fibrates is able to normalise biochemical liver tests and improve pruritus in patients with difficult-to-treat PBC.
Published: 2021
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23. 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
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24. Heterogeneity of Mismatch Repair Status and Microsatellite Instability between Primary Tumour and Metastasis and Its Implications for Immunotherapy in Colorectal Cancers

Author: Camille Evrard, Stéphane Messina, David Sefrioui, Éric Frouin, Marie-Luce Auriault, Romain Chautard, Aziz Zaanan, Marion Jaffrelot, Christelle De La Fouchardière, Thomas Aparicio, Romain Coriat, Julie Godet, Christine Silvain, Violaine Randrian, Jean-Christophe Sabourin, Rosine Guimbaud, Elodie Miquelestorena-Standley, Thierry Lecomte, Valérie Moulin, Lucie Karayan-Tapon, Gaëlle Tachon, and David Tougeron
Subjects: congenital, hereditary, and neonatal diseases and abnormalities, Organic Chemistry, nutritional and metabolic diseases, General Medicine, DNA Mismatch Repair, Immunohistochemistry, digestive system diseases, Catalysis, Computer Science Applications, Inorganic Chemistry, Humans, Microsatellite Instability, Immunotherapy, colorectal cancer, microsatellite instability, deficient mismatch repair, immunohistochemistry, inter-tumoral heterogeneity, Physical and Theoretical Chemistry, Colorectal Neoplasms, neoplasms, Molecular Biology, Spectroscopy
Abstract: Deficient mismatch repair system (dMMR)/microsatellite instability (MSI) is found in about 5% of metastatic colorectal cancers (mCRCs) with a major therapeutic impact for immune checkpoint inhibitor (ICI) use. We conducted a multicentre study including all consecutive patients with a dMMR/MSI mCRC. MSI status was determined using the Pentaplex panel and expression of the four MMR proteins was evaluated by immunohistochemistry (IHC). The primary endpoint was the rate of discordance of dMMR/MSI status between primary tumours and paired metastases. We included 99 patients with a dMMR/MSI primary CRC and 117 paired metastases. Only four discrepancies (3.4%) with a dMMR/MSI primary CRC and a pMMR/MSS metastasis were initially identified and reviewed by expert pathologists and molecular biologists. Two cases were false discrepancies due to human or technical errors. One discordant case could not be confirmed due to the low level of tumour cells. The last case had a confirmed discrepancy with a dMMR/MSI primary CRC and a pMMR/MSS peritoneal metastasis. Our study demonstrated a high concordance rate of dMMR/MSI status between primary CRCs and their metastases. The analysis of one sample, either from the primary tumour or metastasis, with consistent dMMR and MSI status seems to be sufficient prior to treatment with ICI.
Published: 2022
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25. Chronic Alcohol Consumption Exacerbates the Severity of Psoriasiform Dermatitis in Mice

Author: Philippe Vasseur, Christine Silvain, Jean-Claude Lecron, Coralie Gisclard, Jean-François Jégou, Mathilde Pohin, and Franck Morel
Subjects: Keratinocytes, Chemokine, Interferon Inducers, Exacerbation, Alcohol Drinking, 030508 substance abuse, Medicine (miscellaneous), Inflammation, Imiquimod, Toxicology, Interleukin-23, 03 medical and health sciences, Mice, 0302 clinical medicine, Psoriasis, medicine, Animals, Psoriasiform Dermatitis, Skin, Chemokine CCL20, integumentary system, biology, Ethanol, business.industry, Gene Expression Profiling, Interleukins, Interleukin-17, Central Nervous System Depressants, medicine.disease, CCL20, Psychiatry and Mental health, Immunology, biology.protein, Th17 Cells, medicine.symptom, 0305 other medical science, business, 030217 neurology & neurosurgery, Epidermal thickening, medicine.drug
Abstract: Background A relationship between alcohol consumption and psoriasis has been reported, but it is unclear whether alcohol consumption aggravates psoriasis. Here, we studied the effect of chronic ethanol (EtOH) consumption in the murine model of Aldara-induced psoriasiform dermatitis. Methods C57BL/6 mice received 5% EtOH in their drinking water for 10 weeks. Dermatitis was induced from weeks 9 to 10, by applying Aldara to the shaved patch of skin on the back. Inflammation was characterized by histological and transcriptomic analyses. Results EtOH consumption aggravated Aldara-induced dermatitis. The scales were more severe, epidermal thickening was more pronounced, and cutaneous expression of Th17-related cytokines was exacerbated. Control mice simply receiving EtOH displayed minimal cutaneous inflammation, characterized by epidermal infiltrates of T lymphocytes and the overexpression of IL-17A and the Th17-recruiting chemokine CCL20. In vitro studies showed that low concentrations of EtOH induce the expression of CCL20 by murine epidermal keratinocytes. Conclusion Alcohol consumption leads to subliminar skin inflammation, which is revealed by the exacerbation of Aldara-induced experimental psoriasiform dermatitis, likely through Th17-type minimal skin inflammation. These results favor the systematic management of alcohol consumption in psoriatic patients.
Published: 2020

26. Diagnostic Accuracy of a Noninvasive Test for Detection of Helicobacter pylori and Resistance to Clarithromycin in Stool by the Amplidiag H. pylori+ClariR Real-Time PCR Assay

Author: Lauranne Broutin, Christophe Burucoa, Anaïs de Singly, Quentin Thiebault, Maxime Pichon, Clémence Lefèvre, Benoit Pichard, Vincent Croquet, Christine Silvain, Thierry Barrioz, Ginette Fotsing, Chloé Plouzeau, Julie Cremniter, Anthony Michaud, Vuillemin E, Alexandre Chéron, Paul-Arthur Haineaux, Philippe Vasseur, Marc Wangermez, Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers), and PICHON, Maxime
Subjects: 0301 basic medicine, diagnosis, Biopsy, Gastroenterology, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Clarithromycin, Positive predicative value, Medicine, Prospective Studies, stool, Antrum, Finland, biology, Anti-Bacterial Agents, PCR, Real-time polymerase chain reaction, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030211 gastroenterology & hepatology, medicine.drug, Adult, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, noninvasive sampling, Microbial Sensitivity Tests, Real-Time Polymerase Chain Reaction, Helicobacter Infections, 03 medical and health sciences, Internal medicine, molecular diagnosis, Drug Resistance, Bacterial, Humans, gastric ulcers, Etest, Helicobacter pylori, business.industry, gastric cancer, Bacteriology, Histology, bacterial infections and mycoses, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Confidence interval, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business
Abstract: International audience; The noninvasive detection of Helicobacter pylori and its resistance to clarithromycin could revolutionize the management of H. pylori-infected patients by tailoring eradication treatment without any need for endoscopy when histology is not necessary. Several real-time PCR tests performed on stools have been proposed, but their performances were either poor or they were tested on too few patients to be properly evaluated. We conducted a prospective, multicenter study including 1,200 adult patients who were addressed for gastroduodenal endoscopy with gastric biopsies and who were naive for eradication treatment in order to evaluate the performance of the Amplidiag H. pyloriϩClariR assay recently developed by Mobidiag (Espoo, Finland). The results of the Amplidiag H. pyloriϩClariR assay performed on DNA from stools (automatic extraction with the EasyMag system [bioMérieux]) were compared with those of culture/Etest and quadruplex real-time PCRs performed on two gastric biopsy samples (from the antrum and corpus) to detect the H. pylori glmM gene and mutations in the 23S rRNA genes conferring clarithromycin resistance. The sensitivity and specificity of the detection of H. pylori were 96.3% (95% confidence interval [CI], 92 to 98%) and 98.7% (95% CI, 97 to 99%), respectively. The positive and negative predictive values were evaluated to be 92.2% (95% CI, 92 to 98%) and 99.3% (95% CI, 98 to 99%), respectively. In this cohort, 160 patients (14.7%) were found to be infected (positive by culture and/or PCR). The sensitivity and specificity for detecting resistance to clarithromycin were 100% (95% CI, 88 to 100%) and 98.4% (95% CI, 94 to 99%), respectively.
Published: 2020
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27. Hereditary hemorrhagic telangiectasia and liver involvement: Vascular liver diseases: position papers from the francophone network for vascular liver diseases, the French Association for the Study of the Liver (AFEF), and ERN-rare liver

