Author: "Victor de Ledinghen" / Topic: internal medicine - Searchworks@Jio Institute Digital Library Search Results

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1. Positive predictive value of sustained virologic response 4 weeks posttreatment for achieving sustained virologic response 12 weeks posttreatment in patients receiving glecaprevir/pibrentasvir in Phase 2 and 3 clinical trials

Author: Douglas E. Dylla, Giuliano Rizzardini, Zhenyi Xue, Julio A. Gutierrez, Margaret Burroughs, Victor de Ledinghen, Jose Luis Calleja, Mitchell L. Shiffman, Stephen T. Barclay, and E.J. Gane
Subjects: Cyclopropanes, medicine.medical_specialty, Aminoisobutyric Acids, Pyrrolidines, Cirrhosis, Genotype, Proline, Sustained Virologic Response, Lactams, Macrocyclic, Concordance, Hepatitis C virus, Hepacivirus, medicine.disease_cause, Antiviral Agents, Gastroenterology, Liver disease, Leucine, Predictive Value of Tests, Quinoxalines, Virology, Internal medicine, medicine, Humans, Imputation (statistics), Sulfonamides, Hepatology, business.industry, Glecaprevir, Hepatitis C, Chronic, medicine.disease, Pibrentasvir, Clinical trial, Treatment Outcome, Infectious Diseases, Benzimidazoles, business
Abstract: Sustained virologic response at posttreatment Week 12 (SVR12) is the widely accepted efficacy endpoint for direct-acting antiviral agents. Those with hepatitis C virus (HCV) are presenting younger with milder liver disease, potentially reducing need for long-term liver posttreatment monitoring. This analysis aimed to determine the positive predictive value (PPV) of SVR at posttreatment Week 4 (SVR4) for achieving SVR12 in patients with HCV, without cirrhosis or with compensated cirrhosis, receiving glecaprevir/pibrentasvir (G/P) in clinical trials. An integrated dataset from 20 Phase 2 and 3 clinical trials of G/P was evaluated in patients with 8-, 12- or 16-week treatment duration consistent with the current label (label-consistent group), and in all patients regardless of treatment duration consistency with the current label (overall group). Sensitivity analyses handled missing data either by backward imputation or were excluded. SVR4 PPV, negative predictive value (NPV), sensitivity and specificity were calculated for achieving SVR12 in both groups, and by treatment duration in the label-consistent group. SVR was defined as HCV ribonucleic acidlower limit of quantification. The label-consistent group and overall group included 2890 and 4390 patients, respectively. PPV of SVR4 for SVR12 was99% in both groups regardless of treatment duration. Not achieving SVR4 had 100% NPV and sensitivity for all groups. SVR4 measure had 79.5% specificity for identifying patients who did not achieve SVR12. Across 20 Phase 2/3 clinical trials of G/P, SVR4 was highly predictive of SVR12. Long-term follow-up to confirm SVR may not be necessary for certain populations of patients with HCV.
Published: 2021

2. 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

3. Subclinical proximal tubulopathy in hepatitis B: The roles of nucleot(s)ide analogue treatment and the hepatitis B virus

Author: Thierry Poynard, Guillaume Lassailly, Juliette Foucher, Manh-Thông Dao, Xavier Duval, Isabelle Hourmand-Ollivier, Séverine Hommel, Vincent Di Martino, Pierre-Henri Bernard, Dominique Larrey, Nathalie Boyer, Anais Labrunie, Marc Bardou, Paul Carrier, Marilyne Debette-Gratien, Marie Essig, Eric Nguyen-Khac, Armand Abergel, Victor de Ledinghen, Véronique Loustaud-Ratti, Claire Vanlemmens, Nathalie Ganne-Carrié, Anne Gervais, Jean-Baptiste Hiriart, Fouchard-Hubert Isabelle, Christine Aurières, Pauline Pinet, Thierry Thevenot, Jérémie Jacques, Philippe Mathurin, Dominique Thabut, Christophe Renou, Daniel Cohen, Marianne Maynard, Valérie Canva, Julien Vergniol, Bertrand Hanslik, Anaïs Brayette, Sophie Alain, Matthieu Schnee, Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Pôle Universitaire d’Addictologie en Limousin, CH Esquirol [Limoges] (CH Esquirol), Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Plate forme de bioinformatique et biostatistique (CEBIMER), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), 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), Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 (GRAP), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Maladies infectieuses et tropicales [CHU Limoges], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hepatology, Hopital, Physiopathologie des Maladies Inflammatoires de l'Intestin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], Service d'Hépato-gastro-entérologie et oncologie digestive (CHU de Bordeaux), CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], 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), Paris School of Economics (PSE), Université Paris 1 Panthéon-Sorbonne (UP1)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-École des Ponts ParisTech (ENPC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Paris Jourdan Sciences Economiques (PJSE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), 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 Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Investigation Clinique 1432 (Dijon) - Module Plurithématique : Périnatalité Cancérologie Handicap et Ophtalmologie (CIC-P803), Université de Bourgogne (UB)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Normandie Université (NU), Service d'Hépatologie [CHRU Besançon], Hôpital Haut-Lévêque [CHU Bordeaux], Hôpital Claude Huriez [Lille], CHU Lille, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], 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), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Service de gastroentérologie (CHD Vendee - Hopital Les Oudairies, La Roche Sur Yon), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Hôpital Saint-Éloi [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), 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), Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), Épidémiologie et recherches translationnelles sur les maladies rénales et cardiovasculaires (EPREC) (U1018 (Équipe 5)), 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-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, Service Néphrologie/Dialyse [AP-HP Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], 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 (UPC)-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 (UPC), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], 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), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], and Hôpital Charles Nicolle [Rouen]-CHU Rouen
Subjects: Hepatitis B virus, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Population, Renal function, medicine.disease_cause, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Nucleoside analogues, Internal medicine, medicine, Cumulative incidence, Renal insufficiency, education, education.field_of_study, Hepatology, business.industry, Proximal tubulopathy, Incidence (epidemiology), Hazard ratio, Entecavir, Hepatitis B, medicine.disease, 030220 oncology & carcinogenesis, Prospective Study, 030211 gastroenterology & hepatology, business, Biomarkers, medicine.drug
Abstract: International audience; BACKGROUND The recommended monitoring tools for evaluating nucleot(s)ide analogue renal toxicity, such as estimated glomerular filtration rate (eGFR) and phosphatemia, are late markers of proximal tubulopathy. Multiple early markers are available, but no consensus exists on their use. AIM To determine the 24 mo prevalence of subclinical proximal tubulopathy (SPT), as defined with early biomarkers, in treated vs untreated hepatitis B virus (HBV)-monoinfected patients. METHODS A prospective, non-randomized, multicenter study of HBV-monoinfected patients with a low number of renal comorbidities was conducted. The patients were separated into three groups: Naive, starting entecavir (ETV) treatment, or starting tenofovir disoproxil (TDF) treatment. Data on the early markers of SPT, the eGFR and phosphatemia, were collected quarterly. SPT was defined as a maximal tubular reabsorption of phosphate/eGFR below 0.8 mmoL/L and/or uric acid fractional excretion above 10%. The prevalence and cumulative incidence of SPT at month 24 (M24) were calculated. Quantitative data were analyzed using analyses of variance or Kruskal-Wallis tests, whereas chi-squared or Fisher's exact tests were used to analyze qualitative data. Multivariate analyses were used to adjust for any potential confounding factors. RESULTS Of the 196 patients analyzed, 138 (84 naive, 28 starting ETV, and 26 starting TDF) had no SPT at inclusion. At M24, the prevalence of SPT was not statistically different between naive and either treated group (21.1% vs 30.7%, P < 0.42 and 50.0% vs 30.7%, P = 0.32 for ETV and TDF, respectively); no patient had an eGFR lower than 50 mL/min/1.73 m(2) or phosphatemia less than 0.48 mmoL/L. In the multivariate analysis, no explanatory variables were identified after adjustment. The cumulative incidence of SPT over 24 mo (25.5%, 13.3%, and 52.9% in the naive, ETV, and TDF groups, respectively) tended to be higher in the TDF group vs the naive group (hazard ratio: 2.283, P = 0.05). SPT-free survival at M24 was 57.6%, 68.8%, and 23.5% for the naive, ETV, and TDF groups, respectively. The median survival time without SPT, evaluated only in the TDF group, was 5.9 mo. CONCLUSION The prevalence and incidence of SPT was higher in TDF-treated patients compared to naive patients. SPT in the naive population suggests that HBV can induce renal tubular toxicity.
Published: 2020

4. 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

5. Liver transplantation as a rescue therapy for severe neurologic forms of Wilson disease

Author: Aurélia Poujois, Rodolphe Sobesky, Wassilios G. Meissner, Anne-Sophie Brunet, Emmanuel Broussolle, Chloé Laurencin, Laurence Lion-François, Olivier Guillaud, Alain Lachaux, François Maillot, Jérémie Belin, Ephrem Salamé, Claire Vanlemmens, Bruno Heyd, Céline Bellesme, Dalila Habes, Christophe Bureau, Fabienne Ory-Magne, Pascal Chaine, Jean-Marc Trocello, Daniel Cherqui, Didier Samuel, Victor de Ledinghen, Jean-Charles Duclos-Vallée, France Woimant, National reference Centre for Wilson's Disease [Paris] (CRMR Wilson), Service de neurologie [Univ. Paris VII], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service d'Electroneuromyographie et Service de Neurologie C [Hôpital Pierre Wertheimer - HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université de Lyon, Département d'hépatologie, Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Groupe de Recherche en Economie Théorique et Appliquée (GREThA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Hôpital Claude Huriez [Lille], CHU Lille, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Badji Mokhtar de Annaba, CHU Toulouse [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Paul Brousse, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Hôpital Purpan [Toulouse], and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL)
Subjects: Male, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Drug Resistance, Liver transplantation, Severity of Illness Index, Disability Evaluation, Young Adult, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Hepatolenticular Degeneration, Liver Function Tests, Modified Rankin Scale, Internal medicine, Severity of illness, Humans, Medicine, Survival rate, Retrospective Studies, medicine.diagnostic_test, business.industry, Parkinsonism, Retrospective cohort study, medicine.disease, Magnetic Resonance Imaging, Liver Transplantation, 3. Good health, Survival Rate, Female, 030211 gastroenterology & hepatology, Neurology (clinical), business, Liver function tests, 030217 neurology & neurosurgery
Abstract: ObjectiveTo evaluate the effect of liver transplantation (LT) in patients with Wilson disease (WD) with severe neurologic worsening resistant to active chelation.MethodsFrench patients with WD who underwent LT for pure neurologic indication were retrospectively studied. Before LT and at the last follow-up, neurologic impairment was evaluated with the Unified Wilson's Disease Rating Scale (UWDRS) score, disability with the modified Rankin Scale (mRS) score, and hepatic function with the Model for End-stage Liver Disease score, together with the presence of a Kayser-Fleischer ring (KFR), brain MRI scores, and copper balance. The survival rate and disability at the last follow-up were the coprimary outcomes; evolution of KFR and brain MRI were the secondary outcomes. Prognosis factors were further assessed.ResultsEighteen patients had LT. All were highly dependent before LT (median mRS score 5). Neurologic symptoms were severe (median UWDRS score 105), dominated by dystonia and parkinsonism. The cumulated survival rate was 88.8% at 1 year and 72.2% at 3 and 5 years. At the last follow-up, 14 patients were alive. Their mRS and UWDRS scores improved (p< 0.0001 andp= 0.0003). Eight patients had a major improvement (78% decrease of the UWDRS score), 4 a moderate one (41% decrease), and 2 a stable status. KFR and brain MRI scores improved (p= 0.0007). Severe sepsis (p= 0.011) and intensive care unit admission (p= 0.001) before LT were significantly associated with death.ConclusionsLT is a rescue therapeutic option that should be carefully discussed in selected patients with neurologic WD resistant to anticopper therapies (chelators or zinc salts) as it might allow patients to gain physical independency with a reasonable risk.Classification of evidenceThis study provides Class IV evidence that for patients with WD with severe neurologic worsening resistant to active pharmacologic therapy, LT might decrease neurologic impairment.
Published: 2020

6. Monitoring Occurrence of Liver-Related Events and Survival by Transient Elastography in Patients With Nonalcoholic Fatty Liver Disease and Compensated Advanced Chronic Liver Disease

Author: Marco Enea, Vincent Wai-Sun Wong, Aline Keyrouz, Anna Ludovica Fracanzani, Antonio Craxì, Sergio Mazzola, Javier Ampuero, Mauro Viganò, Jérôme Boursier, Salvatore Petta, Ramy Younes, Victor de Ledinghen, Annalisa Berzigotti, Giada Sebastiani, Manuel Romero-Gómez, Marraud des Grottes, Calogero Cammà, Elisabetta Bugianesi, Vito Di Marco, Yuly P. Mendoza, Grazia Pennisi, Fonds de Recherche du Québec, McGill University, I Gastroenterology Unit, Department of Medicine, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Università degli studi di Palermo - University of Palermo, Salvatore Petta, Giada Sebastiani, Mauro Viganò, Javier Ampuero, Vincent Wai-Sun Wong, Jerome Boursier, Annalisa Berzigotti, Elisabetta Bugianesi, Anna Ludovica Fracanzani, Calogero Cammà, Marco Enea, Marraud des Grotte, Vito Di Marco, Ramy Youne, Aline Keyrouz, Sergio Mazzola, Yuly Mendoza, Grazia Pennisi, Manuel Romero-Gomez, Antonio Craxì, and Victor de Ledinghen
Subjects: Liver Cirrhosis, medicine.medical_specialty, Carcinoma, Hepatocellular, Settore MED/09 - Medicina Interna, NASH, cACLD, prognostic factor, steatohepatitis, [SDV]Life Sciences [q-bio], Prognostic Factor, Steatohepatitis, Gastrointestinal Hemorrhage, Humans, Liver, Retrospective Studies, Elasticity Imaging Techniques, Esophageal and Gastric Varices, Liver Neoplasms, Non-alcoholic Fatty Liver Disease, 610 Medicine & health, Chronic liver disease, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, Ascites, Nonalcoholic fatty liver disease, medicine, ComputingMilieux_MISCELLANEOUS, Hepatology, business.industry, steatohepatiti, Carcinoma, Hazard ratio, Hepatocellular, medicine.disease, 3. Good health, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, medicine.symptom, Transient elastography, business
Abstract: [Background & Aims] Patients with advanced fibrosis related to nonalcoholic fatty liver disease (NAFLD) are at risk of developing hepatic and extrahepatic complications. We investigated whether, in a large cohort of patients with NAFLD and compensated advanced chronic liver disease, baseline liver stiffness measurements (LSMs) and their changes can be used to identify patients at risk for liver-related and extrahepatic events., [Methods] We performed a retrospective analysis of consecutive patients with NAFLD (n = 1039) with a histologic diagnosis of F3–F4 fibrosis and/or LSMs>10 kPa, followed for at least 6 months, from medical centers in 6 countries. LSMs were made by FibroScan using the M or XL probe and recorded at baseline and within 1 year from the last follow-up examination. Differences between follow up and baseline LSMs were categorized as: improvement (reduction of more than 20%), stable (reduction of 20% to an increase of 20%), impairment (an increase of 20% or more). We recorded hepatic events (such as liver decompensation, ascites, encephalopathy, variceal bleeding, jaundice, or hepatocellular carcinoma [HCC]) and overall and liver-related mortality during a median follow-up time of 35 months (interquartile range, 19–63 months)., [Results] Based on Cox regression analysis, baseline LSM was independently associated with occurrence of hepatic decompensation (hazard ratio [HR], 1.03; 95% CI, 1.02–1.04; P < .001), HCC (HR, 1.03; 95% CI, 1.00–1.04; P = .003), and liver-related death (HR, 1.02; 95% CI, 1.02–1.03; P = .005). In 533 patients with available LSMs during the follow-up period, change in LSM was independently associated with hepatic decompensation (HR, 1.56; 95% CI, 1.05–2.51; P = .04), HCC (HR, 1.72; 95% CI, 1.01–3.02; P = .04), overall mortality (HR, 1.73; 95% CI, 1.11–2.69; P = .01), and liver-related mortality (HR, 1.96; 95% CI, 1.10–3.38; P = .02)., [Conclusions] In patients with NAFLD and compensated advanced chronic liver disease, baseline LSM and change in LSM are associated with risk of liver-related events and mortality., Giada Sebastiani is supported by a Junior 1 and 2 Salary Award from Fonds de Recherche Santé du Québec (#27127 and #267806) and research salary from the Department of Medicine of McGill University.
Published: 2021

7. Long-term prognosis of patients with alcohol-related liver disease or non-alcoholic fatty liver disease according to metabolic syndrome or alcohol use

Author: Juliette Foucher, Marie Irles-Depe, Dan Dutartre, Marie Decraecker, Victor de Ledinghen, Faiza Chermak, Adele Delamarre, Hortense Marraud des Grottes, and Jean-Baptiste Hiriart
Subjects: Metabolic Syndrome, medicine.medical_specialty, education.field_of_study, Hepatology, Alcohol Drinking, business.industry, Proportional hazards model, Population, Fatty liver, nutritional and metabolic diseases, medicine.disease, Prognosis, Gastroenterology, Cohort Studies, Liver disease, Non-alcoholic Fatty Liver Disease, Internal medicine, Clinical endpoint, Medicine, Humans, Metabolic syndrome, business, Complication, education, Cohort study
Abstract: Background & aims The boundary between non-alcoholic (NAFLD) and alcohol-related liver disease (ALD) is based on alcohol consumption. However, metabolic syndrome and alcohol use frequently co-exist. The aim of this study was to determine prognostic factors of long-term morbidity and mortality in patients with NAFLD or ALD. Methods From 2003 to 2016, all consecutive NAFLD or ALD patients were prospectively included in this cohort study. We evaluated overall survival, specific cause of mortality, and occurrence of any complication. The primary endpoint was analysed by the Kaplan-Meier method, secondary endpoints were estimated by Gray test method or logistic regressions. Factors independently associated with overall mortality and morbidity were identified by a multivariate Cox model. Results A total of 3,365 patients (1,667 with ALD and 1,698 with NAFLD) were included. Median follow-up was 54 months (range: 30-86) and 563 subjects died. In the overall population, overall mortality was higher in patients with ALD (HR: 10.1 [7.57-13.3]), and with weekly alcohol consumption > 7 units (HR:1.66 [1.41-1.96]). Liver-related mortality was higher in patients with ALD (HR: 11 [7.27-16.5]). In the NAFLD group, weekly alcohol consumption > 1 unit was associated with higher overall mortality (HR: 1.9 [1.1-3.4]), and weekly alcohol consumption > 7 units was associated with higher overall morbidity (OR: 1.89 [1.61-2.21]). In the ALD group, the presence of metabolic syndrome was associated with higher overall (HR:1.27 [1.02-1.57]), and liver (HR: 1.47 [1.1-1.96]) mortalities, and overall (OR: 1.46 [1.14-1.88]), liver (OR: 1.46 [1.14-1.88]) morbidities. Conclusion In fatty liver diseases, light alcohol consumption and metabolic syndrome are prognosis cofactors.
Published: 2021

8. 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

9. Comorbidities Are Associated with Fibrosis in NAFLD Subjects: A Nationwide Study (NASH-CO Study)

Author: Karine Lacombe, Jérôme Boursier, Lawrence Serfaty, Philippe Mathurin, Victor de Ledinghen, Marie Zins, Marcel Goldberg, Oumarou Nabi, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), 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), Services des Maladies Infectieuses et Tropicales [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 Hospitalier Régional Universitaire [Lille] (CHRU Lille), Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Hôpital de Hautepierre [Strasbourg], 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), Gestionnaire, Hal Sorbonne Université, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre de Recherche Saint-Antoine (CR Saint-Antoine), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP]
Subjects: Adult, Liver Cirrhosis, medicine.medical_specialty, Physiology, [SDV]Life Sciences [q-bio], Population, Forns Index, Renal function, Gastroenterology, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Fibrosis, Non-alcoholic Fatty Liver Disease, Risk Factors, Internal medicine, Chronic kidney disease, medicine, Humans, Fatty Liver Index, Renal Insufficiency, Chronic, education, Cancer, education.field_of_study, business.industry, Fatty liver, Hepatology, medicine.disease, Cardiovascular disease, Colorectal cancer, 3. Good health, [SDV] Life Sciences [q-bio], Cardiovascular Diseases, 030220 oncology & carcinogenesis, Cohort, Population study, 030211 gastroenterology & hepatology, business, Glomerular Filtration Rate
Abstract: International audience; Background: The relationship between the severity of NAFLD and extra-hepatic events such as cardiovascular disease (CVD), extra-hepatic cancer (EHC) or chronic kidney diseases (CKD) has not been clearly investigated in the general population.Aims: The aim of this study was to assess whether the severity of fibrosis in NAFLD subjects was associated with extra-hepatic diseases based on noninvasive markers in a large population-based cohort.Methods: The study population included a cohort of 118,664 participants from the nationwide CONSTANCES cohort. After excluding individuals with excessive alcohol consumption and other causes of liver disease, 102,344 were included. The noninvasive diagnosis of NAFLD and fibrosis was performed using a combination of the Fatty Liver Index (FLI) and the Forns Index. The history of CVD or EHC was recorded by a physician, and CKD was defined by a glomerular filtration rate < 60 ml/mn.Results: The prevalence of NAFLD (FLI > 60) was 18.2%, 10% with mild fibrosis (Forns Index < 4.2), 7.7% with intermediate fibrosis (Forns Index 4.2-6.9), and 0.4% with advanced fibrosis (Forns Index > 6.9). The prevalence of CVD, EHC, or CKD increased significantly with the severity of fibrosis (p < 0.0001). When adjusted for demographic, metabolic risk factors, and smoking, NAFLD with intermediate or advanced fibrosis remained associated with CVD (OR 1.36, p < 0.0001 and OR 3.07, p < 0.0001, respectively), EHC (OR 1.24, p = 0.001 and OR 1.64, p = 0.004, respectively), and CKD (OR 1.18, p = 0.03 and OR 2.09, p < 0.0001, respectively).Conclusions: In a large adult population-based cohort, there is a dose-dependent relationship between the severity of fibrosis and CVD, EHC, or CKD in NAFLD subjects.
Published: 2021

