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1. Clinical outcomes after treatment with direct antiviral agents: beyond the virological response in patients with previous HCV-related decompensated cirrhosis

Author

Georges-Philippe Pageaux, Clovis Lusivika Nzinga, Nathalie Ganne, Didier Samuel, Céline Dorival, Fabien Zoulim, Carole Cagnot, Thomas Decaens, Dominique Thabut, Tarik Asselah, Philippe Mathurin, François Habersetzer, Jean-Pierre Bronowicki, Dominique Guyader, Isabelle Rosa, Vincent Leroy, Olivier Chazouilleres, Victor de Ledinghen, Marc Bourliere, Xavier Causse, Paul Cales, Sophie Metivier, Véronique Loustaud-Ratti, Ghassan Riachi, Laurent Alric, Moana Gelu-Simeon, Anne Minello, Jérôme Gournay, Claire Geist, Albert Tran, Armand Abergel, Isabelle Portal, Louis d’Alteroche, François Raffi, Hélène Fontaine, Fabrice Carrat, Stanislas Pol, and For the French ANRS CO22 Hepather Cohort

Subjects
Hepatitis C virus, Decompensated cirrhosis, Direst-acting antiviral agents, Survival, Hepatocellular carcinoma, Sustained virological response, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background In HCV-infected patients with advanced liver disease, the direct antiviral agents-associated clinical benefits remain debated. We compared the clinical outcome of patients with a previous history of decompensated cirrhosis following treatment or not with direct antiviral agents from the French ANRS CO22 HEPATHER cohort. Methods We identified HCV patients who had experienced an episode of decompensated cirrhosis. Study outcomes were all-cause mortality, liver-related or non-liver-related deaths, hepatocellular carcinoma, liver transplantation. Secondary study outcomes were sustained virological response and its clinical benefits. Results 559 patients met the identification criteria, of which 483 received direct antiviral agents and 76 remained untreated after inclusion in the cohort. The median follow-up time was 39.7 (IQR: 22.7–51) months. After adjustment for multivariate analysis, exposure to direct antiviral agents was associated with a decrease in all-cause mortality (HR 0.45, 95% CI 0.24–0.84, p = 0.01) and non-liver-related death (HR 0.26, 95% CI 0.08–0.82, p = 0.02), and was not associated with liver-related death, decrease in hepatocellular carcinoma and need for liver transplantation. The sustained virological response was 88%. According to adjusted multivariable analysis, sustained virological response achievement was associated with a decrease in all-cause mortality (HR 0.29, 95% CI 0.15–0.54, p

Published
2022
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2. Multidisciplinary approach for the treatment of 1155 HCV/HCV-HIV co-infected patients

Author

Isabelle Ravaux, Albert Darque, Amélie Ménard, Catherine Dhiver, Philippe Halfon, Thierry Allègre, Patrick Philibert, Christelle Tomei, Philippe Colson, Rolande Cohen, Laurence Pellissier, Sylvie Brégigeon, Malika Mokhtari, Jacques Moreau, Marie-Josephe Soavi, Caroline Solas, Isabelle Poizot-Martin, Bernard Castan, Valérie Oulès, Marc Bourlière, Isabelle Portal, and Danielle Botta-Fridlund

Subjects
Microbiology, QR1-502, Public aspects of medicine, RA1-1270
Published
2016
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3. 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
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4. 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
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5. Hepatitis B virus reactivation in HBsAg-negative patients is associated with emergence of viral strains with mutated HBsAg and reverse transcriptase

Author

Anne Motte, Catherine Tamalet, René Gerolami, D. Botta-Fridlund, Aude Charbonnier, Patrick Borentain, Julie Bertrand, Diane Coso, Jacques Serratrice, Isabelle Portal, Thérèse Aurran-Schleinitz, Anne-Marie Stoppa, Fabrice Barlesi, Mélanie Serrero, Christian Chabannon, and Philippe Colson

Subjects
Adult, Male, Hepatitis B virus, HBsAg, Hepatitis B virus DNA polymerase, Antineoplastic Agents, Biology, medicine.disease_cause, Hepatitis B virus PRE beta, Serology, Neoplasms, Virology, HBV therapy, medicine, Chemotherapy, Humans, HBV-DNA detection, Aged, Hepatitis B virus reactivation, Hepatitis B Surface Antigens, Nucleoside analogue, virus diseases, RNA-Directed DNA Polymerase, Middle Aged, Resistance mutation, digestive system diseases, Reverse transcriptase, Female, Mutant Proteins, Virus Activation, medicine.drug
Abstract