Author: Christine, Silvain, Thierry, Thévenot, Isabelle, Colle, Valérie, Vilgrain, Sophie, Dupuis-Girod, Elisabetta, Buscarini, Dominique, Valla, Sophie, Hillaire, Danielle, Dutheil, Olivier, Sitbon, Christophe, Bureau, and Aurélie, Plessier
Subjects: Liver, Liver Diseases, Humans, Telangiectasia, Hereditary Hemorrhagic, Vascular Diseases
Published: 2020

28. 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
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29. 12 Weeks of a Ribavirin‐Free Sofosbuvir and Nonstructural Protein 5A Inhibitor Regimen Is Enough to Treat Recurrence of Hepatitis C After Liver Transplantation

Author: Audrey Coilly, Carole Cagnot, Pascal Lebray, Stéphane Chevaliez, Alpha Diallo, Victor de Lédinghen, Jean-Charles Duclos-Vallée, Danielle Botta-Fridlund, Claire Francoz, Camille Besch, Nassim Kamar, Christine Silvain, P. Perré, Albert Tran, Jérôme Dumortier, François Habersetzer, Claire Fougerou-Leurent, Aurelie Veislinger, Valérie Canva, Vincent Di Martino, Georges-Philippe Pageaux, Filomena Conti, Caroline Jezequel, Christophe Duvoux, Armando Abergel, Christophe Moreno, Sylvie Radenne, Maryline Debette-Gratien, H. Montialoux, Emilie Rossignol, Vincent Leroy, Louis d’Alteroche, and Pauline Houssel-Debry
Subjects: Liver Cirrhosis, Male, Sofosbuvir, medicine.medical_treatment, Viral Nonstructural Proteins, 030230 surgery, Liver transplantation, medicine.disease_cause, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Belgium, Recurrence, Prospective Studies, 10. No inequality, education.field_of_study, Graft Survival, virus diseases, Hepatitis C, Middle Aged, Sciences bio-médicales et agricoles, Prognosis, 3. Good health, Treatment Outcome, Disease Progression, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, France, Viral load, medicine.drug, Adult, medicine.medical_specialty, Hepatitis C virus, Population, Drug Administration Schedule, 03 medical and health sciences, Internal medicine, Ribavirin, medicine, Humans, education, Aged, Dose-Response Relationship, Drug, Hepatology, business.industry, Hepatitis C, Chronic, medicine.disease, digestive system diseases, Liver Transplantation, Regimen, chemistry, business
Abstract: Sofosbuvir (SOF) combined with nonstructural protein 5A (NS5A) inhibitors has demonstrated its efficacy in treating a recurrence of hepatitis C virus (HCV) after liver transplantation (LT). However, the duration of treatment and need for ribavirin (RBV) remain unclear in this population. Our aim was to determine whether LT recipients could be treated with an SOF + NS5A inhibitor-based regimen without RBV for 12 weeks post-LT. Between October 2013 and December 2015, 699 LT recipients experiencing an HCV recurrence were enrolled in the multicenter ANRS CO23 CUPILT cohort. We selected patients receiving SOF and NS5A inhibitor ± RBV and followed for at least 12 weeks after treatment discontinuation. The primary efficacy endpoint was a sustained virological response 12 weeks after the end of treatment (SVR12). Among these 699 patients, 512 fulfilled the inclusion criteria. Their main characteristics were: 70.1% genotype 1, 18.2% genotype 3, 21.1% cirrhosis, and 34.4% previously treated patients. We identified four groups of patients according to their treatment and duration: SOF + NS5A without RBV for 12 (156 patients) or 24 (239 patients) weeks; SOF + NS5A + RBV for 12 (47 patients) or 24 (70 patients) weeks. SVR12 values reached 94.9%, 97.9%, 95.7%, and 92.9%, respectively (P = 0.14). Only 20 patients experienced a treatment failure. Under multivariate analysis, factors such as fibrosis stage, previous treatment, HCV genotype, and baseline HCV viral load did not influence SVR12 rates in the four groups (P = 0.21). Hematological adverse events (AEs) were more common in the RBV group: anemia (P < 0.0001) and blood transfusion (P = 0.0001). Conclusion: SOF + NS5A inhibitors without RBV for 12 weeks constituted reliable therapy for recurrent HCV post-LT with an excellent SVR12 whatever the fibrosis stage, HCV genotype, and previous HCV treatment. (Hepatology 2018; 00:000-000)., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2018
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30. 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
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31. Recipient Selection for Optimal Utilization of Discarded Grafts in Liver Transplantation

Author: Frédéric Marques, Martine Ferrandière, Anne-Charlotte Tellier, Giovanni Giretti, Ephrem Salamé, Maryline Debette-Gratien, Mario Altieri, Christine Silvain, Jean-Marc Perarnau, Xavier Causse, Petru Bucur, Vincent Kerouredan, and Louise Barbier
Subjects: Transplantation, medicine.medical_specialty, Framingham Risk Score, Donor selection, business.industry, medicine.medical_treatment, Context (language use), Retrospective cohort study, 030230 surgery, Liver transplantation, medicine.disease, Surgery, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Hepatocellular carcinoma, medicine, 030211 gastroenterology & hepatology, Graft survival, business
Abstract: BACKGROUND In France, liver grafts that have been refused by at least 5 teams are considered for rescue allocation (RA), with the choice of the recipient being at the team's discretion. Although this system permits the use of otherwise discarded grafts in a context of organ shortage, outcomes and potential benefits need to be assessed. METHODS Between 2011 and 2015, outcomes of RA grafts (n = 33) were compared with SA grafts (n = 321) at a single French center. RESULTS Liver grafts in the RA group were older (63 ± 17 years vs 54 ± 18 years, P = 0.007) and had a higher DRI (1.86 ± 0.45 vs 1.61 ± 0.47, P = 0.010). Recipients in this group had a lower Model for End-Stage Liver Disease score (14 ± 5 vs 22 ± 10, P < 0.001) and had mostly hepatocellular carcinoma (67.0% vs 40.4%, P = 0.010). The balance of risk score was significantly lower in the RA group (5.5 ± 2.9 vs 9.2 ± 5.5, P < 0.001). There were higher rates of early and delayed hepatic artery thrombosis (15.2% vs 3.1%, P = 0.001) and retransplantation (18.2% vs 4.7%, P = 0.002) in the RA group. Patient survival was not different between groups, but graft survival was impaired (95% vs 82% at 1 year and 94% vs 74% at 3 years, P = 0.001). CONCLUSION Our results show that discarded liver grafts can be used provided that there is a strict recipient selection process, although hepatic artery thrombosis and retransplantation are more frequent. This strategy enables utilization of otherwise discarded grafts in the context of organ shortage.
Published: 2018
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32. Liver fibrosis is associated with cutaneous inflammation in the imiquimod-induced murine model of psoriasiform dermatitis