10. Refining the Baveno VI elastography criteria for the definition of compensated advanced chronic liver disease

Author: Sebastian Mueller, Paul Calès, Omar Elshaarawy, Jérôme Boursier, Emmanuel Tsochatzis, Aleksander Krag, Umberto Arena, Victor de Ledinghen, Margarita Papatheodoridi, Maja Thiele, Massimo Pinzani, Laurent Castera, Edgar Brodkin, George V. Papatheodoridis, Fabio Marra, Georgios Markakis, Jean Baptiste Hiriart, Monica Lupsor-Platon, Audrey Payancé, Vincenza Calvaruso, Fabrizio Bronte, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Papatheodoridi M., Hiriart J.B., Lupsor-Platon M., Bronte F., Boursier J., Elshaarawy O., Marra F., Thiele M., Markakis G., Payance A., Brodkin E., Castera L., Papatheodoridis G., Krag A., Arena U., Mueller S., Cales P., Calvaruso V., de Ledinghen V., Pinzani M., and Tsochatzis E.A.
Subjects: 0301 basic medicine, Alcoholic liver disease, medicine.medical_specialty, Cirrhosis, [SDV]Life Sciences [q-bio], Chronic liver disease, Asymptomatic, Gastroenterology, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Internal medicine, NAFLD, medicine, Viral hepatitis, 10. No inequality, Portal hypertension, ComputingMilieux_MISCELLANEOUS, Cirrhosi, Hepatology, medicine.diagnostic_test, business.industry, Fatty liver, medicine.disease, 3. Good health, 030104 developmental biology, Fibroscan, Liver biopsy, FIB-4, 030211 gastroenterology & hepatology, medicine.symptom, Transient elastography, business
Abstract: Background: The Baveno VI consensus proposed a dual liver stiffness (LS) by transient elastography threshold of 15 kPa for excluding and diagnosing compensated advanced chronic liver disease (cACLD) in the absence of other clinical signs. Herein, we aimed to validate these criteria in a real-world multicentre study. Methods: We included 5,648 patients (mean age 51 ± 13 years, 53% males) from 10 European liver centres who had a liver biopsy and LS measurement within 6 months. We included patients with chronic hepatitis C (n = 2,913, 52%), non-alcoholic fatty liver disease (NAFLD, n = 1,073, 19%), alcohol-related liver disease (ALD, n = 946, 17%) or chronic hepatitis B (n = 716, 13%). cACLD was defined as fibrosis stage ≥F3. Results: Overall, 3,606 (66%) and 987 (18%) patients had LS 15 kPa, respectively, while cACLD was histologically confirmed in 1,772 (31%) patients. The cut-offs of 15 kPa showed 75% sensitivity and 96% specificity to exclude and diagnose cACLD, respectively. Examining the ROC curve, a more optimal dual cut-off at 12 kPa, with 91% sensitivity and 92% specificity for excluding and diagnosing cACLD (AUC 0.87; 95% CI 0.86–0.88; p 15 kPa dual cut-offs, we found that the 12 kPa dual cut-offs have better diagnostic accuracy in cACLD. Lay summary: The term compensated advanced chronic liver disease (cACLD) was introduced in 2015 to describe the spectrum of advanced fibrosis and cirrhosis in asymptomatic patients. It was also suggested that cACLD could be diagnosed or ruled out based on specific liver stiffness values, which can be non-invasively measured by transient elastography. Herein, we assessed the suggested cut-off values and identified alternative values that offered better overall accuracy for diagnosing or ruling out cACLD.
Published: 2021

11. Predictive Factors for Hepatocellular Carcinoma in Chronic Hepatitis B Using Structural Equation Modeling: A Prospective Cohort Study

Author: Jean-Pierre Bronowicki, Clovis Lusivika-Nzinga, Jean-Charles Duclos-Vallée, Ghassan Riachi, Anne Minello, Thomas Decaens, Louis d’Alteroche, Fabrice Carrat, Isabelle Portal, François Raffi, Fabien Zoulim, Sophie Metivier, Véronique Loustaud-Ratti, François Habersetzer, Jérôme Gournay, Olivier Chazouillères, Paul Calès, Victor de Ledinghen, Xavier Causse, Stanislas Pol, Céline Dorival, Isabelle Rosa, Dominique Larrey, Tarik Asselah, Marc Bourlière, Claire Geist, Nathanael Lapidus, Laurent Lam, Moana Gelu-Simeon, Laurent Alric, Vincent Leroy, Hélène Fontaine, Armand Abergel, Nathalie Ganne, Dominique Thabut, Philippe Mathurin, Albert Tran, Dominique Guyader, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Saint-Joseph [Marseille], Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, 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 de Paris (UP), Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, CRHU Nancy, Physiopathologie des Maladies Inflammatoires de l'Intestin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, 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), 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), CHU Pontchaillou [Rennes], 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), 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), CHI Créteil, Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Régional d'Orléans (CHRO), 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), Service d'hépatologie [CHU Saint-Antoine], CHU Pointe-à-Pitre/Abymes [Guadeloupe], 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), Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), CHU Toulouse [Toulouse], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut 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), CHU Rouen, Normandie Université (NU), Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de 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)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital de la Timone [CHU - APHM] (TIMONE), Immunité Innée - Innate Immunity, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], The ANRS CO22 HEPATHER cohort is sponsored and funded by INSERM‐ANRS and conducted in collaboration with Association Française pour l'étude du Foie (AFEF). The cohort received supports from ANR (Agence Nationale de la Recherche), DGS (Direction Générale de la Santé), MSD, Janssen, Gilead, Abbvie, BMS, and Roche., Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Pathologies biliaires, fibrose et cancer du foie [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), 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 ), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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 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), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 ), 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, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), 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), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: Male, Liver Cancer, medicine.medical_specialty, Hepatocarcinogenesis, Hepatitis B virus, Carcinoma, Hepatocellular, Epidemiology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Liver transplantation, Sciences du Vivant [q-bio]/Cancer, medicine.disease_cause, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Hepatitis B, Chronic, [SDV.CAN] Life Sciences [q-bio]/Cancer, Risk Factors, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, Aged, Hepatology, business.industry, Liver Neoplasms, Carcinoma, Hepatocellular, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cohort, 030211 gastroenterology & hepatology, Metabolic syndrome, business, Liver cancer
Abstract: International audience; BACKGROUND and AIMS: The factors predicting hepatocellular carcinoma (HCC) occurrence in chronic hepatitis B need to be precisely known to improve its detection. We identified pathways and individual predictive factors associated with HCC in the ANRS CO22 HEPATHER cohort. METHODS: The study analyzed HBV-infected patients recruited at 32 French expert hepatology centers from August 6, 2012, to December 31, 2015. We excluded patients with chronic HCV, HDV and a history of HCC, decompensated cirrhosis or liver transplantation. Structural equation models were developed to characterize the causal pathways leading to HCC occurrence. The association between clinical characteristics (age, gender, body-mass index, liver fibrosis, alcohol consumption, smoking status, diabetes, hypertension, dyslipidemia, alpha-fetoprotein, HBV DNA levels, antiviral therapy) and incident HCC was quantified. RESULTS: Among the 4,489 patients included, 33 patients reported incident HCC. The median follow-up was 45.2 months. Age (β = 0.18 by decade, 95% CI 0.14-0.23), male gender (β = 0.23, 95% CI 0.18-0.29), metabolic syndrome (β = 0.28, 95% CI 0.22-0.33), alcohol consumption (β = 0.09, 95% CI 0.05-0.14) and HBV DNA (β = 0.25, 95% CI 0.17-0.34) had a significant and direct effect on the occurrence of advanced liver fibrosis. Liver fibrosis (β = 0.71, 95% CI 0.55-0.87) predicted, in turn, the occurrence of HCC. CONCLUSIONS: Liver fibrosis mediates the effects of age, gender, alcohol, metabolic syndrome and HBV DNA on the occurrence of HCC. Elderly men with chronic hepatitis B, risky alcohol use, advanced liver fibrosis, metabolic syndrome and high HBV DNA levels should be monitored closely to detect the development of HCC.
Published: 2021

12. Large-scale screening of lipase acid deficiency in at risk population

Author: Victor de Ledinghen, Marie-Thérèse Abi Warde, Eric Nguyen-Khac, Marietta Musikas, Soumeya Bekri, Eloi Blanchet, Alice Thebaut, Isabelle Tragin, Anaïs Brassier, Dominique Larrey, Sarah Snanoudj, Myriam Dabbas, Michel Krempf, Edouard Bardou-Jacquet, Carine Pilon, Denis Ouzan, Corinne Borderon, Jean-Marc Perarnau, Armand Abergel, Maeva Guillaume, Reda Belbouab, Thierry Thevenot, Claire Carette, Valérie Triolo, Jean-Pierre Bronowicki, Hélène Dranguet, Jean Ferrières, Rodolphe Anty, Sabrina Vergnaud, Vincent Leroy, Vlad Ratzlu, Bertrand Cariou, Bruno Vergès, Abdellah Tebani, Bénédicte Sudrié-Arnaud, Hela Boudabous, Florence Lacaille, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), Université de Tunis El Manar (UTM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), CHU Clermont-Ferrand, CHU Strasbourg, 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], Centre Hospitalo-Universitaire Mustapha Bacha, Service de psychiatrie, groupe hospitalier de La Rochelle-Ré-Aunis, CH La Rochelle, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre hospitalier universitaire de Nantes (CHU Nantes), 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), CHU Pessac, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Clinique Bretéché [Nantes], 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), 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), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), 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), Institut Arnault Tzanck, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, CHU Grenoble, This research was funded by Alexion Pharmaceuticals., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université Nice Sophia Antipolis (... - 2019) (UNS), 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), CRHU Nancy, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), and Jonchère, Laurent
Subjects: 0301 basic medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Acid lipase deficiency, DBS, Spleen, Dried blood spot, Lysosomal acid lipase deficiency, Biochemistry, Gastroenterology, CESD, Cholesterol ester storage disease, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Lysosome, Internal medicine, medicine, Humans, Allele, business.industry, Biochemistry (medical), Infant, Newborn, Wolman Disease, Lipase, General Medicine, LAL, Sterol Esterase, medicine.disease, Phenotype, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, Wolman, 030220 oncology & carcinogenesis, Cohort, Screening, Female, Cholesterol Esters, business
Abstract: International audience; BACKGROUND: Lysosomal acid lipase deficiency (LALD, OMIM#278000) is a rare lysosomal disorder with an autosomal recessive inheritance. The main clinical manifestations are related to a progressive accumulation of cholesteryl esters, triglycerides or both within the lysosome in different organs such as the liver, spleen, and cardiovascular system. A wide range of clinical severity is associated with LALD including a severe very rare antenatal/neonatal/infantile phenotype named Wolman disease and a late-onset form named cholesteryl ester storage disease (CESD). METHODS: This study aimed to investigate a cohort of at-risk patients (4174) presenting with clinical or biological signs consistent with LALD using the assessment of LAL activity on dried blood spots. RESULTS: LAL activity was lower than 0.05 nmol/punch/L (cut-off: 0.12) in 19 patients including 13 CESD and 6 Wolman. Molecular study has been conducted in 17 patients and succeeded in identifying 34 mutated alleles. Fourteen unique variants have been characterized, 7 of which are novel. CONCLUSION: This study allowed to identify a series of patients and expanded the molecular spectrum knowledge of LALD. Besides, a new screening criteria grid based on the clinical/biological data from our study and the literature has been proposed in order to enhance the diagnosis rate in at risk populations.
Published: 2021

13. 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

14. 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, Vincent Di Martino, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Nord, 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), 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), Hôpital Henri Mondor, Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ANRS CO12 CirVir group: Pierre Nahon1, Tarik Asselah2, Dominique Guyader3, Stanislas Pol4, Hélène Fontaine4, Georges-Philippe Pageaux5, Victor De Lédinghen6, Denis Ouzan7, Fabien Zoulim8, Dominique Roulot9, Albert Tran10, Jean-Pierre Bronowicki11, Thomas Decaens12, Ghassan Riachi13, Paul Calès14, Jean-Marie Péron15, Laurent Alric16, Marc Bourlière17, Philippe Mathurin18, Sebastien Dharancy18, Jean-Frédéric Blanc19, Armand Abergel20, Olivier Chazouillères21, Ariane Mallat22, Jean-Didier Grangé23, Pierre Attali24, Louis d’Alteroche25, Claire Wartelle26, Thông Dao27, Dominique Thabut28, Christophe Pilette29, Christine Silvain30, Christos Christidis31, Eric Nguyen-Khac32, Brigitte Bernard-Chabert 33, Sophie Hillaire34, Vincent Di Martino35. 1AP-HP, Hôpital Avicenne, Service d’Hépatologie, Bobigny, Université Sorbonne Paris Nord, Bobigny et INSERM U1138, Université de Paris, 2AP-HP, Hôpital Beaujon, Service d’Hépatologie, and University Paris Diderot, Sorbonne Paris Cité, CRI, UMR 1149, 3CHU Pontchaillou, Service d’Hépatologie, Rennes, 4AP-HP, Hôpital Cochin, Département d’Hépatologie et INSERM UMS20 et U1223, Institut Pasteur, Université Paris Descartes, Paris, 5Hôpital Saint Eloi, Service d’Hépatologie, Montpellier, 6Hôpital Haut-Lévêque, Service d’Hépatologie, Bordeaux, 7Institut Arnaud Tzanck, Service d’Hépatologie, St Laurent du Var, 8Hôpital Hôtel Dieu, Service d’Hépatologie, Lyon, 9AP-HP, Hôpital Avicenne, Service de Medeine Interne, Bobigny, 10CHU de Nice, Service d’Hépatologie, et INSERM U1065, Université de Nice-Sophia-Antipolis, Nice, 11Hôpital Brabois, Service d’Hépatologie, Vandoeuvre-les-Nancy, 12Hôpital Michallon, Service d’Hépatologie, Grenoble, 13Hôpital Charles-Nicolle, Service d’Hépatologie, Rouen, 14CHU d’Angers, Service d’Hépatologie, Angers, 15Hôpital Purpan, Service d’Hépatologie, Toulouse, 16CHU Toulouse, Service de Médecine Interne-Pôle Digestif UMR 152, Toulouse, 17Hôpital Saint Joseph, Service d’Hépatologie, Marseille, 18Hôpital Claude Huriez, Service d’Hépatologie, Lille, 19Hôpital St André, Service d’Hépatologie, Bordeaux, 20Hôpital Hôtel Dieu, Service d’Hépatologie, Clermont-Ferrand, 21AP-HP, Hôpital Saint-Antoine, Service d’Hépatologie, Paris, 22AP-HP, Hôpital Henri Mondor, Service d’Hépatologie, Créteil, 23AP-HP, Hôpital Tenon, Service d’Hépatologie, Paris, 24AP-HP, Hôpital Paul Brousse, Service d’Hépatologie, Villejuif, 25Hôpital Trousseau, Unité d’Hépatologie, CHRU de Tours, 26Hôpital d’Aix-En-Provence, Service d’Hépatologie, Aix-En-Provence, 27Hôpital de la Côte de Nacre, Service d’Hépatologie, Caen, 28AP-HP, Groupe Hospitalier de La Pitié-Salpêtrière, Service d’Hépatologie, Paris, 29CHU Le Mans, Service d’Hépatologie, Le Mans, 30CHU de Poitiers, Service d’Hépatologie, Poitiers, 31Institut Mutualiste Montsouris, Service d’Hépatologie, Paris, 32Hôpital Amiens Nord, Service d’Hépatologie, Amiens, 33Hôpital Robert Debré, Service d’Hépatologie, Reims, 34Hôpital Foch, Service d’Hépatologie, Suresnes, 35Hôpital Jean Minjoz, Service d’Hépatologie, Besançon. France., CIRRAL group: Nathalie Ganne-Carrié1, Cendrine Chaffaut2, Isabelle Archambeaud3, Louis d’Alteroche4, Frédéric Oberti5, Dominique Roulot6, Christophe Moreno7, Alexandre Louvet8, Thông Dao9, Romain Moirand10, Odile Goria11, Eric Nguyen-Khac12, Nicolas Carbonell13, Jean-Charles Duclos-Vallée14, Stanislas Pol15,16, Victor de Ledinghen17, Violaine Ozenne18, Jean Henrion19, Jean-Marie Péron20, Albert Tran21,22, Gabriel Perlemuter23, Xavier Amiot24, Jean-Pierre Zarski25, Sylvie Chevret2. 1AP-HP, Hôpital Avicenne, Service d’Hépatologie, Bobigny, Université Sorbonne Paris Nord, Bobigny et INSERM U1138, Université de Paris, 2SBIM, APHP, Hôpital Saint-Louis, Paris, Inserm, UMR-1153, ECSTRA Team, Paris, France, 3Liver, CHU, Nantes, France, 4Liver Unit, University Hospital, Tours, France, 5Liver Unit, University Hospital, Angers, France, 6AP-HP, Hôpital Avicenne, Service de Médecine Interne, Bobigny, Université Sorbonne Paris Nord, Bobigny, 7Liver unit, CUB Hôpital Erasme, Université Libre de Bruxelles, Belgium, 8Liver Unit, University Hospital, Lille, France, 9Liver Unit, University Hospital, Caen, France, 10Liver Unit, University Hospital, Rennes, France, 11Liver Unit, University Hospital, Rouen, France, 12Liver Unit, University Hospital, Amiens, France, 13 Liver Unit, APHP, CHU Saint-Antoine, Paris, France, 14Liver Unit, APHP, CHU Paul Brousse, Villejuif, France, 15Université Paris Descartes, APHP, Liver Unit, Hôpital Cochin, 16INSERM U1223, Institut Pasteur, Paris, France, 17Hepatology Unit, University Hospital, CHU Bordeaux, France, 18Liver Unit, APHP, CHU Lariboisière, Paris, France, 19Liver Unit, University Hospital, Haine Saint-Paul, Belgium, 20Liver Unit, Universitary Hospital Purpan, University Paul Sabatier III, Toulouse, 21Institut National de la Santé et de la Recherche Médicale (INSERM), U1065, Team 8, 'Hepatic Complications in Obesity', Nice, F-06204, Cedex 3, France, 22University Hospital of Nice, Digestive Centre, Nice, F-06202, Cedex 3, France, 23Liver Unit, University Hospital, Béclère, APHP, Clamart, France, 24Liver Unit, APHP, CHU Tenon, Paris, France, and 25Clinique d’hépato-gastroentérologie pôle Digidune CHU de Grenoble, France
Subjects: Alcoholic liver disease, medicine.medical_specialty, Cirrhosis, primary liver cancer, VIR, virus-related, ECOG Performance Status, [SDV.CAN]Life Sciences [q-bio]/Cancer, MIX, alcohol and virus-related, RC799-869, Gastroenterology, law.invention, Randomized controlled trial, law, Internal medicine, Internal Medicine, medicine, Immunology and Allergy, Hepatology, business.industry, Incidence (epidemiology), cirrhosis, competing risk analysis, US, abdominal ultrasound, Hazard ratio, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Diseases of the digestive system. Gastroenterology, medicine.disease, HR, hazard ratio, Hepatocellular carcinoma, ALC, alcohol-related, Etiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, HCC, hepatocellular carcinoma, Research Article, alcoholic liver disease
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)., Graphical abstract, Highlights • Alcohol-related cirrhosis linked to the lowest incidence of HCC, the lowest overall survival and the highest incidence of decompensation. • Alcohol-related cirrhosis linked to fewer cases of early stage HCC, although tumour burden and Child-Pugh score were comparable across groups. • Patients with alcohol-related cirrhosis had worse survival after HCC diagnosis than those with virus-related cirrhosis. • The aetiology of cirrhosis had no impact on survival after HCC diagnosis following adjustment for other potential prognostic factors.
Published: 2021

15. Assessment of hepatic steatosis by controlled attenuation parameter using the M and XL probes:an individual patient data meta-analysis