Author: N. Venisse, Jiad N. Mcheik, Philippe Vasseur, Christine Silvain, Laure Favot, Jean-Claude Lecron, Mathilde Pohin, Jean-François Jégou, Franck Morel, Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre hospitalier universitaire de Poitiers (CHU Poitiers)
Subjects: Liver Cirrhosis, Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Interferon Inducers, education, Imiquimod, macromolecular substances, Dermatology, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, 030207 dermatology & venereal diseases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Fibrosis, Psoriasis, medicine, Animals, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Psoriasiform Dermatitis, Sirius Red, ComputingMilieux_MISCELLANEOUS, health care economics and organizations, Hepatitis, Liver injury, integumentary system, business.industry, medicine.disease, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 3. Good health, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, chemistry, Immunology, Hepatic stellate cell, Drug Eruptions, Chemical and Drug Induced Liver Injury, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, medicine.drug
Abstract: SummaryBackground Psoriasis associates several extra-cutaneous manifestations. Little is known about hepatic parameters specifically associated with psoriasis. Objective To study whether psoriasiform dermatitis is associated with liver injury. Methods We studied liver parameters of inflammation and fibrosis in a murine model of psoriasiform dermatitis induced by topical application of imiquimod for nine weeks. Results Topical treatment with imiquimod induced a form of psoriasiform dermatitis reminiscent of the human disorder, characterized by thickened and scaly skin, psoriasiform epidermal hyperplasia, altered keratinocyte differentiation, and cutaneous overexpression of interleukin-17A. Mice with dermatitis displayed hepatitis, as shown by elevation of plasma transaminase levels, as well as portal and periportal hepatitis characterized by T lymphocyte (CD3e+) and polymorphonuclear cell (Gr1+) infiltrates. The hepatitis progressed toward liver fibrogenesis, as shown by excessive Sirius red staining, consistent with the expression of alpha-smooth muscle actin by hepatic stellate cells. Conclusions These results indicate that liver inflammation and fibrosis is associated with experimental psoriasiform dermatitis. Our results suggest that psoriatic inflammation may be associated with specific liver injury. This article is protected by copyright. All rights reserved.
Published: 2018
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33. 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
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34. Direct-acting antiviral agent–based regimen for HCV recurrence after combined liver-kidney transplantation: Results from the ANRS CO23 CUPILT study

Author: Jérôme Dumortier, A. Rohel, Jean-Charles Duclos-Vallée, Christophe Duvoux, Vincent Di Martino, Christine Silvain, Sébastien Dharancy, Danielle Botta-Fridlund, Sylvie Radenne, Maryline Debette-Gratien, Nassim Kamar, Audrey Coilly, Vincent Leroy, Georges-Philippe Pageaux, Armand Abergel, Louis d’Alteroche, Emilie Rossignol, Claire Francoz, Pauline Houssel-Debry, P. Perré, Filomena Conti, Claire Fougerou-Leurent, François Habersetzer, Camille Besch, Christophe Moreno, H. Montialoux, Valérie Canva, Albert Tran, Didier Samuel, Victor de Lédinghen, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Paul Brousse, Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Rennes] (CIC), 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 Pontchaillou [Rennes], Service d'Hépatologie, Hôpital Henri Mondor, AP-HP, Créteil, France., Hôpital Henri Mondor, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Centre méditerranéen de médecine moléculaire (C3M), 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'hépato-gastro-entérologie, Hôpital Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Département d'hépatologie, Service d'hépatologie, 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), Hôpital de la Croix-Rousse [CHU - HCL], Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Chirurgie Digestive, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), 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), Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, Chirurgie digestive et hépatobiliaire, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, ANRS France Recherche Nord & sud Sida-hiv hépatites, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Paul Brousse-Université Paris-Sud - Paris 11 (UP11), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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 Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: Graft Rejection, Male, Sofosbuvir, [SDV]Life Sciences [q-bio], medicine.medical_treatment, kidney transplantation/nephrology, Hepacivirus, 030230 surgery, Liver transplantation, medicine.disease_cause, 0302 clinical medicine, Recurrence, Risk Factors, Immunology and Allergy, liver disease: infectious, Pharmacology (medical), Prospective Studies, Prospective cohort study, education.field_of_study, Graft Survival, Middle Aged, Prognosis, Hepatitis C, 3. Good health, [SDV] Life Sciences [q-bio], kidney failure/injury, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, medicine.drug, Adult, medicine.medical_specialty, infectious disease, Hepatitis C virus, Population, clinical research/practice, Antiviral Agents, 03 medical and health sciences, Internal medicine, medicine, Humans, Adverse effect, education, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Transplantation, business.industry, Kidney Transplantation, Liver Transplantation, Regimen, Immunology, infection and infectious agents - viral: hepatitis C, business, liver transplantation/hepatology, Follow-Up Studies
Abstract: International audience; Hepatitis C virus (HCV) infection is associated with reduced patient survival following combined liver-kidney transplantation (LKT). The aim of this study was to assess the efficacy and safety of second-generation direct-acting antivirals (DAAs) in this difficult-to-treat population. The ANRS CO23 "Compassionate use of Protease Inhibitors in Viral C Liver Transplantation" (CUPILT) study is a prospective cohort including transplant recipients with recurrent HCV infection treated with DAAs. The present work focused on recipients with recurrent infection following LKT. The study population included 23 patients. All patients received at least one NS5B inhibitor (sofosbuvir) in their antiviral regimen an average of 90 months after LKT. Ninety-six percent of recipients achieved a sustained virological response (SVR) at week 12 (SVR12). In terms of tolerance, 39% of recipients presented with at least one serious adverse event. None of the patients experienced acute rejection during therapy and there were no deaths during follow-up. The glomerular filtration rate (GFR) decreased significantly from baseline to the end of therapy. However, this study did not show that the decline in GFR persisted over time or that it was directly related to DAAs. The DAA-based regimen is well tolerated with excellent results in terms of efficacy. It will become the gold standard for the treatment of recurrent HCV following LKT.
Published: 2017
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35. 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
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36. Predicting relapse in patients with severe alcohol use disorder: The role of alcohol insight and implicit alcohol associations

Author: Ghina Harika-Germaneau, Marcello Solinas, Wilfried Serra, Xavier Noël, Christine Silvain, Nicolas Langbour, Nemat Jaafari, Meira Dandaba, Armand Chatard, Centre de Recherches sur la Cognition et l'Apprentissage (CeRCA), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de neurosciences expérimentales et cliniques (LNEC), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de recherche clinique intersectorielle en psychiatrie du Centre Hospitalier Henri Laborit, Centre Hospitalier Henri Laborit (CHL), and Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Université de Poitiers
Subjects: Alcohol Drinking, [SDV]Life Sciences [q-bio], media_common.quotation_subject, Population, 030508 substance abuse, Medicine (miscellaneous), Craving, Alcohol use disorder, Toxicology, Impulsivity, Psychologie clinique, [SCCO]Cognitive science, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Toxicologie pharmaceutique, medicine, Humans, 030212 general & internal medicine, Relapse, Risk factor, education, ComputingMilieux_MISCELLANEOUS, Cognitive deficit, media_common, education.field_of_study, Implicit association, business.industry, Sciences bio-médicales et agricoles, Abstinence, medicine.disease, Psychiatry and Mental health, Clinical Psychology, Alcoholism, Anxiety, France, medicine.symptom, Alcohol, Insight, 0305 other medical science, business, Psychiatrie, Clinical psychology
Abstract: Low insight is reported as a risk factor for relapse among patients treated for alcohol use disorders. However, to date, little is known on why patients with low insight are at higher risk for relapse. In this study, we tested the hypothesis that an implicit preference for alcohol over abstinence predicts relapse in patients with low, but not high, alcohol insight. Participants consisted of 77 patients who had received treatment for severe alcohol use disorder in a hospital in France. During hospitalization, they completed a self-report measure of insight and an implicit association test to assess implicit preference for alcohol over abstinence. The primary outcome was relapse assessed one month after discharge. Control variables were gender, age, cognitive deficit, anxiety, depression, craving, and impulsivity. Data were analysed using logistic regression analysis. After adjusting for demographic and clinical variables, relapse was predicted by the interaction between insight and implicit preference for alcohol but not by their main effects alone. Implicit preference for alcohol predicted relapse among patients with relatively low insight, but not among those with relatively high insight. These findings suggest that patients with low insight and strong implicit preference for alcohol are at a higher risk of relapse. Clinicians may therefore focus on and tailor specific interventions to prevent relapse in this vulnerable and at-risk population., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2019
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37. Evaluation of hepatic iron concentration heterogeneities using the MRI R2* mapping method

Author: G. Herpe, Jean Mazé, S. Boucebci, Christine Silvain, Jean-Pierre Tasu, G. Vesselle, Pierre Ingrand, Centre hospitalier universitaire de Poitiers (CHU Poitiers), and Université de Poitiers
Subjects: Adult, Male, Iron Overload, Iron, [SDV]Life Sciences [q-bio], Standard deviation, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Fat saturation, Fitting methods, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Prospective Studies, Truncation (statistics), Patient group, medicine.diagnostic_test, business.industry, Liver segment, Magnetic resonance imaging, General Medicine, Middle Aged, Magnetic Resonance Imaging, Hepatic Iron Concentration, Liver, 030220 oncology & carcinogenesis, Female, business, Nuclear medicine
Abstract: Objective To measure hepatic iron concentration (HIC) heterogeneities using a magnetic resonance R2* mapping method. Patients and methods Ninety-four patients with suspected hepatic iron overload and 10 volunteers were included prospectively. A multi-echo R2* sequence with fat saturation and with three post-processing fitting methods (a single exponential decay model with or without truncation, SED and SEDt, and a constant offset model, COS) was compared to a signal intensity ratio method (SIR), considered as the reference. HIC heterogeneity was evaluated from R2* mapping after placing a ROI on each liver segment. Results A strong linear correlation between SIR and R2* methods using the SEDt and COS models was observed (r = 0.973 and 0.955, respectively). Volunteers and patient liver variabilities, quantified by mean intra-liver standard deviation (SD) were 1.58 μmol/g (mean range 5.06 μmol/g) and 4.73 μmol/g (mean range 19.08 μmol/g), respectively. For the patient group, the highest HIC was observed in the IVth segment. Heterogeneity increased for patients with an HIC > 60 μmol/g (mean intra-liver SD = 13.90 μmol/g; mean range = 50.60 μmol/g). Conclusion This study is the first to demonstrate in vivo HIC heterogeneities using whole-liver mapping analysis. These preliminary results require confirmation through further studies, but might be useful in cases of single ROI analysis.
Published: 2019
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38. 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
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39. Liver transarterial chemoembolization and sunitinib for unresectable hepatocellular carcinoma: Results of the PRODIGE 16 study

Author: David Sefrioui, Julien Edeline, M. Baconnier, Karine Le Malicot, Barbara Dauvois, Alexandra Heurgue, Jean-Louis Jouve, Sébastien Dharancy, Julien Vergniol, Yves Rinaldi, Hervé Perrier, Maryline Debette-Gratien, Yves Becouarn, Mohamed Hebbar, Anthony Turpin, Christine Silvain, Côme Lepage, Thierry Lecomte, Gael Deplanque, Thierry de Baere, and Isabelle Ollivier-Hourmand
Subjects: medicine.medical_specialty, Carcinoma, Hepatocellular, Neutropenia, urologic and male genital diseases, Placebo, Placebo group, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Sunitinib, medicine, Humans, Chemoembolization, Therapeutic, Hepatology, business.industry, Liver Neoplasms, Liver failure, medicine.disease, Acute toxicity, Treatment Outcome, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Dose reduction, business, Liver Failure, medicine.drug
Abstract: Summary Background Trans-arterial chemoembolization (TACE) is one first-line option therapy for patients with hepatocellular carcinoma (HCC) not suitable for surgical resection. Aims We evaluated the effects of sunitinib plus doxorubicin-TACE on bleeding or liver failure. Methods Seventy-eight patients with HCC were included in this randomized, double-blind study. They received one to three TACE plus either sunitinib or placebo four weeks out of six for one year. The occurrence of severe bleeding or liver failure was assessed during the week after the TACE. The safety and survival outcomes were evaluated. Results No bleeding complication was reported. One and two liver failures were respectively observed in sunitinib and placebo patients. Compliance to sunitinib treatment was acceptable. Sunitinib dose reduction occurred in 37% of patients due to acute toxicity. Main grade 3–4 toxicities were: thrombocytopenia, neutropenia, increased bilirubin, increased ALT and asthenia. In the sunitinib group, the median PFS and OS were 9.05 [5.81;11.63] and 25.0 [13.5;36.8] months, respectively. In the placebo group, the median PFS and OS were 5.51 [4.14;7.79] and 20.5 [15.1;30.6] months, respectively. Conclusions TACE plus sunitinib in the first-line therapy for patients with HCC not suitable for surgical resection was feasible. ClinicalTrials.gov number NCT01164202.
Published: 2021
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40. Cocaine-induced acute hepatitis: A diagnosis not to forget

Author: Matthieu Lesbordes, Marie-Christine Perault-Pochat, Bernard Fauconneau, Emilie Bouquet, Eric Frouin, Christine Silvain, and Stéphanie Pain
Subjects: medicine.medical_specialty, Hepatology, business.industry, Internal medicine, Addiction, media_common.quotation_subject, Gastroenterology, MEDLINE, Medicine, business, Acute hepatitis, media_common
Published: 2021
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41. High-Fat Diet–Induced IL-17A Exacerbates Psoriasiform Dermatitis in a Mouse Model of Steatohepatitis