Author: Emmanuel Tsochatzis, Olivier Chazouillères, Jeremy F. L. Cobbold, Stephan Baumeler, Sylvie Naveau, Thomas Karlas, Maja Thiele, Vincent Wai-Sun Wong, David Semela, Gabriel Perlemuter, Harshit Garg, Cristiane A. Villela-Nogueira, Magali Sasso, Marie Irles-Depe, Monica Lupsor-Platon, Peter J Eddowes, David Sheridan, Cosmin Sebastian Voican, Aleksander Krag, Johannes Wiegand, Shalimar, Sebastian Mueller, Philip N. Newsome, Victor de Ledinghen, Michael Allison, Sandeep Aggarwal, Quentin M. Anstee, Wah-Kheong Chan, David Petroff, A.C. Cardoso, Valentin Blank, and Grace Lai-Hung Wong
Subjects: Adult, Male, medicine.medical_specialty, Biopsy, MEDLINE, Severity of Illness Index, Body Mass Index, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Internal medicine, Severity of illness, medicine, Humans, Hepatology, Receiver operating characteristic, business.industry, Fatty liver, Gastroenterology, Middle Aged, medicine.disease, 3. Good health, Liver, ROC Curve, 030220 oncology & carcinogenesis, Meta-analysis, Area Under Curve, Elasticity Imaging Techniques, 030211 gastroenterology & hepatology, Female, Steatosis, business, Body mass index
Abstract: BACKGROUND: Diagnostic tools for liver disease can now include estimation of the grade of hepatic steatosis (S0 to S3). Controlled attenuation parameter (CAP) is a non-invasive method for assessing hepatic steatosis that has become available for patients who are obese (FibroScan XL probe), but a consensus has not yet been reached regarding cutoffs and its diagnostic performance. We aimed to assess diagnostic properties and identify relevant covariates with use of an individual patient data meta-analysis.METHODS: We did an individual patient data meta-analysis, in which we searched PubMed and Web of Science for studies published from database inception until April 30, 2019. Studies reporting original biopsy-controlled data of CAP for non-invasive grading of steatosis were eligible. Probe recommendation was based on automated selection, manual assessment of skin-to-liver-capsule distance, and a body-mass index (BMI) criterion. Receiver operating characteristic methods and mixed models were used to assess diagnostic properties and covariates. Patients with non-alcoholic fatty liver disease (NAFLD) were analysed separately because they are the predominant patient group when using the XL probe. This study is registered with PROSPERO, CRD42018099284.FINDINGS: 16 studies reported histology-controlled CAP including the XL probe, and individual data from 13 papers and 2346 patients were included. Patients with a mean age of 46·5 years (SD 14·5) were recruited from 20 centres in nine countries. 2283 patients had data for BMI; 673 (29%) were normal weight (BMI INTERPRETATION: CAP cutoffs varied according to cause, and can effectively recognise significant steatosis in patients with viral hepatitis. CAP cannot grade steatosis in patients with NAFLD adequately, but its value in a NAFLD screening setting needs to be studied, ideally with methods beyond the traditional histological reference standard.FUNDING: The German Federal Ministry of Education and Research and Echosens.
Published: 2021

16. Two-dimensional shear wave elastography predicts survival in advanced chronic liver disease

Author: Maximilian J. Brol, Maxime Ronot, Ioan Sporea, Laurent Castera, David Bauer, Rongqin Zheng, Renata Senkerikova, Ida Tjesic Drinkovic, Alina Popescu, Wenyi Gu, Benedikt Simbrunner, Thomas Vanwolleghem, Ditlev Nytoft Rasmussen, Johannes Chang, Luisa Vonghia, Martin Schulz, Christian P. Strassburg, Thomas Reiberger, Stanislas Pol, Cristina Margini, Sanda Mustapic, Maja Thiele, Xue Lu, Chrisitan Jansen, Maria Kjærgaard, Ivica Grgurević, Michael Praktiknjo, Olivier Guillaud, Halima Gottfriedová, Jérôme Boursier, Sven Francque, Mireen Friedrich-Rust, Valérie Vilgrain, Jonel Trebicka, Aymeric Guibal, Philip G. Ferstl, Filipe Andrade, Victor de Ledinghen, Christophe Cassinotto, Jérôme Dumortier, Annalisa Berzigotti, Stefan Zeuzem, Frank Erhard Uschner, Wen-Ping Wang, Christophe Aubé, Camille Vassord, Pierre-Emmanuel Rautou, Georg Semmler, Aleksander Krag, Grifols Chair, Partenaires INRAE, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Department of Internal Medicine, Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), and Hospices Civils de Lyon (HCL)
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, liver cirrhosis, [SDV]Life Sciences [q-bio], 610 Medicine & health, Chronic liver disease, clinical decision making, 03 medical and health sciences, 0302 clinical medicine, Model for End-Stage Liver Disease, Predictive Value of Tests, Internal medicine, Risk of mortality, Humans, Medicine, Decompensation, Retrospective Studies, business.industry, Liver Diseases, liver failure, Gastroenterology, chronic liver disease, portal hypertension, Middle Aged, medicine.disease, Survival Rate, 030104 developmental biology, ROC Curve, Chronic Disease, Cohort, Cardiology, Elasticity Imaging Techniques, Portal hypertension, Female, 030211 gastroenterology & hepatology, Human medicine, business, Transient elastography, Algorithms, Cohort study
Abstract: ObjectiveLiver stiffness measurement (LSM) is a tool used to screen for significant fibrosis and portal hypertension. The aim of this retrospective multicentre study was to develop an easy tool using LSM for clinical outcomes in advanced chronic liver disease (ACLD) patients.DesignThis international multicentre cohort study included a derivation ACLD patient cohort with valid two-dimensional shear wave elastography (2D-SWE) results. Clinical and laboratory parameters at baseline and during follow-up were recorded. LSM by transient elastography (TE) was also recorded if available. The primary outcome was overall mortality. The secondary outcome was the development of first/further decompensation.ResultsAfter screening 2148 patients (16 centres), 1827 patients (55 years, 62.4% men) were included in the 2D-SWE cohort, with median liver SWE (L-SWE) 11.8 kPa and a model for end stage liver disease (MELD) score of 8. Combination of MELD score and L-SWE predict independently of mortality (AUC 0.8). L-SWE cut-off at ≥20 kPa combined with MELD ≥10 could stratify the risk of mortality and first/further decompensation in ACLD patients. The 2-year mortality and decompensation rates were 36.9% and 61.8%, respectively, in the 305 (18.3%) high-risk patients (with L-SWE ≥20 kPa and MELD ≥10), while in the 944 (56.6%) low-risk patients, these were 1.1% and 3.5%, respectively. Importantly, this M10LS20 algorithm was validated by TE-based LSM and in an additional cohort of 119 patients with valid point shear SWE-LSM.ConclusionThe M10LS20 algorithm allows risk stratification of patients with ACLD. Patients with L-SWE ≥20 kPa and MELD ≥10 should be followed closely and receive intensified care, while patients with low risk may be managed at longer intervals.
Published: 2021

17. Molecular profiling and risk classification of patients with myeloproliferative neoplasms and splanchnic vein thromboses

Author: Christophe Bureau, Bruno Cassinat, Juliette Soret-Dulphy, Odile Goria, Aurélie Plessier, Dominique Valla, Barbara Mora, Victor de Ledinghen, Nabih Maslah, Emmanuelle Verger, Stéphane Giraudier, Pierre-Emmanuel Rautou, Francesco Passamonti, Jean-Jacques Kiladjian, Claudia Siracusa, Pierre-Edouard Debureaux, and Isabelle Ollivier-Hourman
Subjects: Adult, Male, medicine.medical_specialty, Clinical Trials and Observations, Population, Polycythemia vera, Internal medicine, medicine, Humans, education, Myelofibrosis, Polycythemia Vera, Retrospective Studies, Venous Thrombosis, education.field_of_study, Acute leukemia, Myeloproliferative Disorders, business.industry, food and beverages, Retrospective cohort study, Hematology, Odds ratio, medicine.disease, Thrombosis, Primary Myelofibrosis, Cohort, Female, business
Abstract: Myeloproliferative neoplasms (MPNs) are the most frequent underlying causes of splanchnic vein thromboses (SVTs). MPN patients with SVTs (MPN-SVT) often have a unique presentation including younger age, female predominance, and low Janus kinase 2 (JAK2) mutation allele burden. This study aimed at identifying risk factors for adverse hematologic outcomes in MPN-SVT patients. We performed a retrospective study of a fully characterized cohort of MPN-SVT patients. The primary outcome was the incidence of evolution to myelofibrosis, acute leukemia, or death. Eighty patients were included in the testing cohort. Median follow-up was 11 years. Most of the patients were women with a mean age of 42 years and a diagnosis of polycythemia vera. The primary outcome was met in 13% of the patients and was associated with a JAK2V617F allele burden ≥50% (odds ratio [OR], 14.7) and presence of additional mutations in genes affecting chromatin/spliceosome (OR, 9). We identified high-risk patients (29% of the cohort) as those harboring at least 1 molecular risk factor: JAK2-mutant allele burden ≥50%, presence of chromatin/spliceosome/TP53 mutation. High-risk patients had worse event-free survival (81% vs 100%; P = .001) and overall survival at 10 years (89% vs 100%; P = .01) than low-risk patients. These results were confirmed in an independent validation cohort of 30 MPN-SVT patients. In conclusion, molecular profiling identified MPN-SVT patients with dismal outcome. In this high-risk population, a disease-modifying therapy should be taken into consideration to minimize the probability of transformation.
Published: 2020

18. Eight Weeks of Treatment With Glecaprevir/Pibrentasvir Is Safe and Efficacious in an Integrated Analysis of Treatment-Naïve Patients With Hepatitis C Virus Infection

Author: Julio A. Gutierrez, Eli Zuckerman, Stanley N. Cohen, Lino Rodrigues, Michael Gschwantler, Frederik Nevens, Ana Gabriela Pires dos Santos, Douglas E. Dylla, Victor de Ledinghen, Massimo Puoti, Andrew J. Muir, Jihad Slim, Linda M Fredrick, Florin Caruntu, John F. Dillon, and Samuel H. Sigal
Subjects: Cyclopropanes, medicine.medical_specialty, Cirrhosis, Aminoisobutyric Acids, Pyrrolidines, Genotype, Proline, Lactams, Macrocyclic, Population, Hepacivirus, liver, Gastroenterology, Antiviral Agents, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Leucine, Internal medicine, Quinoxalines, medicine, Humans, education, Adverse effect, DAA, pangenotypic, education.field_of_study, Sulfonamides, Intention-to-treat analysis, Hepatology, business.industry, fibrosis, Glecaprevir, Hepatitis C, Chronic, Middle Aged, medicine.disease, Hepatitis C, Pibrentasvir, Discontinuation, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Benzimidazoles, business
Abstract: BACKGROUND & AIMS: The direct-acting antiviral combination glecaprevir/pibrentasvir has been approved by the Food and Drug Administration for 8 weeks of treatment in treatment-naïve patients with hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis. We performed an integrated analysis of data from trials to evaluate the overall efficacy and safety of 8 weeks of glecaprevir/pibrentasvir in treatment-naïve patients without cirrhosis or with compensated cirrhosis. METHODS: We pooled data from 8 phase 2 or phase 3 trials of treatment-naïve patients with HCV genotype 1 to 6 infections, without cirrhosis or with compensated cirrhosis, who received 8 weeks of glecaprevir/pibrentasvir. RESULTS: Of 1248 patients, 343 (27%) had cirrhosis. Most patients were white (80%) and had HCV genotype 1 infection (47%) or genotype 3 infection (22%); the median age was 54 years. Overall rates of sustained virologic response at post-treatment week 12 were 97.6% (1218 of 1248) in the intention to treat (ITT) and 99.3% (1218 of 1226) in the modified ITT populations. When we excluded patients with genotype 3 infections with compensated cirrhosis (consistent with the European label), rates of sustained virologic response at post-treatment week 12 were 97.6% in the ITT and 99.4% in the modified ITT populations. Eight virologic failures (7 in patients without cirrhosis and 1 in a patient with cirrhosis) occurred in the ITT population. Virologic failure was not associated with markers of advanced liver disease or populations of interest (current alcohol use, opioid substitution therapy, history of injection-drug use, and severe renal impairment). Treatment-emergent adverse events (AEs) occurred in 58% of patients. The most frequent AEs (>10%) were headache (12%) and fatigue (12%). Serious AEs and AEs that led to glecaprevir/pibrentasvir discontinuation were reported in 2% and less than 1% of patients, respectively. CONCLUSIONS: In a pooled analysis of data from 8 trials, we found that 8 weeks of treatment with glecaprevir/pibrentasvir is efficacious and well tolerated in treatment-naïve patients with HCV genotype 1 to 6 infections, with or without cirrhosis. ispartof: CLINICAL GASTROENTEROLOGY AND HEPATOLOGY vol:18 issue:11 pages:2544-+ ispartof: location:United States status: published
Published: 2020

19. Impact of Preexisting Inflammatory Bowel Disease on the Outcome of Liver Transplantation for Primary Sclerosing Cholangitis

Author: Laurence Chiche, Victor de Ledinghen, Marie Irles-Depe, Pauline Houssel-Debry, Martine Neau-Cransac, Sébastien Dharancy, Olivier Boillot, Jérôme Dumortier, Christophe Laurent, David Laharie, and Stéphanie Roullet
Subjects: Adult, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, Cholangitis, Sclerosing, Azathioprine, 030230 surgery, Liver transplantation, Lower risk, digestive system, Gastroenterology, Inflammatory bowel disease, Primary sclerosing cholangitis, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Medicine, Humans, Retrospective Studies, Transplantation, Hepatology, business.industry, Incidence (epidemiology), Odds ratio, medicine.disease, Inflammatory Bowel Diseases, digestive system diseases, Liver Transplantation, 030211 gastroenterology & hepatology, Surgery, business, medicine.drug
Abstract: Approximately 80% of patients with primary sclerosing cholangitis (PSC) also have inflammatory bowel disease (IBD). The effect of IBD on the outcomes of liver transplantation (LT) for PSC is unclear. We retrospectively collected data from adults who underwent LT for PSC from 1989 to 2017 in four French LT centers. We compared the rates of patient and graft survivals and of complications after LT. Among 87 patients, 52 (60%) had pre-existing IBD. Excluding those who died within the first 3 months, the 10-year patient survival and graft survival rates were 92.6% (95% confidence interval [CI] 84.3-100) and 77.1% (95% CI 53.8-85.3) in the PSC with IBD (PSC-IBD) group and 97.1% (95% CI 91.4-100) (p = 0.44) and 83.2% (95% CI 69.6-96.9) (p = 0.43) in the isolated PSC group, respectively. Exposure to azathioprine after LT was significantly associated with mortality (odds ratio [OR] 15.55 [95% CI 1.31-184.0], p = 0.03), whereas exposure to mycophenolate mofetil was associated with improved survival (OR 0.17 [95% CI 0.04-0.82], p = 0.03), which may be an era effect. Exposure to cyclosporine was associated with graft loss, albeit at borderline significance: OR 3.60 [95% CI 0.96-13.42] (p = 0.06). The rate of recurrent PSC was 21% in the PSC-IBD group and 11% in the isolated PSC group (p = 0.24). The incidence of severe infection was 125 per 1000 person-years in both groups. Exposure to mycophenolate mofetil was associated with a lower risk of infection (OR 0.26 [95% CI 0.08-0.85] p = 0.03). The presence of IBD was associated with cytomegalovirus infection (OR 3.24 [95% CI 1.05-9.98], p = 0.04). The crude incidence of skin cancer was higher in the PSC-IBD group (p = 0.06). One case of colorectal cancer occurred in a patient with IBD. CONCLUSION: IBD prior to LT for PSC may not affect patient or transplant survival but may increase the risk of cytomegalovirus infection.
Published: 2020

20. Origin, HDV genotype and persistent viremia determine outcome and treatment response in patients with chronic hepatitis delta

Author: Isabelle Rosa, Fabien Zoulim, Vincent Thibault, Christophe Hézode, Victor de Ledinghen, Thierry Poynard, Xavier Causse, Sophie Hillaire, Hélène Fontaine, Richard Layese, Jérôme Gournay, Nathalie Ganne, Ghassan Riachi, Emmanuel Gordien, Eric Nguyen-Khac, Sophie Metivier, Olivier Chazouillères, Dominique Roulot, Roland Landman, Paul Calès, Dominique Salmon, Pierre Nahon, Cécile Goujard, Zahia Ben-Abdesselam, Ségolène Brichler, H. Labadie, Jean-François Cadranel, Caroline Lascoux-Combe, Véronique Loustaud-Ratti, Bruno Roche, P. Sellier, Corinne Castelnau, Frédéric Le Gal, Philippe Mathurin, Dominique Guyader, Julie Bottero, Françoise Roudot-Thoraval, Laurent Alric, François Habersetzer, Caroline Scholtes, Jean-Didier Grangé, Sylvie Naveau, 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), Hôpital Avicenne [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), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 ), Hospices Civils de Lyon (HCL), Hôpital Paul Brousse, Hôpital Beaujon [AP-HP], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Jean Verdier [AP-HP], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Pontchaillou [Rennes], 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), Agence Nationale de Recherches sur le Sida et les Hépatites Virales, France REcherche Nord & sud Sida-HIV Hépatites, 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 ), 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), and Jonchère, Laurent
Subjects: Adult, Liver Cirrhosis, Male, 0301 basic medicine, medicine.medical_specialty, Carcinoma, Hepatocellular, Cirrhosis, Hepatitis D, Chronic, viruses, African origin, HDV persistent viremia, [SDV]Life Sciences [q-bio], Chronic liver disease, Severity of Illness Index, HDV genotype, 03 medical and health sciences, 0302 clinical medicine, Residence Characteristics, Internal medicine, medicine, Humans, Decompensation, Viremia, Retrospective Studies, Deltavir study, Liver infection, Hepatology, business.industry, Liver Neoplasms, virus diseases, Retrospective cohort study, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Viral Load, biochemical phenomena, metabolism, and nutrition, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Cohort, Female, 030211 gastroenterology & hepatology, France, Interferons, Hepatitis Delta Virus, Viral hepatitis, business, Viral load, Liver outcome
Abstract: International audience; Background & aims: HDV infection causes severe chronic liver disease in individuals infected with HBV. However, the factors associated with poor prognosis are largely unknown. Thus, we aimed to identify prognostic factors in patients with HDV infection.Methods: The French National Reference Centre for HDV performed a nationwide retrospective study on 1,112 HDV-infected patients, collecting epidemiological, clinical, virological and histological data from the initial referral to the last recorded follow-up.Results: The median age of our cohort was 36.5 (29.9-43.2) years and 68.6% of our cohort were male. Most patients whose birthplace was known were immigrants from sub-Saharan Africa (52.5%), southern and eastern Europe (21.3%), northern Africa and the Middle East (6.2%), Asia (5.9%) and South America (0.3%). Only 150 patients (13.8%) were French native. HDV load was positive in 659 of 748 tested patients (88.1%). HDV-1 was predominant (75.9%), followed by sub-Saharan genotypes: HDV-5 (17.6%), HDV-7 (2.9%), HDV-6 (1.8%) and HDV-8 (1.6%). At referral, 312 patients (28.2%) had cirrhosis, half having experienced at least 1 episode of hepatic decompensation. Cirrhosis was significantly less frequent in African than in European patients regardless of HDV genotype. At the end of follow-up (median 3.0 [0.8-7.2] years), 48.8% of the patients had developed cirrhosis, 24.2% had ≥1 episode(s) of decompensation and 9.2% had hepatocellular carcinoma. European HDV-1 and African HDV-5 patients were more at risk of developing cirrhosis. Persistent replicative HDV infection was associated with decompensation, hepatocellular carcinoma and death. African patients displayed better response to interferon therapy than non-African patients (46.4% vs. 29.1%, p
Published: 2020

21. Sofosbuvir-Daclatasvir Is Suboptimal in Patients with Genotype 2 Chronic Hepatitis C Infection: Real-life Experience from the HEPATHER ANRS CO22 Cohort