Author: Mathilde Pohin, Isabelle Petit-Paris, Jean-Claude Lecron, Hans Yssel, Michel Samson, Laure Favot, Christine Silvain, Franck Morel, Adriana Delwail, Jean-François Jégou, Pierre Levillain, Philippe Vasseur, Laura Serres, Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, Signalisation et Transports Ioniques Membranaires (STIM), Université de Tours-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Anatomo-Pathologie, CHU de Poiters, Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Centre d'Immunologie et de Maladies Infectieuses (CIMI), 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), Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), University of Poitiers, Poitiers University Hospital, Nord Deux-Sevres Hospital, Region Poitou-Charentes, Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-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 ), and 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)
Subjects: Male, 0301 basic medicine, Pathology, medicine.medical_specialty, mice, Erythema, Fluorescent Antibody Technique, Dermatitis, Acanthosis, Diet, High-Fat, Real-Time Polymerase Chain Reaction, Pathology and Forensic Medicine, 030207 dermatology & venereal diseases, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, skin inflammation, Psoriasis, Nonalcoholic fatty liver disease, medicine, Animals, Psoriasiform Dermatitis, risk, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, innate lymphoid-cells, business.industry, Interleukin-17, il-22, Fatty liver, Flow Cytometry, medicine.disease, cytokines, 3. Good health, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Immunology, liver-disease, Steatohepatitis, medicine.symptom, business
Abstract: International audience; Recent studies suggest that psoriasis may be more severe in patients with nonalcoholic fatty liver disease, particularly in those with the inflammatory stage of steatohepatitis [nonalcoholic steatohepatitis (NASH)]. Herein, we investigated the impact of diet-induced steatohepatitis on the severity of imiquimod-induced psoriasiform dermatitis. Mice fed with a high-fat diet developed steatohepatitis reminiscent of human NASH with ballooning hepatocytes and significant liver fibrosis. Mice with steatohepatitis also displayed moderate cutaneous inflammation characterized by erythema, dermalinfiltrates of CD45(+) leukocytes, and a local production of IL-17A. Moreover, steatohepatitis was associated with an epidermal activation of caspase-1 and cutaneous overexpression of IL-1 beta. Imiquimod-induced psoriasiform dermatitis was exacerbated in mice with steatohepatitis as compared to animals fed with a standard diet. Scale formation and acanthosis were aggravated, in correlation with increased IL-17A and IL-22 expression in inflamed skins. Finally, intradermal injection of IL-17A in standard diet-fed mice recapitulated the cutaneous pathology of mice with steatohepatitis. The results show that high-fat diet induced steatohepatitis aggravates the inflammation in psoriasiform dermatitis, via the cutaneous production of IL-17A. In agreement with clinical data, this description of a novel extrahepatic manifestation of NASH should sensitize dermatologists to the screening and the management of fatty liver in psoriatic patients.
Published: 2016
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42. 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
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43. 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
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44. Safety of sofosbuvir-based regimens after liver transplantation longitudinal assessment of renal function in the prospective ANRS CO23 CUPILT study

Author: Rodolphe Anty, Alpha Diallo, Vincent Leroy, L. D’Alteroche, Jean Charles Duclos-Vallée, Claire Fougerou-Leurent, Christophe Duvoux, Vincent L.M. Esnault, P. Perré, François Habersetzer, Audrey Coilly, Aurelie Veislinger, Nassim Kamar, V. Di Martino, Emilie Rossignol, Valérie Canva, Maryline Debette-Gratien, Carole Cagnot, François Durand, Didier Samuel, Clémence M. Canivet, Danielle Botta-Fridlund, H. Montialoux, V. de Ledinghen, Christine Silvain, Camille Besch, Jérôme Dumortier, Albert Tran, Guillaume Favre, Pauline Houssel-Debry, Georges Philippe Pageaux, S. Radenne, H. Danjou, Sébastien Dharancy, Fabio Conti, Pascal Lebray, Armando Abergel, Christophe Moreno, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre méditerranéen de médecine moléculaire (C3M), 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)-Université Côte d'Azur (UCA), Laboratoire de PhysioMédecine Moléculaire (LP2M), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), 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), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Grenoble, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Toulouse [Toulouse], Hôpital Claude Huriez [Lille], CHU Lille, Hôpital Edouard Herriot [CHU - HCL], 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), CHU Strasbourg, CHU Marseille, CHU Rouen, Normandie Université (NU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, CHU Limoges, ANRS France Recherche Nord & sud Sida-hiv hépatites, Hôpital Lapeyronie [Montpellier] (CHU), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: medicine.medical_specialty, Sofosbuvir, Hepatitis C virus, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Urology, Renal function, Hepacivirus, 030230 surgery, Liver transplantation, medicine.disease_cause, Kidney, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Recurrence, Ribavirin, Medicine, Humans, Pharmacology (medical), Longitudinal Studies, Prospective Studies, Renal Insufficiency, Chronic, Aged, Creatinine, Hepatology, business.industry, Gastroenterology, Middle Aged, Hepatitis C, 3. Good health, Liver Transplantation, medicine.anatomical_structure, chemistry, Cohort, 030211 gastroenterology & hepatology, Female, business, medicine.drug, Glomerular Filtration Rate
Abstract: International audience; Background In liver transplant recipients with hepatitis C virus recurrence, there is concern about renal safety of sofosbuvir-based regimens. Changes in serum creatinine or in the estimated glomerular filtration rate (eGFR) under treatment are used to look for possible renal toxicity. However, serum creatinine and eGFR are highly variable. Aim To analyse renal function trajectory with numerous assays of serum creatinine over a long period of time. Methods In a multicentre cohort of 139 patients, the eGFR was obtained from serum creatinine using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Slopes of eGFR were defined as a change in eGFR during a period divided by time. Pre-treatment, on-treatment and post-treatment periods were 9 months, 3-9 months and 4.5 months. Interactions between eGFR slopes and the pre-treatment eGFR, use of ribavirin or mycophenolate mofetil, and stage of fibrosis were addressed. On-treatment eGFR slopes were separated in tertiles. Pre- and post-treatment eGFR slopes were compared globally and according to tertiles. Results The post-treatment eGFR slope was significantly better than pre-treatment eGFR slope (+0.18 (IQR -0.76 to +1.32) vs -0.11 (IQR -1.01 to +0.73) mL/min/1.73 m(2)/month, P=0.03) independently of the pre-treatment eGFR (P=0.99), ribavirin administration (P=0.26), mycophenolate mofetil administration (P=0.51) and stage of fibrosis (F3 and F4 vs lower stages, P=0.18; F4 vs lower stages, P=0.08; F4 Child-Pugh B and C vs lower stages, P=0.38). Tertiles of on-treatment eGFR slopes were -1.71 (IQR -2.54 to -1.48), -0.78 (IQR -1.03 to -0.36) and +0.75 (IQR +0.28 to +1.47) mL/min/1.73 m(2)/month. Pre- and post-treatment eGFR slopes were not significantly different according to tertiles (respectively, P=0.34, 0.08, 0.73). Conclusion The eGFR varies during treatment and gives a confusing picture of the renal safety of sofosbuvir-based regimens. In contrast, longitudinal assessment of the eGFR shows a rising trajectory over longer time, meaning that these therapies are safe for the kidneys in our cohort of liver transplant recipients.
Published: 2018
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45. Prognosis of ALF of unknown cause: results of the French multicentre prospective HASIPRO study

Author: Christophe Duvoux, Sébastien Dharancy, Camille Besch, Philippe Ichai, Hélène Agostini, Teresa Antonini, Laurent Alric, F. Artru, Claire Francoz, Celine Piedvache, Guillaume Lassailly, Jérôme Dumortier, Vincent Leroy, Vincent Di Martino, Audrey Coilly, Jean Charles Duclos-Vallée, A.V. Pichard, Marika Rudler, Christine Silvain, Nicolas Carbonell, J. Perarnaud, Didier Samuel, S. Radenne, Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, Physiopathogénèse et Traitement des Maladies du Foie, Hôpital Paul Brousse-Université Paris-Saclay, inserm (inserm ), Hepatinov (DHU), Université Paris-Sud - Paris 11 (UP11)-Centre Hépato-Biliaire Paul Brousse, Hôpital Claude Huriez [Lille], CHU Lille, Service d'Hépatologie, Hôpital Henri Mondor, AP-HP, Créteil, France., Hôpital Henri Mondor, Service de biochimie médicale [CHRU Besançon, hôpital Minjoz], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hospices Civils de Lyon (HCL), Hôpital de la Croix-Rousse [CHU - HCL], 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), Université de Strasbourg (UNISTRA), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU de Grenoble, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Physiopathogenèse et Traitement des Maladies du Foie [Villejuif], Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 de biochimie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), and 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)
Subjects: 0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, Hepatology, HASIPRO, digestive, oral, and skin physiology, ALF, unknown, 030211 gastroenterology & hepatology, prognosis, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 3. Good health, 030304 developmental biology
Abstract: International audience; Acute liver failure (ALF) of unknown causerepresents between 10% to 50% of ALF, worldwide. Their prognosis ispoorercompared tothosewhen acause is identified. To date,no studyhas specifically focused on the prognosis of these patients. The mainobjective was to determine the factors associated with livertransplantation (LT)-free survival at 3 months.
Published: 2018
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46. Th-17 response and antimicrobial peptide expression are uniformly expressed in gastric mucosa of Helicobacter pylori -infected patients independently of their clinical outcomes

Author: Franck Morel, Christophe Burucoa, Charles Bodet, Jean-Claude Lecron, Joelle Guilhot, David Tougeron, Jean-François Jégou, Xavier Dray, Christine Silvain, Julie Cremniter, Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, ASTRE [Cergy-Pontoise], Equipes Traitement de l'Information et Systèmes (ETIS - UMR 8051), CY Cergy Paris Université (CY)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de l'Electronique et de ses Applications (ENSEA)-CY Cergy Paris Université (CY)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de l'Electronique et de ses Applications (ENSEA), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), and Laboratoire de Bactériologie, CHU de Poitiers
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_treatment, Antimicrobial peptides, Virulence, Inflammation, Helicobacter Infections, Young Adult, 03 medical and health sciences, Bacterial Proteins, Gastric mucosa, medicine, Humans, CagA, Prospective Studies, Aged, Aged, 80 and over, Antigens, Bacterial, Helicobacter pylori, biology, business.industry, Gastroenterology, General Medicine, Middle Aged, biology.organism_classification, bacterial infections and mycoses, digestive system diseases, 3. Good health, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, Cytokine, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Gastric Mucosa, Gastritis, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Inflammation Mediators, medicine.symptom, business, Antimicrobial Cationic Peptides
Abstract: Background The pathological determinism of H. pylori infection is explained by complex interplay between bacterial virulence and host inflammatory response. In a large prospective multicenter clinical study, Th17 response, expression of antimicrobial peptides (AMPs), cagA and vacA status, and bacterial density were investigated in the gastric mucosa of H. pylori -infected patients. Materials and methods Gastric inflammatory response was analyzed by RT-qPCR for quantification of Th17 cytokines (IL-17A, IL-22), CXCL-8, and AMPs (BD2 and S100A9) mRNA levels in gastric biopsies. Detection and genotyping of H. pylori strains were achieved by bacterial culture and PCR. Results Among 787 patients screened for H. pylori, 269 were analyzed (147 H. pylori -infected and 122 uninfected patients). In H. pylori -infected patients, distribution was 83 gastritis, 12 duodenal ulcers, 5 gastric ulcers, and 47 precancerous and cancerous lesions. CXCL-8, IL-17A, BD2, and S100A9 mRNA levels were significantly increased in H. pylori -infected patients but, surprisingly, IL-22 was not, and no difference was shown between H. pylori -related diseases. A positive correlation was identified between S100A9 expression and bacterial density. Although expression of the virulence genes cagA and vacA did not impact inflammatory response, patients infected with a cagA-positive strain were associated with severe H. pylori -related diseases. Conclusion This study showed that CXCL-8, IL-17A, and AMPs are not differently expressed according to the various H. pylori -related diseases. The clinical outcome determinism of H. pylori infection is most likely not driven by gastric inflammation but rather tends to mainly influenced by bacterial virulence factors.
Published: 2018
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47. Severe liver failure rather than cirrhosis is associated with mortality in patients with infectious endocarditis: a retrospective case-control study

Author: Christophe Bureau, Je Combining Acute Accent Rôme Dumortier, Anis Sfaxi, Manon Allaire, Laurent Spahr, Jacques Denis, Vincent Di Martino, Gilles Macaigne, Jean-Pierre Bronowicki, Jean-Didier Grangé, Vincent Jouannaud, Salah Zerkly, Teresa Antonini, Isabelle Ollivier-Hourmand, Alexandre Pariente, Alexandre Louvet, He Combining Acute Accent le Combining Grave Accent Ne Blasco-Perrin, Pierre Iaria, Karine Dupont, Jean-Baptiste Nousbaum, Carine Chagneau-Derrode, Agne Combining Grave Accent S Pe Combining Acute Accent Laquier, Patrice Cacoub, Thierry Thevenot, Je Combining Acute Accent Rome Gournay, Jean-François Cadranel, Thong Dao, Ryme Chentouh, Christine Silvain, Isabelle Rosa-He Combining Acute Accent Zode, Nathalie Ganne-Carrie Combining Acute Accent, Xavier Causse, Marc Bourlie Combining Grave Accent Re, Laurent Alric, Armand Garioud, Hortensia Lison, Pagès, Nathalie, 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), Lab Excellence Inflamex (CRI INSERM U1149 - Bichat Medical Faculty), Université Paris Diderot - Paris 7 (UPD7), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre hospitalier de Pau, Centre Hospitalier de Montélimar, CH Montélimar, Centre Hospitalier Universitaire Marseille, CHU Marseille, Centre Hospitalier Régional d'Orléans (CHRO), CHU Brest - Service hépato-gastro-entérologie (CHU de Brest) (CHU Brest - Service hépato-gastro-entérologie), CHU Lyon Croix-Rousse, Hospices civils de Lyon, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Intercommunal de Créteil (CHIC), Centre hospitalier universitaire de Bondy, CHU Bondy, Service de Cardiologie, Centre Hospitalier Lagny-Marne la Vallée, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de chirurgie digestive et viscérale [Corbeil-Essonnes], Centre Hospitalier Sud Francilien, CH Evry-Corbeil-CH Evry-Corbeil, and Group Hospitalier public Sud Oise GHPSO (Creil)
Subjects: Liver Cirrhosis, Male, Cirrhosis, [SDV]Life Sciences [q-bio], Severity of Illness Index, Bacterial / drug therapy, 0302 clinical medicine, Risk Factors, Liver Cirrhosis / complications, Hospital Mortality, Liver Failure / mortality, Heart Diseases / epidemiology, Endocarditis, Gastroenterology, Bacterial / mortality, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Liver Failure / physiopathology, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, France, Switzerland, medicine.medical_specialty, Heart Diseases, MEDLINE, Switzerland / epidemiology, 03 medical and health sciences, France / epidemiology, Internal medicine, Severity of illness, medicine, Humans, In patient, Cardiac Surgical Procedures, Aged, Retrospective Studies, Hepatology, business.industry, Case-control study, Liver failure, Retrospective cohort study, Endocarditis, Bacterial, medicine.disease, Bacterial / complications, Liver Cirrhosis / mortality, Case-Control Studies, business, Liver Failure
Abstract: International audience; Background: Data on infectious endocarditis (IE) in patients with liver cirrhosis (LC) are sparse. We aimed to describe the characteristics and predictors of mortality from IE in patients with LC.Patients and methods: Overall, 101 patients with LC and 101 controls with IE matched for sex, age, date of IE, and diabetes were retrospectively selected in 23 liver units between 2000 and 2013.Results: Mean age was 60.8±10.5 and 60.6±11.5 years in LC and controls, respectively. Causes of cirrhosis (Child-Pugh A/B/C: 10.4%/41.7%/47.9%, MELD score: 17±7.8) were excess alcohol intake (79.6%), viral hepatitis (17.3%), and metabolic syndrome (14.3%). Previous history of cardiopathy was found in 24.8% of LC (prosthetic valve 8.9%) and 37.6% of controls (P=0.07). The most frequent bacteria involved were gram-positive cocci. LC had significantly fewer aminoglycosides (P=0.0007), rifamycin (P=0.03), and valve surgery (P=0.02) than controls. The proportion of patients who died following cardiac surgery was similar between the two groups (9.7% for LC vs. 8.7% for controls, P=1). In-hospital mortality for Child-Pugh C patients was significantly higher than controls (61.4 vs. 23%, P
Published: 2018