Author: Dominique Larrey, Albert Tran, Fabrice Carrat, Didier Samuel, Stéphane Chevaliez, Fabien Zoulim, Hélène Fontaine, Jean-Michel Pawlotsky, Olivier Chazouillères, Jean-Pierre Bronowicki, Céline Dorival, Afef, Patrick Marcellin, Clovis Lusivika-Nzinga, Stanislas Pol, Victor de Ledinghen, Sophie Metivier, Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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], 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 de Chirurgie Digestive / Centre de Transplantation Hépatique [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), 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 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), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, 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), 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 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), Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], CHU Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Gestionnaire, Hal Sorbonne Université
Subjects: medicine.medical_specialty, Pyrrolidines, Daclatasvir, Genotype, Sofosbuvir, [SDV]Life Sciences [q-bio], Hepacivirus, Antiviral Agents, chemistry.chemical_compound, Virology, Internal medicine, medicine, Humans, Prospective Studies, Adverse effect, Hepatitis, Hepatology, business.industry, Ribavirin, Imidazoles, virus diseases, Valine, Hepatitis C, Hepatitis C, Chronic, medicine.disease, digestive system diseases, Discontinuation, [SDV] Life Sciences [q-bio], Regimen, Infectious Diseases, chemistry, Drug Therapy, Combination, Carbamates, business, medicine.drug
Abstract: Sofosbuvir plus daclatasvir with or without ribavirin has demonstrated a high efficacy and an acceptable safety profile in clinical trials of patients infected with genotype 2 hepatitis Cvirus (HCV); however, there are currently no real-world data available for this regimen. To evaluate the real-life safety and efficacy of sofosbuvir/daclatasvir with or without ribavirin in genotype 2 HCV patients in the French cohort ANRS CO22 HEPATHER(NCT01953458). In this ongoing, national, multicentre, prospective, observational study, we observed patients with HCV genotype 2 infection who initiated treatment with sofosbuvir (400 mg/d) plus daclatasvir with or without ribavirin (1-1.2 g/d). Patients were divided into two treatment groups: sofosbuvir/daclatasvir with or without ribavirin (12 weeks/24 weeks). The primary end point was a sustained virological response at week 12 following the end of therapy. Overall, 88% and 91% of patients achieved a sustained virological response following 12 and 24 weeks of treatment with sofosbuvir/daclatasvir with or without ribavirin, respectively. The most common adverse events were asthenia (29%), headache (15%) and fatigue (20%), and ribavirin addition was associated with a higher rate of adverse events and treatment discontinuation. Sofosbuvir/daclatasvir with or without ribavirin was associated with lower rates of sustained virological response in the real-life setting compared with the clinical setting and demonstrated suboptimal efficacy for the treatment of patients with genotype 2 chronic HCV.
Published: 2020

22. Fibrosis Assessment in Patients with NAFLD

Author: Victor de Ledinghen
Subjects: medicine.medical_specialty, Alcoholic liver disease, Cirrhosis, medicine.diagnostic_test, business.industry, Liver fibrosis, nutritional and metabolic diseases, Chronic liver disease, medicine.disease, digestive system, Gastroenterology, digestive system diseases, Fibrosis, Internal medicine, Liver biopsy, Nonalcoholic fatty liver disease, medicine, Transient elastography, business
Abstract: Nonalcoholic fatty liver disease (NAFLD) is becoming, next to alcoholic liver disease, the most common cause of chronic liver disease in the industrialized countries. Due to this epidemic proportion of individuals with NAFLD worldwide, liver biopsy is impractical in all patients and noninvasive assessment for the diagnosis of liver fibrosis related to NAFLD is needed. In this review, we summarize the current state of the noninvasive assessment of liver fibrosis in NAFLD and its usefulness for the evaluation of prognosis and follow-up of patients.
Published: 2020

23. French Patients with Hepatitis C Treated with Direct-Acting Antiviral Combinations: The Effect on Patient-Reported Outcomes

Author: Zobair M. Younossi, Marc Bourliere, Linda Henry, Christophe Hézode, T. Asselah, Philippe Mathurin, Victor de Ledinghen, Maria Stepanova, and Patrice Cacoub
Subjects: Adult, Male, Ledipasvir, medicine.medical_specialty, Sofosbuvir, Voxilaprevir, Chronic liver disease, Placebo, Antiviral Agents, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Humans, Multicenter Studies as Topic, Medicine, Patient Reported Outcome Measures, 030212 general & internal medicine, business.industry, Health Policy, Ribavirin, Public Health, Environmental and Occupational Health, Hepatitis C, Middle Aged, medicine.disease, Clinical trial, Treatment Outcome, Clinical Trials, Phase III as Topic, chemistry, Quality of Life, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, France, business, medicine.drug
Abstract: In addition to high efficacy, new anti-hepatitis C virus (HCV) regimens improve patient-reported outcomes (PROs), which must be considered by policymakers in different countries when deciding upon treatment coverage.To assess PROs of French patients with HCV treated with different antiviral regimens.French patients with HCV from 11 clinical trials were included. PROs were measured before, during, and after treatment (Short Form-36 version 2, Functional Assessment of Chronic Illness Therapy-Fatigue, Chronic Liver Disease Questionnaire-HCV, and Work Productivity and Activity Index: Specific Health Problem).A total of 931 subjects (age 54 ± 10 years, 60.3% males, 55% employed, 33.5% cirrhotic, 50% treatment-naive, and 45.6% genotype 1) were treated with a combination of interferon, ribavirin, and sofosbuvir (IFN + RBV + SOF) (N = 11; excluded from comparisons), SOF/RBV ± ledipasvir (LDV) (N = 202), IFN/RBV-free (LDV/SOF, SOF/velpatasvir, or SOF/velpatasvir/voxilaprevir) (N = 594), or placebo (N = 124). The sustained virologic response 12 (SVR-12) rates were 87.1% for IFN-free RBV-containing regimens, 97.6% for IFN/RBV-free regimens, and 0% for placebo. Baseline PRO scores were not different across the treatment groups (all P0.10). At the end of treatment, patients treated with IFN-free SOF/RBV ± LDV experienced moderate declines in their PRO scores (up to -7.9% of a PRO range size; P0.05), and placebo-treated group did not have significant changes in their PROs (P0.05). In contrast, the IFN/RBV-free group experienced significant on-treatment improvement in most PROs (up to +7.9%; P0.05). Despite those on-treatment differences, most PROs improved with SVR-12 and SVR-24 regardless of the regimen. In comparison with matched controls from the United States treated with the same regimens, French subjects had lower baseline PROs but similar or greater post-SVR PRO improvements.The use of IFN- and RBV-free regimens leads to significant PRO improvement during treatment and after SVR in French patients with HCV.
Published: 2018

24. 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

25. Diagnostic performance of a new noninvasive test for nonalcoholic steatohepatitis using a simplified histological reference

Author: Yen Ngo, Raluca Pais, Olivier Deckmyn, Wassil Merrouche, Thierry Poynard, Frédéric Charlotte, Mona Munteanu, Victor de Ledinghen, Philippe Mathurin, Vlad Ratziu, and Hugo Perazzo
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Biopsy, Sensitivity and Specificity, Severity of Illness Index, Gastroenterology, Random Allocation, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Internal medicine, Nonalcoholic fatty liver disease, medicine, Humans, Prospective Studies, Prospective cohort study, Aged, Hepatology, medicine.diagnostic_test, Receiver operating characteristic, business.industry, FibroTest, Reproducibility of Results, Middle Aged, medicine.disease, Confidence interval, 030104 developmental biology, Liver, Female, 030211 gastroenterology & hepatology, France, Steatosis, business, Biomarkers
Abstract: BACKGROUND One of the unmet needs in patients with metabolic risks is the prediction of metabolic liver disease (MLD) by noninvasive tests (NITs). OBJECTIVE The primary aim of this study was to construct a new quantitative test for the diagnosis of nonalcoholic steatohepatitis (NASH) using a simplified histological definition. PATIENTS AND METHODS As a reference, we used a simplified histological definition of NASH derived from the FLIP-CRN-definition that does not require the presence of steatosis and the presence of both lobular inflammation and ballooning. We analyzed 1081 patients from two prospective cohorts at risk of MLD who had biopsies and contemporaneous blood samples. These patients were divided randomly into a training group (n=541) and a control group (n=540) for internal validation. The new test was compared with standard tests, and applied in two large populations at risk of MLD. RESULTS Out of 1081 patients with biopsy, 39 (3.6%) cases with significant inflammatory activity or fibrosis (A2orF2) were missed by the current histological definitions. The combination of 11 parameters permitted to construct a test (NIT-NASHs) predicting NASH with an area under the receiver operating characteristic curve (AUROC) of 0.773 (95% confidence interval: 0.730-0.810), confirmed in the control group 0.814 (0.774-0.847). The AUROCs of NIT-NASHs were higher (all P
Published: 2018

26. S01-3CONTROLLED ATTENUATION PARAMETER FOR THE ASSESSMENT OF ALCOHOLIC HEPATIC STEATOSIS: BIOPSY-CONTROLLED DIAGNOSTIC ACCURACY AND ROLE OF DETOXIFICATION

Author: Sebastian Mueller, Felix Piecha, Maja Thiele, Beate K. Straub, Vanessa Rausch, Sönke Detlefsen, Monica Lupsor-Platon, Aleksander Krag, Bjørn Stæhr Madsen, Helmut K. Seitz, Johannes Mueller, Victor de Ledinghen, and Gabriele Fluhr
Subjects: medicine.medical_specialty, medicine.diagnostic_test, business.industry, Internal medicine, Detoxification, Biopsy, medicine, Diagnostic accuracy, General Medicine, Steatosis, medicine.disease, business, Gastroenterology
Published: 2017

27. Baseline and Post-Treatment Hepatitis C NS5A Resistance in Relapsed Patients from a Multicentric Real-Life Cohort

Author: Philippe Halfon, Jacques Izopet, Pascale Trimoulet, Caroline Scholtes, Sofiane Mohamed, Denis Ouzan, Laurent Chiche, Victor de Ledinghen, Hacène Khiri, Marc Bourlière, M.A. Thelu, Sophie Metivier, Guillaume Penaranda, Anne Plauzolles, Laurent Alric, Vincent Leroy, Fabien Zoulim, Sylvie Larrat, Florence Abravanel, ALPHABIO - Laboratoire de biologie médicale, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service d'Hépatologie et de Gastroentérologie [Lyon], Hospices Civils de Lyon (HCL), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Gastro-entérologie - Hépatologie [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Hôpital Michallon, Institut Arnault Tzanck, Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, 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 de médecine interne [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Hôpital Européen [Fondation Ambroise Paré - Marseille], Centre Hospitalier Universitaire de Lyon (CHU Lyon), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Bordeaux [Bordeaux], 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), Hôpital Haut-Lévêque [CHU Bordeaux], Hôpital Saint-Joseph [Marseille], 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-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon], 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), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), 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-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, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire de Virologie [CHU Purpan, Toulouse], Institut Fédératif de Biologie (IFB) - Hôpital Purpan, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT)
Subjects: Male, 0301 basic medicine, DNA Mutational Analysis, Viral Nonstructural Proteins / genetics, Drug Resistance, Hepacivirus, Drug resistance, Viral Nonstructural Proteins, Virological response, Viral Nonstructural Proteins / antagonists & inhibitors, 0302 clinical medicine, Medicine, Pharmacology (medical), Viral, Treatment Failure, Hepatitis C, Viral Load, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 3. Good health, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Treatment Outcome, Infectious Diseases, Antiviral Agents / pharmacology, Cohort, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, Viral load, Hepacivirus / genetics, medicine.medical_specialty, Genotype, Antiviral Agents / therapeutic use, Antiviral Agents, 03 medical and health sciences, Pharmacotherapy, Drug Therapy, Internal medicine, Drug Resistance, Viral, Humans, NS5A, Pharmacology, business.industry, medicine.disease, 030104 developmental biology, Hepatitis C / virology, Hepacivirus / drug effects, Post treatment, Hepatitis C / drug therapy, business
Abstract: Background Recent data have suggested that failure to achieve sustained virological response with direct-acting antiviral therapy is usually due to relapse and is primarily associated with the emergence of resistance-associated substitutions. The aim of this study was to investigate the prevalence and characterization of non-structural-5A resistance-associated substitutions in patients infected with HCV genotypes 1, 3 and 4 treated by direct-acting antiviral therapy, including anti-non-structural-5A, and to characterize the pre-existing resistance-associated substitutions in subjects treated with anti-non-structural-5A inhibitors. Methods From January 2014 to March 2016, 2,995 patients infected with HCV genotypes 1, 3 and 4 were exposed to non-structural-5A inhibitors. Sequencing results at the time of virological failure were available for 61 patients; sequencing at baseline was available for 35 of these patients. Results Among the 35 patients with sequencing results available at baseline, 15 had no resistance-associated substitution, 16 had only one resistance-associated substitution, and 4 had more than one resistance-associated substitution. Resistance-associated substitutions were harbored in 57% of the sequences in the non-structural-5A region. Among the 61 patients sequenced at virological failure, 50 (82%) patients presented at least one resistance-associated substitutions inducing a high level of resistance to non-structural-5A inhibitors (>10-fold resistance). Conclusions This pooled analysis suggests that non-structural-5A resistance-associated substitutions screening should be recommended when considering retreatment with a non-structural-5A inhibitor regimen in patients who have previously experienced failed non-structural-5A treatment.
Published: 2017

28. Hepatitis C virus prevalence and level of intervention required to achieve the WHO targets for elimination in the European Union by 2030: a modelling study

Author: Wolfgang Vogel, M. Blachier, Lelia Thornton, Wim Laleman, Ieva Tolmane, Antonio Craxì, Mojca Matičič, Hans Van Vlierberghe, Christoph Sarrazin, Laura Harcouet, Joël Mossong, Ilias Gountas, Matthew E. Cramp, Devin Razavi-Shearer, Soo Aleman, Lyudmila Mateva, Ann-Sofi Duberg, Vratislav Nemecek, Jordan Genov, Michael Manns, Anne Øvrehus, Irena Hrstić, Kimberly Murphy, Stefano Vella, Krzysztof Tomasiewicz, Francesco Negro, Nina Weis, Antonio Javier Blasco, Agita Jeruma, Karolin Falconer, Danute Speiciene, Jonas Valantinas, Jose Luis Calleja, Jan Sperl, Gabor Horvath, Filipe Calinas, Peter Jarcuska, Jerneja Videčnik-Zorman, Ivan Schréter, Kathryn Razavi-Shearer, Christophe Moreno, Sergeja Gregorčič, Angelos Hatzakis, Pierre Van Damme, Riina Salupere, Massimo Colombo, Robert J. de Knegt, Peter J Smit, Dijana Nonkovic, Daniela K van Santen, Waldemar Halota, Rui Sarmento-Castro, Jean-Michel Delile, Suzanne Norris, Vana Sypsa, Robert Flisiak, Carole Seguin-Devaux, Martin Lagging, Liana Gheorghe, Mihály Makara, Javier García-Samaniego, Christophe Hézode, Jennifer Kieran, Marian Oltman, Peter Stärkel, Victor de Ledinghen, Pablo Lázaro, Stefan Zeuzem, E. A. Croes, Patrick Hoffmann, Matti Maimets, Francesco Saverio Mennini, Kostas Athanasakis, Chris Estes, Stephen D. Ryder, Sarah Robbins, Françoise Roudot-Thoraval, Martin Kåberg, Kaarlo Simojoki, Sona Frankova, Adrian Goldis, Marietta Simonova, Kyriakos Souliotis, Ken Pasini, Homie Razavi, Rui Tato Marinho, Sarah Blach, Pavol Kristian, Rumiana Mitova, Loreta A. Kondili, Maria Buti, Helen Nde, Boris Lukšić, Henrik Krarup, Dominique Vandijck, Henk W. Reesink, David A. M. C. van de Vijver, Iskren Kotzev, Jessie Gunter, Adriaan J. van der Meer, Martti Färkkilä, Baiba Rozentale, Perttu Arkkila, Krasimir Antonov, Jan Gerstoft, Béla Hunyady, Peer Brehm Christensen, Ivane Gamkrelidze, Valentina Liakina, Michael Gschwantler, Deian Jelev, Tatjana Reic, George V. Papatheodoridis, Jonathan Schmelzer, Daniel Struck, Gastroenterology & Hepatology, Razavi, Homie, Robbins, Sarah, Zeuzem, Stefan, Negro, Francesco, Buti, Maria, Duberg, Ann-Sofi, Roudot-Thoraval, FranÃ§oise, Craxi, Antonio, Manns, Michael, Marinho, Rui T, Hunyady, Bela, Colombo, Massimo, Aleman, Soo, Antonov, Krasimir, Arkkila, Perttu, Athanasakis, Kosta, Blach, Sarah, Blachier, Martin, Blasco, Antonio J, Calinas, Filipe, Calleja, Jose L, Christensen, Peer B, Cramp, Matthew E, Croes, Esther, de Knegt, Robert J, de Ledinghen, Victor, Delile, Jean-Michel, Estes, Chri, Falconer, Karolin, FÃ¤rkkilÃ¤, Martti, Flisiak, Robert, Frankova, Sona, Gamkrelidze, Ivane, GarcÃa-Samaniego, Javier, Genov, Jordan, Gerstoft, Jan, Gheorghe, Liana, Goldis, Adrian, Gountas, Ilia, GregorÄ iÄ , Sergeja, Gschwantler, Michael, Gunter, Jessie, Halota, Waldemar, Harcouet, Laura, HÃ©zode, Christophe, Hoffmann, Patrick, Horvath, Gabor, Hrstic, Irena, JarÄ uÅ¡ka, Peter, Jelev, Deian, Jeruma, Agita, KÃ¥berg, Martin, Kieran, Jennifer, Kondili, Loreta A, Kotzev, Iskren, Krarup, Henrik, Kristian, Pavol, Lagging, Martin, Laleman, Wim, LÃ¡zaro, Pablo, Liakina, Valentina, LukÅ¡iÄ , Bori, Maimets, Matti, Makara, MihÃ¡ly, Mateva, Lyudmila, Maticic, Mojca, Mennini, Francesco S, Mitova, Rumiana, Moreno, Christophe, Mossong, Joel, Murphy, Kimberly, Nde, Helen, Nemecek, Vratislav, Nonkovic, Dijana, Norris, Suzanne, Oltman, Marian, Ã vrehus, Anne L H, Papatheodoridis, George, Pasini, Ken, Razavi-Shearer, Devin, Razavi-Shearer, Kathryn, Reesink, Henk W, Reic, Tatjana, Rozentale, Baiba, Ryder, Stephen D, Salupere, Riina, Sarmento-Castro, Rui, Sarrazin, Christoph, Schmelzer, Jonathan D, SchrÃ©ter, Ivan, Seguin-Devaux, Carole, Simojoki, Kaarlo, Simonova, Marietta, Smit, Peter J, Souliotis, Kyriako, Speiciene, Danute, Sperl, Jan, StÃ¤rkel, Peter, Struck, Daniel, Sypsa, Vana, Thornton, Lelia, Tolmane, Ieva, Tomasiewicz, Krzysztof, Valantinas, Jona, Van Damme, Pierre, van de Vijver, David, van der Meer, Adriaan J, van Santen, Daniela, Van Vlierberghe, Han, Vandijck, Dominique, Vella, Stefano, VideÄ nik-Zorman, Jerneja, Vogel, Wolfgang, Weis, Nina, Hatzakis, Angelos, European Union HCV Collaborators, and Faculteit Medische Wetenschappen/UMCG
Subjects: Pediatrics, ddc:616.07, medicine.disease_cause, 0302 clinical medicine, Cost of Illness, Epidemiology, Prevalence, EPIDEMIOLOGY, 030212 general & internal medicine, Settore SECS-P/01 - Economia Politica, CIRRHOSIS, media_common, ddc:616, Antiviral Agents/therapeutic use, education.field_of_study, INJECT DRUGS, Gastroenterology, HCV INFECTION, virus diseases, Hepatitis C, Emigration and Immigration, DISEASE BURDEN, Markov Chains, Emigration and Immigration/statistics & numerical data, 030211 gastroenterology & hepatology, Viral hepatitis, Modelling, Eradication, European Union, prevalence, COUNTRIES, medicine.medical_specialty, Hepatitis C virus, Population, UNITED-STATES, World Health Organization, Antiviral Agents, 03 medical and health sciences, SDG 3 - Good Health and Well-being, PEOPLE, Internal medicine, Intervention (counseling), medicine, Journal Article, media_common.cataloged_instance, Humans, Viremia, European union, Disease Eradication, education, Hepatitis C/diagnosis/drug therapy/epidemiology/prevention & control, Hepatology, business.industry, Viremia/diagnosis/drug therapy/epidemiology/prevention & control, medicine.disease, Virology, PREVENTION, digestive system diseases, Human medicine, VIRAL-HEPATITIS, business
Abstract: Background Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide. In the European Union (EU), treatment and cure of HCV with direct-acting antiviral therapies began in 2014. WHO targets are to achieve a 65% reduction in liver-related deaths, a 90% reduction of new viral hepatitis infections, and 90% of patients with viral hepatitis infections being diagnosed by 2030. This study assessed the prevalence of HCV in the EU and the level of intervention required to achieve WHO targets for HCV elimination. Methods We populated country Markov models for the 28 EU countries through a literature search of PubMed and Embase between Jan 1, 2000, and March 31, 2016, and a Delphi process to gain expert consensus and validate inputs. We aggregated country models to create a regional EU model. We used the EU model to forecast HCV disease progression (considering the effect of immigration) and developed a strategy to acehive WHO targets. We used weighted average sustained viral response rates and fibrosis restrictions to model the effect of current therapeutic guidelines. We used the EU model to forecast HCV disease progression (considering the effect of immigration) under current screening and therapeutic guidelines. Additionally, we back-calculated the total number of patients needing to be screened and treated to achieve WHO targets. Findings We estimated the number of viraemic HCV infections in 2015 to be 3â238â000 (95% uncertainty interval [UI] 2â106â000â3â795â000) of a total population of 509â868â000 in the EU, equating to a prevalence of viraemic HCV of 0Â·64% (95% UI 0Â·41â0Â·74). We estimated that 1â180â000 (95% UI 1â003â000â1â357â000) people were diagnosed with viraemia (36Â·4%), 150â000 (12â000â180â000) were treated (4Â·6% of the total infected population or 12Â·7% of the diagnosed population), 133â000 (106â000â160â000) were cured (4Â·1%), and 57â900 (43â900â67â300) were newly infected (1Â·8%) in 2015. Additionally, 30â400 (26â600â42â500) HCV-positive immigrants entered the EU. To achieve WHO targets, unrestricted treatment needs to increase from 150â000 patients in 2015 to 187â000 patients in 2025 and diagnosis needs to increase from 88â800 new cases annually in 2015 to 180â000 in 2025. Interpretation Given its advanced health-care infrastructure, the EU is uniquely poised to eliminate HCV; however, expansion of screening programmes is essential to increase treatment to achieve the WHO targets. A united effort, grounded in sound epidemiological evidence, will also be necessary. Funding Gilead Sciences.
Published: 2017