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

Author: Jean-Pierre Zarski, Raoul Poupon, Christine Silvain, Victor de Ledinghen, Dominique Rainteau, Sylvie Chollet-Martin, Fabien Zoulim, Odile Goria, Armand Abergel, Gisèle N'Kontchou, Pascal Potier, François Habersetzer, Guillaume Lefèvre, Anne Minello, Farid Gaouar, Olivier Roux, Eric Nguyen-Khac, Olivier Chazouillères, Jérôme Boursier, Lydie Humbert, Jean-Pierre Bronowicki, Isabelle Ollivier-Hourmand, Sara Lemoinne, Maryline Debette-Gratien, Dominique Larrey, Christophe Corpechot, Luc de Chaisemartin, Philippe Mathurin, Alexandra Rousseau, Alexandra Heurgué-Berlot, Farid-Hakeem Admane, Tabassome Simon, Antonia Le Gruyer, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Référence des Maladies Rares - Maladies Inflammatoires des Voies Biliaires et Service d’Hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche Clinique de l’Est Parisien [CHU Saint-Antoine] (URC-EST), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire [Rennes], Hôpital Claude Huriez [Lille], CHU Lille, CHU Rouen, Normandie Université (NU), Service d'hépato-gastro-entérologie et oncologie digestive [CHR Orléans], Centre Hospitalier Régional d'Orléans (CHRO), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nancy (CHU Nancy), Service d’Hépato-Gastroentérologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Service d'hépato-gastro-entérologie [CHU Haut-Lévêque], Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Hôpital Robert Debré, Service d'Hépato-gastroentérologie, 51092 Reims, France, affiliation inconnue, Service d'Hépato-gastroentérologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'hépato-gastroentérologie [CHU Grenoble Alpes], Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Sud - Paris 11 (UP11), Laboratoire des biomolécules (LBM UMR 7203), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Immunologie 'Autoimmunité et Hypersensibilités' [AP-HP Hôpital Bichat, Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], and Sorbonne Université (SU)
Subjects: Liver Cirrhosis, Male, Cirrhosis, Cholangitis, Biliary/complications/drug therapy, Obeticholic Acid, Placebo-controlled study, Gastroenterology, Placebos, chemistry.chemical_compound, Liver disease, 0302 clinical medicine, Treatment Failure, Bezafibrate/adverse effects/*therapeutic use, Multicenter, Hypolipidemic Agents/adverse effects/*therapeutic use, Hypolipidemic Agents, Combination Therapy, medicine.diagnostic_test, Liver Cirrhosis, Biliary, Ursodeoxycholic Acid, Obeticholic acid, General Medicine, Middle Aged, Prognosis, Ursodeoxycholic acid, 3. Good health, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, medicine.drug, Adult, medicine.medical_specialty, Outcomes, Placebo, Biochemical Response, Bile Acids and Salts, 03 medical and health sciences, Double-Blind Method, Internal medicine, medicine, Cholangitis/*drug therapy/etiology, Humans, Placebos/therapeutic use, Prothrombin time, Bezafibrate, business.industry, Ursodeoxycholic Acid/therapeutic use, medicine.disease, Renal-Function, Bile Acids and Salts/blood, chemistry, Fenofibrate Therapy, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: IF 79.258 (2017); International audience; Background : Patients with primary biliary cholangitis who have an inadequate response to therapy with ursodeoxycholic acid are at high risk for disease progression. Fibrates, which are agonists of peroxisome proliferator–activated receptors, in combination with ursodeoxycholic acid, have shown potential benefit in patients with this condition.Methods : In this 24-month, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 100 patients who had had an inadequate response to ursodeoxycholic acid according to the Paris 2 criteria to receive bezafibrate at a daily dose of 400 mg (50 patients), or placebo (50 patients), in addition to continued treatment with ursodeoxycholic acid. The primary outcome was a complete biochemical response, which was defined as normal levels of total bilirubin, alkaline phosphatase, aminotransferases, and albumin, as well as a normal prothrombin index (a derived measure of prothrombin time), at 24 months.Results : The primary outcome occurred in 31% of the patients assigned to bezafibrate and in 0% assigned to placebo (difference, 31 percentage points; 95% confidence interval, 10 to 50; P
Published: 2018
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49. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial

Author: Valérie Vilgrain, Helena Pereira, Eric Assenat, Boris Guiu, Alina Diana Ilonca, Georges-Philippe Pageaux, Annie Sibert, Mohamed Bouattour, Rachida Lebtahi, Wassim Allaham, Hélène Barraud, Valérie Laurent, Elodie Mathias, Jean-Pierre Bronowicki, Jean-Pierre Tasu, Rémy Perdrisot, Christine Silvain, René Gerolami, Olivier Mundler, Jean-Francois Seitz, Vincent Vidal, Christophe Aubé, Frédéric Oberti, Olivier Couturier, Isabelle Brenot-Rossi, Jean-Luc Raoul, Anthony Sarran, Charlotte Costentin, Emmanuel Itti, Alain Luciani, René Adam, Maïté Lewin, Didier Samuel, Maxime Ronot, Aurelia Dinut, Laurent Castera, Gilles Chatellier, Elisabeth Delhom - Christol, Alina D Ilonca, Julie Lonjon, Mohamed Abdel-Rehim, Arnaud Dieudonné, Christophe Bazin, Carine Chagneau-Derrode, Patrick Borentain, Antoine Bouvier, Laurent Vervueren, Julia Chalaye, Hicham Kobeiter, Julien Edeline, Etienne Garin, Yan Rolland, Isabelle Archambeaud, Thomas Eugene, Eric Frampas, Christophe Cassinotto, Martine Guyot, Jean-Baptiste Hiriart, Bruno Lapuyade, Julien Vergniol, Philippe Bachellier, Julien Detour, Bernard Duclos, Michel Greget, Francois Habersetzer, Alessio Imperiale, Philippe Merle, Agnès Rode, Julie Morvan, Eric Nguyen-Khac, Thierry Yzet, Guillaume Baudin, Patrick Chevallier, Abakar Mahamat, Thierry Piche, Micheline Razzouk, Patrick Hillon, Romaric Loffroy, Michel Toubeau, Julie Vincent, Gabriele Barabino, Nadia Bouarioua, Muriel Cuilleron, Marie Ecochard, Nathalie Prevot-Bitot, Vincent Leroy, Julie Roux, Christian Sengel, Valérie Bourcier, Nathalie Ganne-Carrie, Olivier Seror, Sylvie Costo, Thông Dao, Jean-Pierre Pelage, Jérôme Dumortier, Francesco Giammarile, Pierre-Jean Valette, Nadia Ghazzar, Olivier Pellerin, Julien Taieb, Pierre Weinmann, Alexandra Heurgue-Berlot, Claude Marcus, Daniele Sommacale, Maria-Angéla Castilla-Lièvre, Sophie Maitre, Lysiane Marthey, Hôpital Beaujon, Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), 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), CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Eloi, Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), 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 Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and 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)
Subjects: Male, medicine.medical_treatment, Brachytherapy, Administration, Oral, Kaplan-Meier Estimate, Liver transplantation, Gastroenterology, 0302 clinical medicine, Yttrium Radioisotopes, MESH: Carcinoma, Hepatocellular/drug therapy, education.field_of_study, Liver Neoplasms, Radiotherapy Dosage, MESH: Carcinoma, Hepatocellular/radiotherapy, Middle Aged, Sorafenib, Microspheres, MESH: Niacinamide/analogs & derivatives, 3. Good health, MESH: Liver Neoplasms/drug therapy, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Female, 030211 gastroenterology & hepatology, MESH: Phenylurea Compounds/administration & dosage, Liver cancer, medicine.drug, Adult, Niacinamide, medicine.medical_specialty, Carcinoma, Hepatocellular, Population, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, Drug Administration Schedule, 03 medical and health sciences, Internal medicine, medicine, Carcinoma, Humans, Neoplasm Invasiveness, education, Aged, Neoplasm Staging, Dose-Response Relationship, Drug, Performance status, business.industry, Phenylurea Compounds, medicine.disease, Survival Analysis, Surgery, MESH: Yttrium Radioisotopes/therapeutic use, Liver function, business, Follow-Up Studies
Abstract: Summary Background Sorafenib is the recommended treatment for patients with advanced hepatocellular carcinoma. We aimed to compare the efficacy and safety of sorafenib to that of selective internal radiotherapy (SIRT) with yttrium-90 ( 90 Y) resin microspheres in patients with hepatocellular carcinoma. Methods SARAH was a multicentre, open-label, randomised, controlled, investigator-initiated, phase 3 trial done at 25 centres specialising in liver diseases in France. Patients were eligible if they were aged at least 18 years with a life expectancy greater than 3 months, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, Child-Pugh liver function class A or B score of 7 or lower, and locally advanced hepatocellular carcinoma (Barcelona Clinic Liver Cancer [BCLC] stage C), or new hepatocellular carcinoma not eligible for surgical resection, liver transplantation, or thermal ablation after a previously cured hepatocellular carcinoma (cured by surgery or thermoablative therapy), or hepatocellular carcinoma with two unsuccessful rounds of transarterial chemoembolisation. Patients were randomly assigned (1:1) by a permutated block method with block sizes two and four to receive continuous oral sorafenib (400 mg twice daily) or SIRT with 90 Y-loaded resin microspheres 2–5 weeks after randomisation. Patients were stratified according to randomising centre, ECOG performance status, previous transarterial chemoembolisation, and presence of macroscopic vascular invasion. The primary endpoint was overall survival. Analyses were done on the intention-to-treat population; safety was assessed in all patients who received at least one dose of sorafenib or underwent at least one of the SIRT work-up exams. This study has been completed and the final results are reported here. The trial is registered with ClinicalTrials.gov, number NCT01482442. Findings Between Dec 5, 2011, and March 12, 2015, 467 patients were randomly assigned; after eight patients withdrew consent, 237 were assigned to SIRT and 222 to sorafenib. In the SIRT group, 53 (22%) of 237 patients did not receive SIRT; 26 (49%) of these 53 patients were treated with sorafenib. Median follow-up was 27·9 months (IQR 21·9–33·6) in the SIRT group and 28·1 months (20·0–35·3) in the sorafenib group. Median overall survival was 8·0 months (95% CI 6·7–9·9) in the SIRT group versus 9·9 months (8·7–11·4) in the sorafenib group (hazard ratio 1·15 [95% CI 0·94–1·41] for SIRT vs sorafenib; p=0·18). In the safety population, at least one serious adverse event was reported in 174 (77%) of 226 patients in the SIRT group and in 176 (82%) of 216 in the sorafenib group. The most frequent grade 3 or worse treatment-related adverse events were fatigue (20 [9%] vs 41 [19%]), liver dysfunction (25 [11%] vs 27 [13%]), increased laboratory liver values (20 [9%] vs 16 [7%]), haematological abnormalities (23 [10%] vs 30 [14%]), diarrhoea (three [1%] vs 30 [14%]), abdominal pain (six [3%] vs 14 [6%]), increased creatinine (four [2%] vs 12 [6%]), and hand-foot skin reaction (one [ vs 12 [6%]). 19 deaths in the SIRT group and 12 in the sorafenib group were deemed to be treatment related. Interpretation In patients with locally advanced or intermediate-stage hepatocellular carcinoma after unsuccessful transarterial chemoembolisation, overall survival did not significantly differ between the two groups. Quality of life and tolerance might help when choosing between the two treatments. Funding Sirtex Medical Inc.
Published: 2017
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50. Hépatite aiguë chez un consommateur régulier de cocaïne par voie inhalée : à propos d’un cas

Author: Matthieu Lesbordes, Emilie Bouquet, Marie-Christine Perault-Pochat, Stéphanie Pain, Pierre Levillain, Bernard Fauconneau, and Christine Silvain
Subjects: Pharmacology (medical)
Abstract: Introduction La cocaine, alcaloide et puissant psychostimulant, est consommee le plus souvent en situation recreationnelle par voie sniffee, inhalee ou injectee. Une majoration de sa consommation et de sa purete est observee en France ces dernieres annees. Sa toxicite sur le systeme nerveux central et cardiovasculaire est bien documentee. Methodes Nous rapportons ici un cas d’hepatite aigue toxique a la cocaine par voie inhalee. Resultats Il s’agit d’un homme âge de 31 ans, consommateur regulier de cocaine par voie inhalee, ancien heroinomane substitue par methadone, hospitalise pour l’exploration d’infiltrats pulmonaires radiologiques dans un contexte de dyspnee et de douleurs diffuses. Le bilan d’entree montre une legere cytolyse (transaminases : 1,5 N) sans insuffisance hepatocellulaire. Deux jours plus tard, les douleurs abdominales s’amplifient et sont associees a une asthenie. Le bilan biologique revele une cytolyse avec insuffisance hepatocellulaire (ASAT : 39 N ; ALAT : 40,6 N ; PAL : 1,3 N ; GGT : 1,4 N ; bilirubine : N ; TP : 42 % ; facteur V : 30 % ; CPK : N). Les serologies virales sont negatives, de meme que les antigenuries legionelle, pneumocoque, la recherche de leptospirose et le bilan auto-immun. La recherche urinaire de cocaine a J8 est negative (absence de screening). L’histologie hepatique objective une necrose hepatocellulaire centrolobulaire, plus rarement mediolobulaire epargnant les zones periportales ainsi que de rares images de steatose microvacuolaire. Il decede a J16 dans un contexte de choc cardiogenique refractaire. Discussion Les elements chronologiques et l’histologie hepatique sont en faveur du role de la cocaine, les autres causes ayant ete eliminees et la recherche urinaire de cocaine realisee trop tardivement. Les hepatites aigues toxiques a la cocaine sont rares, elles surviennent generalement dans les heures ou les jours suivant une overdose. Les transaminases sont elevees et les phosphatases alcalines legerement augmentees. Le TP chute rapidement et la bilirubine commence a croitre 2 a 3 jours plus tard. L’histologie hepatique montre le plus souvent une necrose centrolobulaire ainsi qu’une steatose. Les deces sont frequents dans un contexte de defaillance multiviscerale. Les cliniciens doivent garder a l’esprit que la cocaine peut induire des hepatites toxiques qui peuvent conduire au deces.
Published: 2018
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