29. Hepatitis C virus infection impacts work productivity and fatigue: An epidemiologic real-life study

Author: Joseph Moussalli, Victor de Ledinghen, Dominique Larrey, Si Nafa Si Ahmed, Bertrand Hanslik, Denis Ouzan, and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Male, Quality of life, Work, medicine.medical_specialty, Health Status, Hepatitis C virus, [SDV]Life Sciences [q-bio], Specialties of internal medicine, Efficiency, Disease, medicine.disease_cause, Antiviral Agents, Severity of Illness Index, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pegylated interferon, Internal medicine, Humans, Medicine, Disease management (health), Tiredness, Fatigue, Aged, Retrospective Studies, Work productivity, Hepatology, business.industry, Incidence, Ribavirin, General Medicine, Hepatitis C, Chronic, Middle Aged, Prognosis, medicine.disease, Comorbidity, 3. Good health, Cross-Sectional Studies, RC581-951, chemistry, 030220 oncology & carcinogenesis, Active life impairment, Female, 030211 gastroenterology & hepatology, France, business, Follow-Up Studies, medicine.drug
Abstract: Introduction and Objective Hepatitis C virus (HCV) infection and treatment impact the patient's daily life and work productivity. Until recently, treatments were associated with side effects and insufficient virologic and hepatic results. This study evaluated fatigue, work productivity, and treatment modalities in patients with HCV infection. Materials and methods This cross-sectional, non-interventional, multicenter study was conducted in real-life settings between March and December 2015 at 109 sites in France. Results Data from 1269 patients were evaluable. The mean patient age was 55.8 ± 12.5 years; 53.3% (676) patients were male. A total of 80.1% (1015) of patients were Caucasian and 62.3% (791) had a genotype 1 infection, 34.2% (433) had at least one comorbidity and 15.6% (198) had ≥1 clinical sign/symptom. Illicit drug use was the main route of HCV transmission and accounted for 36.8% (466) of all infections. Fibrosis stage F0/F1 was reported in 41.4% (525) of patients. A majority of patients (60.4%, 764) had never been treated. In patients previously treated, 85.8% (430) received ribavirin and pegylated interferon and only 13.4% (67) direct-acting antivirals. The mean percent of global impairment due to health was highest (34.8 ± 30.9%) in patients 18–45 years of age. The prevalence of active employed patients with a total fatigue score ≥ its median value (45/160) was 38.6%. The mean percent work time missed due to health was 9.6 ± 23.6% for working patients of 18–45 years of age and 7.3 ± 21.8% for working patients of 45–65 years of age. The mean overall prevalence of employed patients with impairment due to health issues was 21.8 ± 26.8%. The prevalence of patients with a reduced work activity of ≥50% due to their health status was 32.1%. Conclusion These data reinforce the request for improved disease management in France, allowing patients with HCV infection to increase work productivity, reduce fatigue, and, hopefully, cure their disease.
Published: 2019

30. Performance of Simple Fibrosis Scores in Nonobese Patients With Nonalcoholic Fatty Liver Disease

Author: Janae Wentong Wai, Victor de Ledinghen, Wah-Kheong Chan, Charmaine Fu, Nik Raihan Nik Mustapha, Marie Irles, Sarah Shili, Sanjiv Mahadeva, Vincent Wai-Sun Wong, Juliette Foucher, Henry Lik-Yuen Chan, Anthony W.H. Chan, Grace Lai-Hung Wong, Brigitte Le Bail, Wassil Merrouche, The Chinese University of Hong Kong [Hong Kong], CHU Bordeaux [Bordeaux], University of Malaya [Kuala Lumpur, Malaisie], Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), and CCSD, Accord Elsevier
Subjects: Liver Cirrhosis, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Overweight, Gastroenterology, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Non-alcoholic Fatty Liver Disease, Internal medicine, Nonalcoholic fatty liver disease, medicine, Humans, Obesity, 2. Zero hunger, Hepatology, Receiver operating characteristic, business.industry, nutritional and metabolic diseases, medicine.disease, digestive system diseases, Advanced fibrosis, 3. Good health, [SDV] Life Sciences [q-bio], Normal body mass index, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, medicine.symptom, business, Body mass index
Abstract: International audience; Because only a minority of patients with nonalcoholic fatty liver disease (NAFLD) have advanced fibrosis and would eventually develop liver-related complications, current guidelines recommend initial assessment with noninvasive tests of fibrosis.1-3 Most previous studies focused on overweight and obese patients. Despite a strong association between obesity and NAFLD, 3%-30% of people with relatively normal body mass index (BMI) may still have NAFLD.4,5 Hence, this study aims to evaluate the performance of the common noninvasive tests in non-obese (BMI
Published: 2019

31. A novel spleen-dedicated stiffness measurement by FibroScan® improves the screening of high-risk oesophageal varices

Author: Federico Ravaioli, M. Rosselli, Giuseppe Mazzella, Mirella Fraquelli, Antonio Colecchia, Corina Rusu, Nathalie Ganne-Carrié, Giovanni Marasco, Paul Calès, Davide Festi, Horia Stefanescu, Victor de Ledinghen, Pietro Andreone, Stefanescu H., Marasco G., Cales P., Fraquelli M., Rosselli M., Ganne-Carrie N., de Ledinghen V., Ravaioli F., Colecchia A., Rusu C., Andreone P., Mazzella G., Festi D., Regional Institute of Gastroenterology and Hepatology [Cluj-Napoca], Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), II Gastroenterology Unit, Department of Medicine, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Physiopathologie du cancer du foie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, and Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO)
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Baveno VI criteria, liver stiffness measurement, portal hypertension, spleen stiffness measurement, Chronic liver disease, Esophageal and Gastric Varices, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Liver stiffness, Predictive Value of Tests, Internal medicine, medicine, Humans, Prospective Studies, ComputingMilieux_MISCELLANEOUS, Aged, Hepatology, medicine.diagnostic_test, business.industry, Platelet Count, Liver Diseases, Reproducibility of Results, Middle Aged, medicine.disease, 3. Good health, Endoscopy, Logistic Models, 030220 oncology & carcinogenesis, Multivariate Analysis, Portal hypertension, Elasticity Imaging Techniques, 030211 gastroenterology & hepatology, Female, business, Varices, Spleen
Abstract: Background & Aims Several non-invasive tests (NITs) have been developed to diagnose oesophageal varices (EV), including the recent Baveno VI criteria to rule out high-risk varices (HRV). Spleen stiffness measurement (SSM) with the standard FibroScan (R) (SSM@50Hz) has been evaluated. However, the EV grading could be underestimated because of a ceiling threshold (75 kPa) of the SSM@50Hz. The aims were to evaluate SSM by a novel spleen-dedicated FibroScan (R) (SSM@100Hz) for EV diagnosis compared with SSM@50Hz, other validated NITs and Baveno VI criteria. Methods This prospective multicentre study consecutively enrolled patients with chronic liver disease; blood data, endoscopy, liver stiffness measurement (LSM), SSM@50Hz and SSM@100Hz were collected. Results Two hundred and sixty patients met inclusion criteria. SSM@100Hz success rate was significantly higher than that of SSM@50Hz (92.5% vs 76.0%, P < .001). SSM@100Hz accuracy for the presence of EV (AUC = 0.728) and HRV (AUC = 0.756) was higher than in other NITs. SSM@100Hz AUC for large EV (0.782) was higher than SSM@50Hz (0.720, P = .027). AUC for HRV with SSM@100Hz (0.780) was higher than with LSM (0.615, P < .001). The spared endoscopy rate of Baveno VI criteria (8.1%) was significantly increased by the combination to SSM@50Hz (26.5%) or SSM@100Hz (38.9%, P < .001 vs others). The missed HRV rate was, respectively, 0% and 4.7% for combinations. Conclusions SSM@100Hz is a new performant non-invasive marker for EV and HRV providing a higher accuracy than SSM@50Hz and other NITs. The combination of Baveno VI criteria and SSM@100Hz significantly increased the spared endoscopy rate compared to Baveno VI criteria alone or combined with SSM@50Hz. Clinical trial number: NCT02180113.
Published: 2019

32. Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment a prospective cohort study

Author: Albert Tran, Victor de Ledinghen, Armand Abergel, Céline Dorival, Olivier Chazouillères, Louis d’Alteroche, Isabelle Rosa, Didier Samuel, Moana Gelu-Simeon, Laurent Alric, Vincent Leroy, Jérôme Gournay, François Habersetzer, Dominique Guyader, Stanislas Pol, Véronique Loustaud-Ratti, Ghassan Riachi, Jean-Pierre Bronowicki, Hélène Fontaine, Anne Minello, Christophe Hézode, Philippe Mathurin, Claire Geist, Nathalie Ganne, Mélanie Simony, Dominique Thabut, François Raffi, Xavier Causse, Patrick Marcellin, Sophie Metivier, Paul Calès, Isabelle Portal, Marc Bourlière, Dominique Larrey, Fabien Zoulim, Fabrice Carrat, Alpha Diallo, Georges Haour, Tarik Asselah, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), ANRS France Recherche Nord & sud Sida-hiv hépatites, Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-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), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre 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 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), 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 [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire de Nice (CHU Nice), Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, 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), 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), Sorbonne Université (SU), Physiopathologie des Maladies Inflammatoires de l'Intestin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Rouen, Normandie Université (NU), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Image Science for Interventional Techniques (ISIT), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Centre National de la Recherche Scientifique (CNRS), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), 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), Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional d'Orléans (CHRO), Service d'Hépato-gastro-entérologie [CHR Metz-Thionville], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Equipe EPICAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Intercommunal de Créteil (CHIC), Institut de recherche en santé, environnement et travail (Irset), 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 ), Aix Marseille Université (AMU), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], 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), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), 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), CHU Toulouse [Toulouse], 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], CCSD, Accord Elsevier, 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), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Cirrhosis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Liver transplantation, Antiviral Agents, Gastroenterology, 03 medical and health sciences, Liver disease, Viewpoint, 0302 clinical medicine, Internal medicine, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Aged, Proportional Hazards Models, business.industry, Incidence, Liver Neoplasms, Hazard ratio, General Medicine, Hepatitis C, Hepatitis C, Chronic, Middle Aged, Hepatology, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Hepatocellular carcinoma, Female, France, business
Abstract: Although direct-acting antivirals have been used extensively to treat patients with chronic hepatitis C virus (HCV) infection, their clinical effectiveness has not been well reported. We compared the incidence of death, hepatocellular carcinoma, and decompensated cirrhosis between patients treated with direct-acting antivirals and those untreated, in the French ANRS CO22 Hepather cohort.We did a prospective study in adult patients with chronic HCV infection enrolled from 32 expert hepatology centres in France. We excluded patients with chronic hepatitis B, those with a history of decompensated cirrhosis, hepatocellular carcinoma, or liver transplantation, and patients who were treated with interferon-ribavirin with or without first-generation protease inhibitors. Co-primary study outcomes were incidence of all-cause mortality, hepatocellular carcinoma, and decompensated cirrhosis. The association between direct-acting antivirals and these outcomes was quantified using time-dependent Cox proportional hazards models. This study is registered with ClinicalTrials.gov, number NCT01953458.Between Aug 6, 2012, and Dec 31, 2015, 10 166 patients were eligible for the study. 9895 (97%) patients had available follow-up information and were included in analyses. Median follow-up was 33·4 months (IQR 24·0-40·7). Treatment with direct-acting antivirals was initiated during follow-up in 7344 patients, and 2551 patients remained untreated at the final follow-up visit. During follow-up, 218 patients died (129 treated, 89 untreated), 258 reported hepatocellular carcinoma (187 treated, 71 untreated), and 106 had decompensated cirrhosis (74 treated, 32 untreated). Exposure to direct-acting antivirals was associated with increased risk for hepatocellular carcinoma (unadjusted hazard ratio [HR] 2·77, 95% CI 2·07-3·71) and decompensated cirrhosis (3·83, 2·29-6·42). After adjustment for variables (age, sex, body-mass index, geographical origin, infection route, fibrosis score, HCV treatment-naive, HCV genotype, alcohol consumption, diabetes, arterial hypertension, biological variables, and model for end-stage liver disease score in patients with cirrhosis), exposure to direct-acting antivirals was associated with a decrease in all-cause mortality (adjusted HR 0·48, 95% CI 0·33-0·70) and hepatocellular carcinoma (0·66, 0·46-0·93), and was not associated with decompensated cirrhosis (1·14, 0·57-2·27).Treatment with direct-acting antivirals is associated with reduced risk for mortality and hepatocellular carcinoma and should be considered in all patients with chronic HCV infection.INSERM-ANRS (France Recherche NordSud Sida-HIV Hépatites), ANR (Agence Nationale de la Recherche), DGS (Direction Générale de la Santé), MSD, Janssen, Gilead, AbbVie, Bristol-Myers Squibb, and Roche.
Published: 2019

33. Impact of Obesity and Alanine Aminotransferase Levels on the Diagnostic Accuracy for Advanced Liver Fibrosis of Noninvasive Tools in Patients with Nonalcoholic Fatty Liver Disease

Author: Anna Ludovica Fracanzani, Grace Lai-Hung Wong, Anthony W.H. Chan, Rosa Lombardi, Salvatore Guastella, Julien Vergniol, Victor de Ledinghen, Calogero Cammà, Henry Lik-Yuen Chan, Vincent Wai-Sun Wong, Jean Baptiste Hiriart, Brigitte Le-Bail, Aurora Giannetti, Antonio Craxì, Salvatore Petta, Elisabetta Bugianesi, Wassil Merrouche, Petta S., Wai-Sun Wong V., Bugianesi E., Fracanzani A.L., Camma C., Hiriart J.-B., Lai-Hung Wong G., Vergniol J., Wing-Hung Chan A., Giannetti A., Merrouche W., Lik-Yuen Chan H., Le-Bail B., Lombardi R., Guastella S., Craxi A., and De Ledinghen V.
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Biopsy, Severity of Illness Index, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Predictive Value of Tests, Fibrosis, Internal medicine, Severity of illness, Nonalcoholic fatty liver disease, medicine, Humans, Aspartate Aminotransferases, Obesity, NASH, FIBROSIS, Hepatology, medicine.diagnostic_test, business.industry, Fatty liver, Alanine Transaminase, Middle Aged, medicine.disease, Liver, ROC Curve, 030220 oncology & carcinogenesis, Predictive value of tests, Elasticity Imaging Techniques, Female, 030211 gastroenterology & hepatology, Steatosis, Hepatic fibrosis, business, Biomarkers
Abstract: Some evidence suggests an interference of obesity and alanine aminotransferase (ALT) levels on the diagnostic accuracy for advanced fibrosis of noninvasive tools such as liver stiffness measurement (LSM) by FibroScan, Fibrosis-4 (FIB-4), and nonalcoholic fatty liver disease fibrosis score (NFS). We assessed whether the diagnostic accuracy of LSM, Fibrosis-4 (FIB-4), and NFS and strategies based on the combination of these tools is affected by obesity and/or ALT levels.METHODS:We analyzed data from 968 patients with a histological diagnosis of nonalcoholic fatty liver disease. FIB-4, NFS, and LSM by FibroScan were measured.RESULTS:LSM was better than both FIB-4 and NFS for staging F3-F4 fibrosis area under the receiver operating characteristic curve test (AUC) 0.863, 0.777, and 0.765, respectively; P < 0.001 for both), showing higher accuracy and higher negative predictive value (NPV), but lower positive predictive value (PPV). LSM worked less well in high ALT (>100 IU) (AUC 0.811 vs 0.877, P = 0.04; PPV 57.5% vs 62.4%; NPV 90.7% vs 94%) or obese patients (AUC 0.786 vs 0.902, P < 0.001; PPV 58.7% vs 64.8%; NPV 88.3% vs 95.2%), the latter not being affected by the M or XL probe. Consistently, LSM worked better in terms of AUC and accuracy compared with both FIB-4 and NFS only in nonobese or high ALT patients, even with always keeping a slightly lower PPV. A serial combination of FIB-4 or NFS with LSM as the second test in patients in the gray area of the first test retained - in most scenarios - similar PPV and NPV compared with LSM alone. These strategies also increased the diagnostic accuracy of about 20% in all groups of patients, even if with a lower overall accuracy in obese patients (71.3% and 67.1% for FIB-4 and NFS as the first test, respectively) compared to nonobese patients (81.9% and 82.4% for FIB-4 and NFS as the first test, respectively).CONCLUSIONS:All tested noninvasive tools have overall better NPV than PPV. LSM has a better diagnostic accuracy for advanced fibrosis than both FIB-4 and NFS only in nonobese and/or low ALT patients. Serial combination strategies are better than a single tool strategy, regardless of obesity and ALT levels, although the accuracy is lower in obese patients.
Published: 2019

34. SAT-490-No Impact of Direct-Acting Antivirals on Recurrent Hepatocellular Carcinoma Tumour Growth in the ANRS CO22 Hepather Cohort

Author: Tarik Asselah, Pol Stanislas, Fabien Zoulim, Isabelle Rosa, A.V. Pichard, Hélène Fontaine, Olivier Chazouillères, Correas Jean Michel, Dominique Larrey, Marc Bourlière, Nathalie Ganne, Véronique Loustaud-Ratti, Jérôme Gournay, Philippe Mathurin, Vincent Leroy, Albert Tran, Jean-Pierre Bronowicki, Didier Samuel, Dorival Celine, Dominique Guyader, Paul Calès, Christophe Hézode, Metivier Sophie, Victor de Ledinghen, Fabrice Carrat, Département d'hépatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hospices Civils de Lyon, Departement de Neurologie (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 Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Lille, Épidémiologie clinique des maladies virales chroniques [iPLesp] (CLEPIVIR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Physiopathologie du système immunitaire (Inserm U1223), and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: Oncology, medicine.medical_specialty, Hepatology, business.industry, Internal medicine, [SDV]Life Sciences [q-bio], Cohort, Medicine, business, DIRECT ACTING ANTIVIRALS, Recurrent Hepatocellular Carcinoma
Abstract: International audience
Published: 2019

35. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Author: Zobair M Younossi, Vlad Ratziu, Rohit Loomba, Mary Rinella, Quentin M Anstee, Zachary Goodman, Pierre Bedossa, Andreas Geier, Susanne Beckebaum, Philip N Newsome, David Sheridan, Muhammad Y Sheikh, James Trotter, Whitfield Knapple, Eric Lawitz, Manal F Abdelmalek, Kris V Kowdley, Aldo J Montano-Loza, Jerome Boursier, Philippe Mathurin, Elisabetta Bugianesi, Giuseppe Mazzella, Antonio Olveira, Helena Cortez-Pinto, Isabel Graupera, David Orr, Lise Lotte Gluud, Jean-Francois Dufour, David Shapiro, Jason Campagna, Luna Zaru, Leigh MacConell, Reshma Shringarpure, Stephen Harrison, Arun J Sanyal, Manal Abdelmalek, Gary Abrams, Humberto Aguilar, Aijaz Ahmed, Elmar Aigner, Guruprasad Aithal, Aftab Ala, William Alazawi, Agustin Albillos, Michael Allison, Sfa Al-Shamma, Raul Andrade, Pietro Andreone, Mario Angelico, Victor Ankoma-Sey, Quentin Anstee, Rodolphe Anty, Victor Araya, Juan Ignacio Arenas Ruiz, Perttu Arkkila, Marty Arora, Tarik Asselah, Jennifer Au, Oyekoya Ayonrinde, Robert James Bailey, Maya Balakrishnan, Kiran Bambha, Meena Bansal, Sidney Barritt, John Bate, Jorge Beato, Jaideep Behari, Pablo Bellot, Ziv Ben Ari, Michael Bennett, Marina Berenguer, Benedetta Terziroli Beretta-Piccoli, Thomas Berg, Maurizio Bonacini, Lucia Bonet, Brian Borg, Marc Bourliere, William Bowman, David Bradley, Marija Brankovic, Marius Braun, Jean-Pierre Bronowicki, Savino Bruno, Cindy Cai, Amy Calderon, José Luis Calleja Panero, Elizabeth Carey, Michal Carmiel, Jose Antonio Carrión, Matthew Cave, Cristina Chagas, Tawfik Chami, Alan Chang, Allan Coates, Jeremy Cobbold, Charlote Costentin, Kathleen Corey, Lynsey Corless, Javier Crespo, Oscar Cruz Pereira, Victor de Ledinghen, Andrew deLemos, Moises Diago, Mamie Dong, Jean-François Dufour, Predrag Dugalic, Winston Dunn, Magby Elkhashab, Michael Epstein, Maria Desamparados Escudero-Garcia, Ohad Etzion, Larry Evans, Robert Falcone, Conrado Fernandez, Jose Ferreira, Scott Fink, Kevin Finnegan, Roberto Firpi-Morell, Annarosa Floreani, Thierry Fontanges, Ryan Ford, Ewan Forrest, Andrew Fowell, Anna Ludovica Fracanzani, Sven Francque, Bradley Freilich, Juan Frias, Michael Fuchs, Javier Fuentes, Michael Galambos, Juan Gallegos, Anja Geerts, Jacob George, Maged Ghali, Reem Ghalib, Pierre Gholam, Pere Gines, Norman Gitlin, Tobias Goeser, John Goff, Stuart Gordon, Frederic Gordon, Odile Goria, Shaun Greer, Alla Grigorian, Henning Gronbaek, Maeva Guillaume, Naresh Gunaratnam, Dina Halegoua-De Marzio, Bilal Hameed, Stephanie Hametner, James Hamilton, Marek Hartleb, Tarek Hassanein, Dieter Häussinger, Paul Hellstern, Robert Herring, Eva Heurich, Christophe Hezode, Holger Hinrichsen, Peter Holland Fischer, Yves Horsmans, Jonathan Huang, Hyder Hussaini, Antoine Jakiche, Lennox Jeffers, Blake Jones, Rosa Jorge, Francisco Jorquera, Shoba Joshi, Alisan Kahraman, Kelly Kaita, Nicholas Karyotakis, Zeid Kayali, Stergios Kechagias, Thomas Kepczyk, Mandana Khalili, Hicham Khallafi, Johannes Kluwe, Anita Kohli, Kevin Korenblat, Kris Kowdley, Aleksander Krag, Richard Krause, Andreas Kremer, Karen Krok, Miodrag Krstic, Marcelo Kugelmas, Sonal Kumar, Scott Kuwada, Damien Labarriere, Michelle Lai, Wim Laleman, Pietro Lampertico, Alice Lee, Vincent Leroy, Steven Lidofsky, Tina Huey Lim, Joseph Lim, Donald Lipkis, Ester Little, Amadeo Lonardo, Michelle Long, Velimir Anthony Christopher Luketic, Yoav Lurie, Guilherme Macedo, Joana Magalhaes, Mihály Makara, Benedict Maliakkal, Michael Manns, Pinelopi Manousou, Parvez Mantry, Giulio Marchesini, Carla Marinho, Paul Marotta, Hanns-Ulrich Marschall, Linda Martinez, Marlyn Mayo, Mark McCullen, William McLaughlin, Uta Merle, Raphael Merriman, Apurva Modi, Esther Molina, Aldo Montano-Loza, Carlos Monteverde, Amilcar Morales Cardona, Sulleman Moreea, Christophe Moreno, Filomena Morisco, Abdullah Mubarak, Beat Muellhaupt, Sandeep Mukherjee, Tobias Müller, Aleksandar Nagorni, Jahnavi Naik, Guy Neff, Moises Nevah, Philip Newsome, Eric Nguyen-Khac, Mazen Noureddin, Jude Oben, Hans Orlent, James Orr, Grisell Ortiz-Lasanta, Violaine Ozenne, Prashant Pandya, Angelo Paredes, James Park, Joykumar Patel, Keyur Patel, Sonali Paul, Heather Patton, Markus Peck-Radosavljevic, Salvatore Petta, Stephen Pianko, Anna Piekarska, Neville Pimstone, Joseph Pisegna, Paul Pockros, Stanislas Pol, Michael Porayko, John Poulos, David Pound, Joe Pouzar, Jose Presa Ramos, Nikolaos Pyrsopoulos, Nila Rafiq, Kate Muller, Alnoor Ramji, Ravi Ravinuthala, Chakradhar Reddy, Gautham Reddy K G, K. Rajender Reddy K R, Frederic Regenstein, Robert Reindollar, Justin Reynolds, Andres Riera, Jose Rivera Acosta, Geert Robaeys, Stuart Roberts, Federico Rodriguez-Perez, Sandor Romero, Manuel Romero-Gomez, Raymond Rubin, Mariagrazia Rumi, Simon Rushbrook, Christian Rust, Michael Ryan, Rifaat Safadi, Adnan Said, Kimmo Salminen, Didier Samuel, John Santoro, Arun Sanyal, Souvik Sarkar, Cynthia Schaeffer, Jörn Schattenberg, Ingolf Schiefke, Eugene Schiff, Wolfgang Schmidt, Jeffrey Schneider, Jeoffrey Schouten, Michael Schultz, Giada Sebastiani, David Semela, Thomas Sepe, Aasim Sheikh, Muhammad Sheikh, Kenneth Sherman, Oren Shibolet, Mitchell Shiffman, Asma Siddique, Cyril Sieberhagen, Samuel Sigal, Katarzyna Sikorska, Krzysztof Simon, Marie Sinclair, Richard Skoien, Joel Solis, Siddharth Sood, Bob Souder, James Spivey, Per Stal, Laura Stinton, Simone Strasser, Petar Svorcan, Gyongzi Szabo, Andrew Talal, Edward Tam, Brent Tetri, Paul Thuluvath, Hillel Tobias, Krzysztof Tomasiewicz, Dawn Torres, Albert Tran, Michael Trauner, Christian Trautwein, Emanuel Tsochatzis, Esther Unitt, Victor Vargas, Istvan Varkonyi, Ella Veitsman, Umberto Vespasiani Gentilucci, David Victor, John Vierling, Catherine Vincent, Aron Vincze, Manfred von der Ohe, Natasha Von Roenn, Raj Vuppalanchi, Michael Waters, Kymberly Watt, Julia Wattacheril, Martin Weltman, Amanda Wieland, Gregory Wiener, Alonzo Williams A, Jeffrey Williams J, Jason Wilson, Maria Yataco, Eric Yoshida, Ziad Younes, Liyun Yuan, Adam Zivony, Donald Zogg, Heinz Zoller, Fabien Zoulim, Eli Zuckerman, Massimo Zuin, Younossi Z.M., Ratziu V., Loomba R., Rinella M., Anstee Q.M., Goodman Z., Bedossa P., Geier A., Beckebaum S., Newsome P.N., Sheridan D., Sheikh M.Y., Trotter J., Knapple W., Lawitz E., Abdelmalek M.F., Kowdley K.V., Montano-Loza A.J., Boursier J., Mathurin P., Bugianesi E., Mazzella G., Olveira A., Cortez-Pinto H., Graupera I., Orr D., Gluud L.L., Dufour J.-F., Shapiro D., Campagna J., Zaru L., MacConell L., Shringarpure R., Harrison S., Sanyal A.J., Abdelmalek M., Abrams G., Aguilar H., Ahmed A., Aigner E., Aithal G., Ala A., Alazawi W., Albillos A., Allison M., Al-Shamma S., Andrade R., Andreone P., Angelico M., Ankoma-Sey V., Anstee Q., Anty R., Araya V., Arenas Ruiz J.I., Arkkila P., Arora M., Asselah T., Au J., Ayonrinde O., Bailey R.J., Balakrishnan M., Bambha K., Bansal M., Barritt S., Bate J., Beato J., Behari J., Bellot P., Ben Ari Z., Bennett M., Berenguer M., Beretta-Piccoli B.T., Berg T., Bonacini M., Bonet L., Borg B., Bourliere M., Bowman W., Bradley D., Brankovic M., Braun M., Bronowicki J.-P., Bruno S., Cai C., Calleja Panero J.L., Carey E., Carmiel M., Carrion J.A., Cave M., Chagas C., Chami T., Chang A., Coates A., Cobbold J., Corey K., Corless L., Crespo J., Cruz Pereira O., de Ledinghen V., deLemos A., Diago M., Dugalic P., Dunn W., Elkhashab M., Epstein M., Escudero-Garcia M.D., Etzion O., Evans L., Falcone R., Fernandez C., Ferreira J., Fink S., Finnegan K., Firpi-Morell R., Floreani A., Fontanges T., Ford R., Forrest E., Fowell A., Fracanzani A.L., Francque S., Freilich B., Frias J., Fuchs M., Fuentes J., Galambos M., Gallegos J., Geerts A., George J., Ghali M., Ghalib R., Gholam P., Gines P., Gitlin N., Goeser T., Goff J., Gordon S., Gordon F., Goria O., Greer S., Grigorian A., Gronbaek H., Guillaume M., Gunaratnam N., Halegoua-De Marzio D., Hameed B., Hametner S., Hamilton J., Hartleb M., Hassanein T., Haussinger D., Hellstern P., Herring R., Heurich E., Hezode C., Hinrichsen H., Holland Fischer P., Horsmans Y., Huang J., Jakiche A., Jeffers L., Jones B., Jorge R., Jorquera F., Kahraman A., Kaita K., Karyotakis N., Kayali Z., Kechagias S., Kepczyk T., Khalili M., Khallafi H., Kluwe J., Kohli A., Korenblat K., Kowdley K., Krag A., Krause R., Kremer A., Krok K., Krstic M., Kugelmas M., Kumar S., Labarriere D., Lai M., Lampertico P., Lee A., Leroy V., Lidofsky S., Lim T.H., Lim J., Lipkis D., Little E., Lonardo A., Long M., Lurie Y., Macedo G., Makara M., Maliakkal B., Manns M., Manousou P., Mantry P., Marchesini G., Marinho C., Marotta P., Marschall H.-U., Mayo M., McCullen M., McLaughlin W., Merriman R., Modi A., Molina E., Montano-Loza A., Monteverde C., Moreea S., Moreno C., Morisco F., Mubarak A., Muellhaupt B., Mukherjee S., Muller T., Nagorni A., Naik J., Neff G., Nevah M., Newsome P., Nguyen-Khac E., Noureddin M., Oben J., Orlent H., Orr J., Ortiz-Lasanta G., Ozenne V., Pandya P., Paredes A., Park J., Patel J., Patel K., Uta M., Patton H., Peck-Radosavljevic M., Petta S., Pianko S., Piekarska A., Pimstone N., Pockros P., Pol S., Porayko M., Poulos J., Pound D., Pouzar J., Presa Ramos J., Pyrsopoulos N., Rafiq N., Muller K., Ramji A., Ravinuthala R., Reddy C., Reddy K G G., Reddy K R K.R., Regenstein F., Reindollar R., Riera A., Rivera Acosta J., Robaeys G., Roberts S., Rodriguez-Perez F., Romero-Gomez M., Rubin R., Rumi M., Rushbrook S., Rust C., Ryan M., Safadi R., Said A., Salminen K., Samuel D., Santoro 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M., Ratziu, V., Loomba, R., Rinella, M., Anstee, Q. M., Goodman, Z., Bedossa, P., Geier, A., Beckebaum, S., Newsome, P. N., Sheridan, D., Sheikh, M. Y., Trotter, J., Knapple, W., Lawitz, E., Abdelmalek, M. F., Kowdley, K. V., Montano-Loza, A. J., Boursier, J., Mathurin, P., Bugianesi, E., Mazzella, G., Olveira, A., Cortez-Pinto, H., Graupera, I., Orr, D., Gluud, L. L., Dufour, J. -F., Shapiro, D., Campagna, J., Zaru, L., Macconell, L., Shringarpure, R., Harrison, S., Sanyal, A. J., Abdelmalek, M., Abrams, G., Aguilar, H., Ahmed, A., Aigner, E., Aithal, G., Ala, A., Alazawi, W., Albillos, A., Allison, M., Al-Shamma, S., Andrade, R., Andreone, P., Angelico, M., Ankoma-Sey, V., Anstee, Q., Anty, R., Araya, V., Arenas Ruiz, J. I., Arkkila, P., Arora, M., Asselah, T., Au, J., Ayonrinde, O., Bailey, R. J., Balakrishnan, M., Bambha, K., Bansal, M., Barritt, S., Bate, J., Beato, J., Behari, J., Bellot, P., Ben Ari, Z., Bennett, M., Berenguer, M., Beretta-Piccoli, B. 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L., Francque, S., Freilich, B., Frias, J., Fuchs, M., Fuentes, J., Galambos, M., Gallegos, J., Geerts, A., George, J., Ghali, M., Ghalib, R., Gholam, P., Gines, P., Gitlin, N., Goeser, T., Goff, J., Gordon, S., Gordon, F., Goria, O., Greer, S., Grigorian, A., Gronbaek, H., Guillaume, M., Gunaratnam, N., Halegoua-De Marzio, D., Hameed, B., Hametner, S., Hamilton, J., Hartleb, M., Hassanein, T., Haussinger, D., Hellstern, P., Herring, R., Heurich, E., Hezode, C., Hinrichsen, H., Holland Fischer, P., Horsmans, Y., Huang, J., Jakiche, A., Jeffers, L., Jones, B., Jorge, R., Jorquera, F., Kahraman, A., Kaita, K., Karyotakis, N., Kayali, Z., Kechagias, S., Kepczyk, T., Khalili, M., Khallafi, H., Kluwe, J., Kohli, A., Korenblat, K., Kowdley, K., Krag, A., Krause, R., Kremer, A., Krok, K., Krstic, M., Kugelmas, M., Kumar, S., Labarriere, D., Lai, M., Lampertico, P., Lee, A., Leroy, V., Lidofsky, S., Lim, T. H., Lim, J., Lipkis, D., Little, E., Lonardo, A., Long, M., Lurie, Y., Macedo, G., Makara, M., Maliakkal, B., Manns, M., Manousou, P., Mantry, P., Marchesini, G., Marinho, C., Marotta, P., Marschall, H. -U., Mayo, M., Mccullen, M., Mclaughlin, W., Merriman, R., Modi, A., Molina, E., Montano-Loza, A., Monteverde, C., Moreea, S., Moreno, C., Morisco, F., Mubarak, A., Muellhaupt, B., Mukherjee, S., Muller, T., Nagorni, A., Naik, J., Neff, G., Nevah, M., Newsome, P., Nguyen-Khac, E., Noureddin, M., Oben, J., Orlent, H., Orr, J., Ortiz-Lasanta, G., Ozenne, V., Pandya, P., Paredes, A., Park, J., Patel, J., Patel, K., Uta, M., Patton, H., Peck-Radosavljevic, M., Petta, S., Pianko, S., Piekarska, A., Pimstone, N., Pockros, P., Pol, S., Porayko, M., Poulos, J., Pound, D., Pouzar, J., Presa Ramos, J., Pyrsopoulos, N., Rafiq, N., Muller, K., Ramji, A., Ravinuthala, R., Reddy, C., Reddy K G, G., Reddy K R, K. R., Regenstein, F., Reindollar, R., Riera, A., Rivera Acosta, J., Robaeys, G., Roberts, S., Rodriguez-Perez, F., Romero-Gomez, M., Rubin, R., Rumi, M., Rushbrook, S., Rust, C., Ryan, M., Safadi, R., Said, A., Salminen, K., Samuel, D., Santoro, J., Sanyal, A., Sarkar, S., Schaeffer, C., Schattenberg, J., Schiefke, I., Schiff, E., Schmidt, W., Schneider, J., Schouten, J., Schultz, M., Sebastiani, G., Semela, D., Sepe, T., Sheikh, A., Sheikh, M., Sherman, K., Shibolet, O., Shiffman, M., Siddique, A., Sieberhagen, C., Sigal, S., Sikorska, K., Simon, K., Sinclair, M., Skoien, R., Solis, J., Sood, S., Souder, B., Spivey, J., Stal, P., Stinton, L., Strasser, S., Svorcan, P., Szabo, G., Talal, A., Tam, E., Tetri, B., Thuluvath, P., Tobias, H., Tomasiewicz, K., Torres, D., Trauner, M., Trautwein, C., Tsochatzis, E., Unitt, E., Vargas, V., Varkonyi, I., Veitsman, E., Vespasiani Gentilucci, U., Victor, D., Vierling, J., Vincent, C., Vincze, A., von der Ohe, M., Von Roenn, N., Vuppalanchi, R., Waters, M., Watt, K., Weltman, M., Wieland, A., Wiener, G., Williams A, A., Williams J, J., Wilson, J., Yataco, M., Yoshida, E., Younes, Z., Yuan, L., Zivony, A., Zogg, D., Zoller, H., Zoulim, F., Zuckerman, E., Zuin, M., Younossi, Zobair M, Ratziu, Vlad, Loomba, Rohit, Rinella, Mary, Anstee, Quentin M, Goodman, Zachary, Bedossa, Pierre, Geier, Andrea, Beckebaum, Susanne, Newsome, Philip N, Sheridan, David, Sheikh, Muhammad Y, Trotter, Jame, Knapple, Whitfield, Lawitz, Eric, Abdelmalek, Manal F, Kowdley, Kris V, Montano-Loza, Aldo J, Boursier, Jerome, Mathurin, Philippe, Bugianesi, Elisabetta, Mazzella, Giuseppe, Olveira, Antonio, Cortez-Pinto, Helena, Graupera, Isabel, Orr, David, Gluud, Lise Lotte, Dufour, Jean-Francoi, Shapiro, David, Campagna, Jason, Zaru, Luna, MacConell, Leigh, Shringarpure, Reshma, Harrison, Stephen, Sanyal, Arun J, Abdelmalek, Manal, Abrams, Gary, Aguilar, Humberto, Ahmed, Aijaz, Aigner, Elmar, Aithal, Guruprasad, Ala, Aftab, Alazawi, William, Albillos, Agustin, Allison, Michael, Al-Shamma, Sfa, Andrade, Raul, Andreone, Pietro, Angelico, Mario, Ankoma-Sey, Victor, Anstee, Quentin, Anty, Rodolphe, Araya, Victor, Arenas Ruiz, Juan Ignacio, Arkkila, Perttu, Arora, Marty, Asselah, Tarik, Au, Jennifer, Ayonrinde, Oyekoya, Bailey, Robert Jame, Balakrishnan, Maya, Bambha, Kiran, Bansal, Meena, Barritt, Sidney, Bate, John, Beato, Jorge, Behari, Jaideep, Bellot, Pablo, Ben Ari, Ziv, Bennett, Michael, Berenguer, Marina, Beretta-Piccoli, Benedetta Terziroli, Berg, Thoma, Bonacini, Maurizio, Bonet, Lucia, Borg, Brian, Bourliere, Marc, Bowman, William, Bradley, David, Brankovic, Marija, Braun, Mariu, Bronowicki, Jean-Pierre, Bruno, Savino, Cai, Cindy, Calleja Panero, José Lui, Carey, Elizabeth, Carmiel, Michal, Carrión, Jose Antonio, Cave, Matthew, Chagas, Cristina, Chami, Tawfik, Chang, Alan, Coates, Allan, Cobbold, Jeremy, Corey, Kathleen, Corless, Lynsey, Crespo, Javier, Cruz Pereira, Oscar, de Ledinghen, Victor, deLemos, Andrew, Diago, Moise, Dufour, Jean-Françoi, Dugalic, Predrag, Dunn, Winston, Elkhashab, Magby, Epstein, Michael, Escudero-Garcia, Maria Desamparado, Etzion, Ohad, Evans, Larry, Falcone, Robert, Fernandez, Conrado, Ferreira, Jose, Fink, Scott, Finnegan, Kevin, Firpi-Morell, Roberto, Floreani, Annarosa, Fontanges, Thierry, Ford, Ryan, Forrest, Ewan, Fowell, Andrew, Fracanzani, Anna Ludovica, Francque, Sven, Freilich, Bradley, Frias, Juan, Fuchs, Michael, Fuentes, Javier, Galambos, Michael, Gallegos, Juan, Geerts, Anja, George, Jacob, Ghali, Maged, Ghalib, Reem, Gholam, Pierre, Gines, Pere, Gitlin, Norman, Goeser, Tobia, Goff, John, Gordon, Stuart, Gordon, Frederic, Goria, Odile, Greer, Shaun, Grigorian, Alla, Gronbaek, Henning, Guillaume, Maeva, Gunaratnam, Naresh, Halegoua-De Marzio, Dina, Hameed, Bilal, Hametner, Stephanie, Hamilton, Jame, Hartleb, Marek, Hassanein, Tarek, Häussinger, Dieter, Hellstern, Paul, Herring, Robert, Heurich, Eva, Hezode, Christophe, Hinrichsen, Holger, Holland Fischer, Peter, Horsmans, Yve, Huang, Jonathan, Jakiche, Antoine, Jeffers, Lennox, Jones, Blake, Jorge, Rosa, Jorquera, Francisco, Kahraman, Alisan, Kaita, Kelly, Karyotakis, Nichola, Kayali, Zeid, Kechagias, Stergio, Kepczyk, Thoma, Khalili, Mandana, Khallafi, Hicham, Kluwe, Johanne, Kohli, Anita, Korenblat, Kevin, Kowdley, Kri, Krag, Aleksander, Krause, Richard, Kremer, Andrea, Krok, Karen, Krstic, Miodrag, Kugelmas, Marcelo, Kumar, Sonal, Labarriere, Damien, Lai, Michelle, Lampertico, Pietro, Lee, Alice, Leroy, Vincent, Lidofsky, Steven, Lim, Tina Huey, Lim, Joseph, Lipkis, Donald, Little, Ester, Lonardo, Amadeo, Long, Michelle, Lurie, Yoav, Macedo, Guilherme, Makara, Mihály, Maliakkal, Benedict, Manns, Michael, Manousou, Pinelopi, Mantry, Parvez, Marchesini, Giulio, Marinho, Carla, Marotta, Paul, Marschall, Hanns-Ulrich, Mayo, Marlyn, McCullen, Mark, McLaughlin, William, Merriman, Raphael, Modi, Apurva, Molina, Esther, Montano-Loza, Aldo, Monteverde, Carlo, Moreea, Sulleman, Moreno, Christophe, Morisco, Filomena, Mubarak, Abdullah, Muellhaupt, Beat, Mukherjee, Sandeep, Müller, Tobia, Nagorni, Aleksandar, Naik, Jahnavi, Neff, Guy, Nevah, Moise, Newsome, Philip, Nguyen-Khac, Eric, Noureddin, Mazen, Oben, Jude, Orlent, Han, Orr, Jame, Ortiz-Lasanta, Grisell, Ozenne, Violaine, Pandya, Prashant, Paredes, Angelo, Park, Jame, Patel, Joykumar, Patel, Keyur, Uta, Merle, Patton, Heather, Peck-Radosavljevic, Marku, Petta, Salvatore, Pianko, Stephen, Piekarska, Anna, Pimstone, Neville, Pockros, Paul, Pol, Stanisla, Porayko, Michael, Poulos, John, Pound, David, Pouzar, Joe, Presa Ramos, Jose, Pyrsopoulos, Nikolao, Rafiq, Nila, Muller, Kate, Ramji, Alnoor, Ravinuthala, Ravi, Reddy, Chakradhar, Reddy K G, Gautham, Reddy K R, K. Rajender, Regenstein, Frederic, Reindollar, Robert, Riera, Andre, Rivera Acosta, Jose, Robaeys, Geert, Roberts, Stuart, Rodriguez-Perez, Federico, Romero-Gomez, Manuel, Rubin, Raymond, Rumi, Mariagrazia, Rushbrook, Simon, Rust, Christian, Ryan, Michael, Safadi, Rifaat, Said, Adnan, Salminen, Kimmo, Samuel, Didier, Santoro, John, Sanyal, Arun, Sarkar, Souvik, Schaeffer, Cynthia, Schattenberg, Jörn, Schiefke, Ingolf, Schiff, Eugene, Schmidt, Wolfgang, Schneider, Jeffrey, Schouten, Jeoffrey, Schultz, Michael, Sebastiani, Giada, Semela, David, Sepe, Thoma, Sheikh, Aasim, Sheikh, Muhammad, Sherman, Kenneth, Shibolet, Oren, Shiffman, Mitchell, Siddique, Asma, Sieberhagen, Cyril, Sigal, Samuel, Sikorska, Katarzyna, Simon, Krzysztof, Sinclair, Marie, Skoien, Richard, Solis, Joel, Sood, Siddharth, Souder, Bob, Spivey, Jame, Stal, Per, Stinton, Laura, Strasser, Simone, Svorcan, Petar, Szabo, Gyongzi, Talal, Andrew, Tam, Edward, Tetri, Brent, Thuluvath, Paul, Tobias, Hillel, Tomasiewicz, Krzysztof, Torres, Dawn, Trauner, Michael, Trautwein, Christian, Tsochatzis, Emanuel, Unitt, Esther, Vargas, Victor, Varkonyi, Istvan, Veitsman, Ella, Vespasiani Gentilucci, Umberto, Victor, David, Vierling, John, Vincent, Catherine, Vincze, Aron, von der Ohe, Manfred, Von Roenn, Natasha, Vuppalanchi, Raj, Waters, Michael, Watt, Kymberly, Weltman, Martin, Wieland, Amanda, Wiener, Gregory, Williams A, Alonzo, Williams J, Jeffrey, Wilson, Jason, Yataco, Maria, Yoshida, Eric, Younes, Ziad, Yuan, Liyun, Zivony, Adam, Zogg, Donald, Zoller, Heinz, Zoulim, Fabien, Zuckerman, Eli, Zuin, Massimo, and REGENERATE Study Investigators
Subjects: Male, Biopsy, Clinical Trial, Phase III, Administration, Oral, 030204 cardiovascular system & hematology, Chronic liver disease, Settore MED/04, Biomarkers/analysis, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Liver Function Tests, Non-alcoholic Fatty Liver Disease, Clinical endpoint, Medicine, 030212 general & internal medicine, 610 Medicine & health, Chenodeoxycholic Acid/administration & dosage, education.field_of_study, Liver Function Test, Research Support, Non-U.S. Gov't, Fatty liver, Obeticholic acid, NASH, OBETICHOLIC ACID, General Medicine, Middle Aged, Multicenter Study, Randomized Controlled Trial, Administration, Female, Biomarkers, Chenodeoxycholic Acid, Double-Blind Method, Humans, Human, Oral, medicine.medical_specialty, Population, Placebo, 03 medical and health sciences, Research Support, N.I.H., Extramural, Internal medicine, Journal Article, education, Intention-to-treat analysis, business.industry, Biomarker, Interim analysis, medicine.disease, Non-alcoholic Fatty Liver Disease/drug therapy, chemistry, Human medicine, business
Abstract: © 2019 Elsevier Ltd. All rights reserved., Background: Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods: In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH, non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2-F3, or F1 with at least one accompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpoints for the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2-F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings: Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1-F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2-F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1-F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation: Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes.
Published: 2019
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36. Controlled attenuation parameter for the diagnosis of steatosis in non-alcoholic fatty liver disease

Author: Grace Lai-Hung Wong, Victor de Ledinghen, Paul Cheung-Lung Choi, Julien Vergniol, Juliette Foucher, Henry Lik-Yuen Chan, Anthony W.H. Chan, Angel Mei-Ling Chim, Wassil Merrouche, Carmen Ka-Man Chan, Vincent Wai-Sun Wong, Faiza Chermak, Jean-Baptiste Hiriart, and Brigitte Le Bail
Subjects: medicine.medical_specialty, Hepatology, medicine.diagnostic_test, business.industry, Fatty liver, Gastroenterology, nutritional and metabolic diseases, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Liver biopsy, Internal medicine, medicine, 030211 gastroenterology & hepatology, Steatosis, Steatohepatitis, Metabolic syndrome, business, Hepatic fibrosis, Transient elastography, Body mass index
Abstract: Background and Aim Controlled attenuation parameter (CAP) evaluated with transient elastography (FibroScan) is a recent method for non-invasive assessment of steatosis. Its usefulness in non-alcoholic fatty liver disease (NAFLD) is unknown. We prospectively investigated the performance of CAP for the diagnosis of steatosis in NAFLD, factors associated with discordances between CAP and steatosis grades, and relationships between CAP and clinical or biological parameters. Methods All CAP examinations performed in NAFLD patients with a liver biopsy performed within 1 week of CAP measurement were included. Liver biopsies were assessed for activity and fibrosis stage, NAFLD activity score, and steatosis graded as follows: S0, steatosis 66%. Results Two hundred sixty-one patients (59% male, age 56 years) from two ethnic groups were included. No patient had steatosis 310 dB/m. Conclusion The association of CAP with steatosis, especially in patients with non-alcoholic steatohepatitis, and with elevated BMI could be useful for the diagnosis and follow-up of NAFLD patients.
Published: 2016

37. Effects of Alcohol Consumption and Metabolic Syndrome on Mortality in Patients With Nonalcoholic and Alcohol-Related Fatty Liver Disease

Author: Issah Younossi, Yuichiro Eguchi, Marlen Castellanos-Fernandez, Ajay Duseja, Georgios Papatheodoridis, Fatema Nader, Elisabetta Bugianesi, Nahum Méndez-Sánchez, Janus P. Ong, Arian Afendy, Vincent Wai-Sun Wong, Mohamed El Kassas, Maria Stepanova, Mariam Ziayee, Robert J. Wong, Yusuf Yilmaz, Aijaz Ahmed, Jacob George, Victor de Ledinghen, Ira M. Jacobson, Manuel Romero-Gómez, Lawrence Serfaty, Marco Arrese, Zobair M. Younossi, Younossi, Zobair M., Stepanova, Maria, Ong, Janus, Yilmaz, Yusuf, Duseja, Ajay, Eguchi, Yuichiro, El Kassas, Mohamed, Castellanos-Fernandez, Marlen, George, Jacob, Jacobson, Ira M., Bugianesi, Elisabetta, Wong, Vincent Wai-Sun, Arrese, Marco, de Ledinghen, Victor, Romero-Gomez, Manuel, Mendez-Sanchez, Nahum, Ahmed, Aijaz, Wong, Robert, Papatheodoridis, Georgios, Serfaty, Lawrence, Younossi, Issah, Nader, Fatema, Ziayee, Mariam, and Afendy, Arian
Subjects: Male, Alcohol, PROGRESSION, Chronic Liver Disease, STEATOHEPATITIS, chemistry.chemical_compound, Liver Cirrhosis, Alcoholic, Non-alcoholic Fatty Liver Disease, Risk Factors, FIBROSIS, Metabolic Syndrome, Incidence, Fatty liver, Hazard ratio, Diabetes, Gastroenterology, NASH, ASSOCIATION, Middle Aged, Prognosis, PREVALENCE, Survival Rate, Cohort, Disease Progression, Female, BURDEN, Adult, medicine.medical_specialty, Alcohol Drinking, UNITED-STATES, Subgroup analysis, Outcomes, National Death Index, Young Adult, Internal medicine, medicine, Humans, Aged, Retrospective Studies, Hepatology, business.industry, Alcohol Abuse, medicine.disease, United States, chemistry, Steatosis, Metabolic syndrome, business, Follow-Up Studies
Abstract: Background & Aims Non-alcoholic and alcohol-related fatty liver disease are overlapping diseases in which metabolic syndrome and alcohol consumption each contribute to progressive liver disease. We aimed to assess the effects of alcohol consumption and metabolic syndrome on mortality in individuals with fatty liver. Methods We searched the National Health and Nutrition and Examination Survey III for adults (20–74 years old) with hepatic steatosis, detected by ultrasound, for whom mortality and follow-up data were available. We collected data from the alcohol use questionnaire (self-reported number of days a participant drank alcohol; the number of drinks [10 g alcohol] per day on a drinking day; the number of days the participant had 5 or more drinks) and calculated the average amount of alcohol consumption in drinks/day for each participant during the year preceding enrollment. Excessive alcohol consumption for men was >3 drinks/day and for women was >1.5 drinks/day. We also collected clinical data, and mortality data were obtained from the National Death Index. Demographic and clinical parameters were compared among consumption groups using the χ2 test for independence or survey regression models. We used Cox proportional hazard models to identify independent predictors of all-cause and cause-specific mortality. Results The study cohort included 4264 individuals with hepatic steatosis (mean age, 45.9 years; 51% male; 76% white; 46% with metabolic syndrome; 6.2% with excessive alcohol use). There was no significant difference in mean age between individuals with vs without excessive alcohol consumption (P=.65). However, overall mortality was significantly higher among participants with excessive alcohol consumption (32.2%) vs participants with non-excessive alcohol use (22.2%) after mean 20 years of follow up (P=.003), as well as after 5 years of follow up. In multivariate analysis, the presence of metabolic syndrome (adjusted hazard ratio [aHR], 1.43; 95% CI, 1.12–1.83) and excessive alcohol consumption (aHR, 1.79; 95% CI, 1.21–2.66) were independently associated with an increased risk of death in individuals with hepatic steatosis; any lower average amount of alcohol consumption was not associated with mortality (all P>.60). In a subgroup analysis, the association of excessive alcohol use with mortality was significant in individuals with metabolic syndrome (aHR, 2.46; 95% CI, 1.40–4.32) but not without it (P=.74). Conclusion In review of data from the National Health and Nutrition and Examination Survey III, we associated alcohol consumption with increased mortality in participants with fatty liver and metabolic syndrome. These findings indicate an overlap between non-alcoholic and alcohol-related fatty liver disease.
Published: 2018

38. Unified interpretation of liver stiffness measurement by M and XL probes in non-alcoholic fatty liver disease

Author: Juliette Foucher, Brigitte Le Bail, Sally She-Ting Shu, Vincent Wai-Sun Wong, Sarah Shili, Marie Irles, Victor de Ledinghen, Wah-Kheong Chan, Henry Lik-Yuen Chan, Anthony W.H. Chan, Wassil Merrouche, and Grace Lai-Hung Wong
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Disease, Gastroenterology, Body Mass Index, Liver stiffness, Non-alcoholic Fatty Liver Disease, Internal medicine, medicine, Humans, Prospective Studies, Aged, medicine.diagnostic_test, business.industry, Fatty liver, Reproducibility of Results, Middle Aged, medicine.disease, Cross-Sectional Studies, ROC Curve, Liver biopsy, Elasticity Imaging Techniques, Female, Steatosis, Hepatic fibrosis, business, Transient elastography, Body mass index
Abstract: ObjectiveThe latest model of vibration-controlled transient elastography (VCTE) automatically selects M or XL probe according to patients’ body built. We aim to test the application of a unified interpretation of VCTE results with probes appropriate for the body mass index (BMI) and hypothesise that this approach is not affected by hepatic steatosis.DesignWe prospectively recruited 496 patients with non-alcoholic fatty liver disease who underwent VCTE by both M and XL probes within 1 week before liver biopsy.Results391 (78.8%) and 433 (87.3%) patients had reliable liver stiffness measurement (LSM) (10 successful acquisitions and IQR:median ratio ≤0.30) by M and XL probes, respectively (p2 had higher LSM regardless of the probe used. When M and XL probes were used in patients with BMI 2, respectively, they yielded nearly identical median LSM at each fibrosis stage and similar diagnostic performance. Severe steatosis did not increase LSM or the rate of false-positive diagnosis by XL probe.ConclusionHigh BMI but not severe steatosis increases LSM. The same LSM cut-offs can be used without further adjustment for steatosis when M and XL probes are used according to the appropriate BMI.
Published: 2018

39. Grazoprevir plus elbasvir in HCV genotype-1 or -4 infected patients with stage 4/5 severe chronic kidney disease is safe and effective

Author: Victor de Ledinghen, Sophie Hillaire, Emilie Bérard, Anne Minello, Maeva Guillaume, Nassim Kamar, Véronique Loustaud-Ratti, David Saadoun, Brigitte Bernard-Chabert, Valérie Canva, Isabelle Ollivier-Hourmand, Laurent Alric, Vincent Leroy, Anaïs Vallet-Pichard, Marc Bourlière, Isabelle Fouchard-Hubert, Eric Nguyen-Khac, Stanislas Pol, Dominique Trias, 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), Chirurgie Générale et Digestive [Purpan], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Foch [Suresnes], 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), 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), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de Chirurgie digestive, endocrinienne et générale [CHU Limoges], CHU Limoges, Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Département d'hépato-gastroentérologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d'hépato-gastro-entérologie, Hôpital Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Hépato-Gastroentérologie, CHU Amiens-Picardie, Service d'hépato-gastroentérologie [CHU Grenoble Alpes], Centre Hospitalier Universitaire [Grenoble] (CHU), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [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)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, Centre de Physiopathologie Toulouse Purpan (CPTP), 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 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), CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Toulouse [Toulouse]-Hôpital de Rangueil, 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), 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-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), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Cochin [AP-HP]-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie du système immunitaire, Immunologie - Immunopathologie - Immunothérapie (I3), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Sustained Virologic Response, medicine.medical_treatment, 030232 urology & nephrology, Comorbidity, Hepacivirus, Severity of Illness Index, Liver disease, 0302 clinical medicine, Medicine, Aged, 80 and over, education.field_of_study, hemodialysis, Imidazoles, Middle Aged, 3. Good health, Drug Combinations, Grazoprevir, Nephrology, HCV, Female, 030211 gastroenterology & hepatology, Hemodialysis, Adult, medicine.medical_specialty, Elbasvir, Genotype, Population, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, elbasvir, 03 medical and health sciences, Quinoxalines, Internal medicine, Humans, Adverse effect, education, Aged, Benzofurans, Retrospective Studies, DAA, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, grazoprevir, Hepatitis C, Chronic, medicine.disease, Concomitant, Kidney Failure, Chronic, business, chronic kidney disease, Kidney disease
Abstract: IF 8.429 (2017); International audience; Patients with advanced chronic kidney disease who receive direct-acting antiviral drugs require special consideration regarding comorbid conditions. Here we assessed the efficacy and safety of grazoprevir plus elbasvir in 93 patients infected with HCV genotype 1 or 4 and with advanced chronic kidney disease in a non-randomized, multicenter, nationwide observational survey. Twenty patients with HCV genotype 1a, 51 patients with 1b, four unclassified genotype 1, 17 with genotype 4 and one with genotype 6 received grazoprevir plus elbasvir (100/50 mg) once daily. All patients had severe chronic kidney disease with 70 patients stage G5, including patients on hemodialysis (74.2%), and 23 were stage G4 chronic kidney disease. Severe liver disease (Metavir F3/F4) was found in 33 patients. A sustained virologic response 12 weeks after the end of therapy was achieved in 87 of 90 patients. Two patients had a virologic breakthrough and one had a relapse after treatment withdrawal. Most patients received many concomitant medications (mean 7.7) related to comorbid conditions. Serious adverse events occurred in six patients, including three deaths while on grazoprevir plus elbasvir, not related to this therapy. Thus, once-daily grazoprevir plus elbasvir was highly effective with a low rate of adverse events in this advanced chronic kidney disease difficult-to-treat population with an HCV genotype 1 or 4 infection.
Published: 2018

40. Retreatment With Sofosbuvir Plus Grazoprevir/Elbasvir Plus Ribavirin of Patients With Hepatitis C Virus Genotype 1 or 4 Who Previously Failed an NS5A- or NS3-Containing Regimen: The ANRS HC34 REVENGE Study

Author: Caroline Jezequel, Laurent Alric, Didier Samuel, Sophie Metivier, Stanislas Pol, Christophe Hézode, Christelle Tual, Severine Gibowski, Dominique Larrey, Jean-Michel Pawlotsky, Claire Laforest, Albert Tran, Eric Bellissant, Aurelie Pailhe, Victor de Ledinghen, Marc Bourlière, Alain Renault, Fabien Zoulim, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-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), 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), IMRB - VHC/'Viruses-Hepatology-Cancers' [Créteil] (U955 Inserm - UPEC), 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), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris], CHU Pontchaillou [Rennes], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, 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), CHU Toulouse [Toulouse], Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Hôpital Paul Brousse, 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), ANRS France Recherche Nord & sud Sida-hiv hépatites, Hôpital Saint-Joseph [Marseille], Université de Rennes (UR)-Hôpital Pontchaillou-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), Institut Pasteur [Paris] (IP), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-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 ), 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 Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Centre de Recherche Translationnelle ( CRT ), Pharmacochimie et Pharmacologie Pour le Développement ( PHARMA-DEV ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique ( CNRS ), CHU Saint-Eloi-Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), CHU Purpan, Centre méditérannéen de médecine moléculaire ( C3M ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Translationnelle (CRT), 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), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Inserm, UMR-1053, Université de Bordeaux, Bordeaux, F-33076, France, Département d'hépatologie et de gastroentérologie [CHU Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], Université Toulouse III - Paul Sabatier (UT3), 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-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Cyclopropanes, Male, Sofosbuvir, Sustained Virologic Response, Hepacivirus, medicine.disease_cause, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, grazoprevir/elbasvir, Prospective Studies, Treatment Failure, Sulfonamides, Imidazoles, virus diseases, Hepatitis C, Middle Aged, 3. Good health, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious Diseases, Grazoprevir, Retreatment, RNA, Viral, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.drug, Microbiology (medical), Elbasvir, medicine.medical_specialty, Genotype, Hepatitis C virus, Antiviral Agents, sofosbuvir, 03 medical and health sciences, Internal medicine, Quinoxalines, Ribavirin, medicine, Humans, NS5A, Aged, Benzofurans, DAA, business.industry, [ SDV.SP.PHARMA ] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Chronic, medicine.disease, Virology, Amides, digestive system diseases, Regimen, 030104 developmental biology, chemistry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Carbamates, hepatitis C, business, RAS
Abstract: International audience; Background: Failure to achieve sustained virological response (SVR) with hepatitis C virus (HCV) direct-acting antiviral (DAA)–based regimens is commonly associated with emergence of resistance-associated substitutions (RASs). Retreatment of patients who failed prior DAAs remains challenging. The aim of this prospective and randomized study was to evaluate the efficacy (primary endpoint: SVR 12 weeks after end of treatment [SVR12]) and safety of sofosbuvir + grazoprevir/elbasvir + ribavirin for 16 or 24 weeks in patients who had failed to achieve SVR on previous NS5A- or NS3-based therapy and with evidence of RASs at failure.Methods: Patients were chronically infected with HCV genotype 1 or 4. Most of them had advanced fibrosis or compensated cirrhosis (liver stiffness 5.8–48.8 kPa).Results: All patients achieved HCV RNA below the lower limit of quantification (either target detected [unquantifiable] or target not detected) during treatment. SVR12 was achieved by 25 of 26 patients. The only patient who did not reach SVR was a patient who died, but HCV RNA was negative at this time (5 weeks after stopping treatment). No patient discontinued treatment because of adverse events or virological failure. Globally, treatment was well tolerated.Conclusions: Our findings support the concept of retreating with sofosbuvir + grazoprevir/elbasvir + ribavirin, for 16 weeks, genotype 1 or 4 DAA-experienced patients with proven NS5A or NS3 RASs.
Published: 2018

41. Non-invasive prediction of esophageal varices by stiffness and platelet in non-alcoholic fatty liver disease cirrhosis

Author: Marco Barbara, Giada Sebastiani, Anna Ludovica Fracanzani, Vito Di Marco, Salvatore Petta, Vincent Wai-Sun Wong, Mauro Viganò, Antonio Craxì, Quentin M. Anstee, Vincenza Calvaruso, Calogero Cammà, Fabio Marra, Annalisa Berzigotti, Victor de Ledinghen, Elisabetta Bugianesi, Petta, Salvatore, Sebastiani, Giada, Bugianesi, Elisabetta, Viganò, Mauro, Wong, Vincent Wai-Sun, Berzigotti, Annalisa, Fracanzani, Anna Ludovica, Anstee, Quentin M., Marra, Fabio, Barbara, Marco, Calvaruso, Vincenza, Cammà, Calogero, Di Marco, Vito, Craxì, Antonio, and de Ledinghen, Victor
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Alcoholic liver disease, Cirrhosis, Varice, Esophageal and Gastric Varices, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Esophageal varices, Baveno, NAFLD, Stiffness, Varices, Aged, Cross-Sectional Studies, Elasticity Imaging Techniques, Endoscopy, Digestive System, Female, Humans, Middle Aged, Non-alcoholic Fatty Liver Disease, Platelet Count, Internal medicine, medicine, Screening procedures, Cirrhosi, medicine.diagnostic_test, Hepatology, Esophagogastroduodenoscopy, business.industry, Fatty liver, medicine.disease, 3. Good health, 030220 oncology & carcinogenesis, Stiffne, 030211 gastroenterology & hepatology, business
Abstract: Background & Aims: Baveno VI and expanded Baveno VI criteria can avoid the need for esophagogastroduodenoscopy (EGD) to screen for varices needing treatment (VNT) in a substantial proportion of compensated patients with viral and/or alcoholic cirrhosis. This multicenter, cross-sectional study aims to validate these criteria in patients with compensated cirrhosis due to non-alcoholic fatty liver disease (NAFLD), accounting for possible differences in liver stiffness measurement (LSM) values between M and XL probes. Methods: We assessed 790 patients with NAFLD-related compensated cirrhosis who had EGD within six months of a reliable LSM, measured by FibroScan® using M and/or XL probe. Baveno VI and expanded Baveno VI criteria were tested. The main variable used to optimize criteria was the percentage of endoscopies spared, keeping the risk of missing large VNT below a 5% threshold. Results: LSM was measured by both M and XL probes (training set) in 314 patients, while only M or XL probe (validation sets) were used to measure LSM in 338 and 138 patients, respectively. In the training set, use of Baveno VI and expanded Baveno VI criteria reduced the number of EGD by 33.3% and by 58%, with 0.9% and 3.8% of large esophageal varices missed, respectively. The best thresholds to rule-out VNT were identified as platelet count >110,000/mm3 and LSM 110,000/mm3 and LSM
Published: 2018

42. Efficacy of Elbasvir and Grazoprevir in Participants with Hepatitis C Virus Genotype 4 Infection: A Pooled Analysis

Author: Janice Wahl, Tarik Asselah, Hendrik W. Reesink, Bach-Yen Nguyen, Ernest Asante-Appiah, Michael N. Robertson, Peggy Hwang, Victor de Ledinghen, Eliav Barr, Lawrence Serfaty, Rohit Talwani, Paul J. Pockros, Jan Gerstoft, and Other departments
Subjects: Adult, Cyclopropanes, Liver Cirrhosis, Male, medicine.medical_specialty, Elbasvir, Internationality, Genotype, Sustained Virologic Response, Population, Hepacivirus, Antiviral Agents, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Quinoxalines, Internal medicine, Drug Resistance, Viral, Ribavirin, medicine, Clinical endpoint, Humans, 030212 general & internal medicine, NS5A, education, Aged, Benzofurans, Sulfonamides, education.field_of_study, Hepatology, business.industry, Imidazoles, virus diseases, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, Amides, Pooled analysis, Grazoprevir, chemistry, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, Carbamates, business
Abstract: Background & aims The aim of this integrated analysis was to assess the efficacy of the once-daily combination of elbasvir 50 mg and grazoprevir 100 mg, with and without ribavirin in HCV genotype 4 (GT4)-infected participants enrolled in the Phase 2/3 clinical programme with elbasvir/grazoprevir. Methods Treatment-naive and treatment-experienced participants 18 years of age or older with chronic HCV GT4 infection and baseline HCV RNA ≥10 000 IU/mL were included in the analysis. The analysis population was the full analysis set (FAS; all participants who received at least 1 dose of study medication) and a total of 155 HCV GT4 participants were evaluated. The primary endpoint was sustained virologic response at week 12 (SVR12; HCV RNA less than the lower limit of quantitation at 12 weeks after the completion of study therapy). Results Overall, among GT4-infected participants treated with 12 or 16 weeks of elbasvir/grazoprevir ± ribavirin, the SVR12 efficacy rates were 96.4% (107/111) in treatment-naive participants and 88.6% (39/44) in treatment-experienced participants. The SVR12 rates were 96.0% (97/101) in treatment-naive participants treated with 12 weeks of elbasvir/grazoprevir and 100% (8/8) in treatment-experienced participants treated with 16 weeks of elbasvir/grazoprevir plus ribavirin. Efficacy was not impacted by GT4 subtype. Conclusions The regimens of 12 weeks of elbasvir/grazoprevir without ribavirin, and 16 weeks of elbasvir/grazoprevir plus ribavirin, were efficacious in HCV GT4-infected treatment-naive and treatment-experienced participants respectively. Baseline NS5A resistance-associated substitutions did not impact the efficacy of elbasvir/grazoprevir in GT4-infected participants.
Published: 2018

43. Effectiveness and safety of anti-TNF therapy for inflammatory bowel disease in liver transplant recipients for primary sclerosing cholangitis: A nationwide case series

Author: David Laharie, Sébastien Dharancy, Maria Nachury, Sylvie Radenne, Laurent Peyrin-Biroulet, Vincent Leroy, Roman Combes, Christophe Duvoux, François Durand, Filomena Conti, Georges-Philippe Pageaux, Jérôme Dumortier, Lucile Boivineau, Xavier Treton, Romain Altwegg, Felix Goutorbe, Victor de Ledinghen, Olivier Chazouillères, Géraldine Lamblin, Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Université de Montpellier (UM)-CHU Saint-Eloi, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Service d'hépatologie [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), 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), Hôpital Edouard Herriot [CHU - HCL], Service d'hépato-gastroentérologie [CHU Grenoble Alpes], Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépato-gastroentérologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Claude Huriez [Lille], CHU Lille, CHU Clermont-Ferrand, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], and Centre Hospitalier Universitaire [Grenoble] (CHU)
Subjects: Male, Colorectal cancer, Cholangitis, medicine.medical_treatment, Anti-TNF alpha, [SDV]Life Sciences [q-bio], 030230 surgery, Liver transplantation, Gastroenterology, Inflammatory bowel disease, Sclerosing, 0302 clinical medicine, Adrenal Cortex Hormones, Medicine, Remission Induction, Colonoscopy, Middle Aged, Ulcerative colitis, 3. Good health, Combination, Disease Progression, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, France, Colorectal Neoplasms, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Cholangitis, Sclerosing, Tacrolimus, Primary sclerosing cholangitis, 03 medical and health sciences, Young Adult, Drug Therapy, Internal medicine, Adalimumab, Humans, Retrospective Studies, Hepatology, business.industry, Tumor Necrosis Factor-alpha, medicine.disease, Inflammatory Bowel Diseases, Infliximab, digestive system diseases, Liver Transplantation, business
Abstract: International audience; BACKGROUND: There is a lack of consensus regarding the treatment of inflammatory bowel disease (IBD) after liver transplantation (LT) forprimary sclerosing cholangitis (PSC). AIM: To investigate the safety and effectiveness of anti-TNF therapy in patients with IBD after a LT for PSC. METHODS: We reviewed the medical files of all of the IBD patients who underwent a LT for PSC and who were treated with anti-TNF therapy at 23 French liver transplantation centers between 1989 and 2012. RESULTS: Eighteen patients (12 with ulcerative colitis and 6 who had Crohn's disease) were recruited at 9 LT centers. All of these patients received infliximab or adalimumab following their LT, and the median duration of their anti-TNF treatment was 10.4 months. The most frequent concomitant immunosuppressive treatment comprised a combination of tacrolimus and corticosteroids. Following anti-TNF therapy induction, a clinical response was seen in 16/18 patients (89%) and clinical remission in 10 (56%). At the end of the anti-TNF treatment or at the last follow-up examination (the median follow-up was 20.9 months), a clinical response was achieved in 12 patients (67%) and clinical remission in 7 (39%). A significant endoscopic improvement was observed in 9 out of 14 patients and a complete mucosal healing in 3 out of 14 patients (21%). Six patients experienced a severe infection. These were due to cholangitis, cytomegalovirus (CMV) infection, Clostridium difficile, cryptosporidiosis, or Enterococcus faecalis. Three patients developed colorectal cancer after LT, and two patients died during the follow-up period. CONCLUSIONS: Anti-TNF therapy proved to be effective for treating IBD after LT for PSC. However, as 17% of the patients developed colorectal cancer during the follow-up, colonoscopic annual surveillance is recommended after LT, as specified in the current guidelines.
Published: 2018

44. 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

45. J Pediatr Gastroenterol Nutr

Author: Anne-Laure Gominon, Michael Fayon, Julien Vergniol, H. Clouzeau, Stéphanie Bui, Thierry Lamireau, Raphaël Enaud, Eric Frison, Victor de Ledinghen, Jean-Baptiste Hiriart, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, medicine.medical_specialty, Adolescent, Cystic Fibrosis, Cystic fibrosis, Gastroenterology, LEHA, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Interquartile range, Internal medicine, medicine, Humans, In patient, Stage (cooking), Child, Retrospective Studies, business.industry, Liver Diseases, Ultrasound, Infant, Retrospective cohort study, medicine.disease, 3. Good health, Child, Preschool, USMR, Pediatrics, Perinatology and Child Health, Disease Progression, Linear Models, Elasticity Imaging Techniques, 030211 gastroenterology & hepatology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Transient elastography, Follow-Up Studies
Abstract: Objectives Cystic fibrosis-related liver disease (CFLD) can develop silently in early life and approximately 10% of children with cystic fibrosis (CF) become cirrhotic before adulthood. Clinical, biological, and ultrasound criteria used to define CFLD often reveal liver involvement at an advanced stage. The aim of this retrospective study was to assess the progression of liver stiffness measurement (LSM) in pediatric patients with CF. Methods The change of LSM, expressed as kPa/year and %/year, was measured using transient elastography (Fibroscan) in 82 children with CF (median age: 6.8 years, interquartile range [IQR]: 5.8). Mean time interval between the 2 LSM was 3.5 years. Results Median initial liver stiffness was 3.7 kPa (IQR: 1.3), and then progressed by 0.23 kPa/year, that is, 6%/year. The 7 patients who developed CFLD had a higher initial level of alanine aminotransferase (50 [IQR: 15] vs 30 [IQR: 18], P = 0.0001) and presented a more rapid progression of LSM (0.94 vs 0.23 kPa/year, P = 0.02). Conclusions The present study shows that the slope of worsening of liver stiffness is greater in patients who will develop CFLD, suggesting that annual transient elastography may be useful to detect risk of severe liver disease at an earlier stage.
Published: 2018

46. Non-invasive diagnosis of liver fibrosis in patients with alcohol-related liver disease by transient elastography: an individual patient data meta-analysis

Author: Sebastian Mueller, Christophe Moreno, Sylvie Naveau, Aleksander Krag, Cosmin Sebastian Voican, Pierre Nahon, Marianne Ziol, Bjørn Stæhr Madsen, Eric Nguyen-Khac, Maja Thiele, Momar Diouf, Victor de Ledinghen, Gabriel Perlemuter, Jérôme Boursier, Sang Gyune Kim, Denis Chatelain, Peter Stärkel, M. Fernandez, Service d'Hépato-gastroentérologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Service d'hépato-gastro-entérologie et nutrition, AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cytokines, chimiokines et immunopathologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), 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), Université libre de Bruxelles (ULB), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Institut de Mathématiques de Marseille (I2M), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), Centre d'investigation de la fibrose hépatique [CHU de Bordeaux] (Hôpital Haut-Lévêque ), Hôpital Haut-Lévêque [CHU de Bordeaux], Gastroenterology, St. Luc University Hospital, Hôpital Antoine Béclère, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Department of Internal Medicine, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (USPC), Hôpital Jean Verdier [AP-HP], Université de Picardie Jules Verne (UPJV), Direction de la recherche clinique et de l'innovation [CHU Amiens], Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), and Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Adult, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Alcoholic hepatitis, Asymptomatic, Gastroenterology, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Fibrosis, Liver Cirrhosis, Alcoholic, Internal medicine, medicine, Humans, Aspartate Aminotransferases, Aged, Hepatitis, Hepatology, medicine.diagnostic_test, business.industry, Hepatitis, Alcoholic, Bilirubin, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, 3. Good health, Liver, 030220 oncology & carcinogenesis, Liver biopsy, Asymptomatic Diseases, Elasticity Imaging Techniques, 030211 gastroenterology & hepatology, Female, medicine.symptom, business, Transient elastography
Abstract: International audience; BACKGROUND: The value of transient elastography for the non-invasive diagnosis of alcohol-related liver fibrosis is subject to debate. We did an individual patient data (IPD) meta-analysis to determine specific diagnostic cutoff values for liver stiffness in alcohol-related fibrosis, and to assess the effect of aminotransferase concentrations, bilirubin concentrations, and presence of asymptomatic and non-severe alcoholic hepatitis on liver stiffness.METHODS: We searched for studies that included patients with alcohol-related liver disease, liver biopsy, and transient elastography, and with a statistical method for determining the diagnostic cutoffs for alcohol-induced liver fibrosis on the basis of the FibroScan results, in PubMed between Jan 1, 2000, and Sept 30, 2017. Native data bases were obtained from corresponding authors in an Excel form. Pooled diagnostic cutoffs for the various fibrosis stages were determined in a two-stage, random-effects meta-analysis. The effects of aspartate aminotransferase (AST) concentrations, bilirubin concentrations, and histological features of asymptomatic and non-severe alcoholic hepatitis on liver stiffness cutoff were assessed in one-stage, random-effects meta-analysis.FINDINGS: Of 188 studies assessed, ten studies comprising 1026 patients were included in the meta-analysis, yielded liver stiffness cutoffs of 7·0 kPa (area under the receiver operating characteristic curve 0·83 [SE 0·02; 95% CI 0·79-0·87]) for F≥1 fibrosis, 9·0 kPa (0·86 [0·02; 0·82-0·90]) for F≥2, 12·1 kPa (0·90 [0·02; 0·86-0·94]) for F≥3, and 18·6 kPa (0·91 [0·04; 0·83-0·99]) for F=4. AST and bilirubin concentrations had a significant effect on liver stiffness, with higher concentrations associated with higher liver stiffness values (pINTERPRETATION: This IPD meta-analysis highlights the link between liver stiffness and the histological features of asymptomatic and non-severe alcoholic hepatitis, reflected by AST and bilirubin concentrations. In alcohol-related liver disease, FibroScan assessments of liver fibrosis should take into account AST and bilirubin concentrations through the use of specifically adjusted liver stiffness cutoffs.FUNDING: None.
Published: 2018

47. SAT-288-Liver stiffness measurement predicts long-term survival and complications in non-alcoholic fatty liver disease

Author: Sally She-Ting Shu, Pierre-Henri Bernard, Vincent Wai-Sun Wong, Juliette Foucher, Victor de Ledinghen, Merrouche Wassil, Grace Lai-Hung Wong, Hiriart Jean-Baptiste, Ken Liu, Henry C. B. Chan, Sarah Shili, Faiza Chermak, Terry Cf Yip, and Yee-Kit Tse
Subjects: medicine.medical_specialty, Hepatology, Liver stiffness, business.industry, Internal medicine, Long term survival, Fatty liver, medicine, Non alcoholic, Disease, business, medicine.disease, Gastroenterology
Published: 2019

48. SAT-021-How to use platelets and liver stiffness to rule out esophageal varices needing treatment?

Author: Annalisa Berzigotti, Horia Stefanescu, Oana Farcau, Davide Festi, Federico Ravaioli, Victor de Ledinghen, Nathalie Ganne-Carrié, Arthur Berger, Paul Calès, and Bureau christophe
Subjects: medicine.medical_specialty, Esophageal varices, Hepatology, Liver stiffness, business.industry, Internal medicine, medicine, Platelet, medicine.disease, business, Gastroenterology
Published: 2019

49. THU-340-Epidemiology of NAFLD and advanced fibrosis in the French general population: A population-based cohort study in 118, 664 subjects (NASH-CO study)

Author: Lawrence Serfaty, Karine Lacombe, Oumarou Nabi, Philippe Mathurin, Marie Zins, Jérôme Boursier, Victor de Ledinghen, and Marcel Goldberg
Subjects: medicine.medical_specialty, Population based cohort, education.field_of_study, Hepatology, business.industry, Internal medicine, Population, Epidemiology, medicine, business, education, Advanced fibrosis
Published: 2019

50. Daclatasvir and asunaprevir plus peginterferon alfa and ribavirin in HCV genotype 1 or 4 non-responders

Author: Gregory T. Everson, David I. Bernstein, Magdy Elkhashab, Victor de Ledinghen, Stefan Zeuzem, Christophe Hézode, Lawrence Serfaty, Maurizia Rossana Brunetto, Stephanie Noviello, Eric Hughes, Albert Tran, Jeong Heo, Delphine Hennicken, Patricia Mendez, Donald M. Jensen, Kenneth E. Sherman, Fiona McPhee, Stefan Mauss, Ziad Younes, Stanislas Pol, John M. Vierling, Velimir A. Luketic, and Marcelo Kugelmas
Subjects: Adult, Male, Simeprevir, medicine.medical_specialty, Pyrrolidines, Daclatasvir, Genotype, Sofosbuvir, Peginterferon-alfa, Hepacivirus, Antiviral Agents, Gastroenterology, Drug Administration Schedule, Polyethylene Glycols, Young Adult, chemistry.chemical_compound, Pegylated interferon, Internal medicine, Ribavirin, medicine, Humans, Aged, Drug Carriers, Sulfonamides, Hepatology, business.industry, Imidazoles, Interferon-alpha, virus diseases, Valine, Hepatitis C, Chronic, Middle Aged, Viral Load, Isoquinolines, Recombinant Proteins, digestive system diseases, Treatment Outcome, chemistry, Tolerability, DNA, Viral, Immunology, Asunaprevir, Drug Therapy, Combination, Female, Carbamates, business, Follow-Up Studies, medicine.drug
Abstract: Background & Aims Improved therapies for peginterferon/ribavirin null or partial responders are needed. This study evaluated daclatasvir (NS5A inhibitor) and asunaprevir (NS3 protease inhibitor) plus peginterferon alfa-2a and ribavirin in this patient population. Methods This open-label, phase 3 study (HALLMARK-QUAD; NCT01573351) treated patients with chronic hepatitis C virus (HCV) genotype 1 (n=354) or 4 (n=44) infection who had a prior null or partial response to peginterferon/ribavirin. Patients received daclatasvir 60mg once-daily plus asunaprevir 100mg twice-daily, with weekly peginterferon alfa-2a and weight-based ribavirin for 24weeks. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12) among genotype 1-infected patients. Results Daclatasvir plus asunaprevir and peginterferon/ribavirin demonstrated SVR12 rates of 93% (95% CI 90–96) in prior non-responders infected with HCV genotype 1. SVR12 rates among genotype 4-infected patients were 98% (95% CI 93–100); one patient had a missing post-treatment week-12 HCV-RNA measurement, but achieved an SVR at post-treatment week 24, yielding a 100% SVR rate in genotype 4 patients. Prior peginterferon/ribavirin response, sex, age, IL28B genotype, or cirrhosis status did not influence SVR12 rates. Serious adverse events occurred in 6% of patients; 5% discontinued treatment due to an adverse event. Grade 3/4 laboratory abnormalities included neutropenia (22%), lymphopenia (16%), anemia (6%), thrombocytopenia (4%), and ALT/AST elevations (3% each). Conclusions Daclatasvir plus asunaprevir and peginterferon/ribavirin demonstrated high rates of SVR12 in genotype 1- or 4-infected prior null or partial responders. The combination was well tolerated and no additional safety and tolerability concerns were observed compared with peginterferon/ribavirin regimens.
Published: 2015

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