Background/aims Virological factors associated with hepatitis B virus reactivation (HBV-R), following chemotherapy for cancer in hepatitis B surface antigen (HBsAg)-negative patients, are not well known. Materials and methods HBV strains from 16 patients presenting HBV-R following chemotherapy were studied and compared to those obtained from 51 HBV chronically-infected patients. Results HBsAg variability was significantly increased within the major hydrophilic region, the a determinant and the C-terminal region. Amino acid substitutions were more frequently found in HBV-R patients as compared to controls at 17 and 11 positions within HBsAg and HBV-RT, respectively. This resulted in atypical serological testing in 56% of patients and detection of resistance mutation to nucleoside analogs in 12.5%. Conclusion HBsAg and HBV-RT mutations are frequently encountered in patients with HBV-R, resulting in atypical serological testing and emergence of HBV strains resistant to nucleos(t)ides analogs.

Published
2015
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6. Hepatitis C virus NS3 protease genotyping and drug concentration determination during triple therapy with telaprevir or boceprevir for chronic infection with genotype 1 viruses, southeastern France

Author

Saadia Mokhtari, Jean-Marie Ruiz, Catherine Tamalet, Caroline Solas, Isabelle Portal, Philippe Brouqui, Sarah Aherfi, Anne Motte, Isabelle Ravaux, Sylvie Bregigeon, Andreas Stein, Catherine Dhiver, René Gerolami, Philippe Colson, Isabelle Poizot-Martin, Jacques Moreau, Patrick Borentain, and Danielle Botta-Fridlund

Subjects
education.field_of_study, business.industry, Ribavirin, Hepatitis C virus, Population, virus diseases, medicine.disease_cause, Virology, digestive system diseases, Telaprevir, chemistry.chemical_compound, Infectious Diseases, chemistry, Pegylated interferon, Boceprevir, Medicine, Protease inhibitor (pharmacology), education, business, Viral load, medicine.drug
Abstract

Telaprevir and boceprevir, the two first hepatitis C virus (HCV) NS3 protease inhibitors (PIs), considerably increase rates of sustained virologic response in association with pegylated interferon and ribavirin in chronic HCV genotype 1 infections. The 30 first patients treated by telaprevir or boceprevir including anti-HCV therapies since 2011 in Marseille University hospitals, France, were monitored. HCV loads and plasmatic concentrations of telaprevir and boceprevir were determined on sequential blood samples. HCV NS3 protease gene population sequencing was performed at baseline of treatment and in case of treatment failure. Fifteen patients (including 7 co-infected with HIV) received telaprevir and the other 15 patients (including 4 co-infected with HIV) received boceprevir. At baseline, HCV NS3 protease from six patients harbored amino acid substitutions associated with PI-resistance. Treatment failure occurred at week 12 for 7 patients. Amino acid substitutions associated with PI-resistance were observed in six of these cases. HCV NS3 R155K and T54A/S mutants, all of genotype 1a, were found from four patients. Median (interquartile range) plasma concentrations were 3,092 ng/ml (2,320-3,525) for telaprevir and 486 ng/ml (265-619) for boceprevir. For HIV-HCV co-infected patients, median concentrations were 3,162 ng/ml (2,270-4,232) for telaprevir and 374 ng/ml (229-519) for boceprevir. Plasma drug concentration monitoring revealed undetectable concentrations for two patients at week 4, and probable non-adherence to therapy for another patient. These findings indicate that routine HCV NS3 protease sequencing and plasma PI concentration monitoring might be helpful to characterize cases of therapy failure, at a cost dramatically low compared to that of anti-HCV therapy.

Published
2014
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7. Multidisciplinary approach for the treatment of 1155 HCV/HCV-HIV co-infected patients

Author

Laurence Pellissier, Caroline Solas, Malika Mokhtari, Danielle Botta-Fridlund, B. Castan, M. Soavi, Rolande Cohen, Sylvie Bregigeon, Philippe Halfon, Catherine Dhiver, Isabelle Portal, Christelle Tomei, Albert Darque, Thierry Allegre, Isabelle Poizot-Martin, Patrick Philibert, Amélie Menard, Isabelle Ravaux, Jacques Moreau, Valérie Oules, Marc Bourlière, and Philippe Colson

Subjects
medicine.medical_specialty, Epidemiology, business.industry, Immunology, Public Health, Environmental and Occupational Health, Human immunodeficiency virus (HIV), medicine.disease_cause, Microbiology, QR1-502, Infectious Diseases, Multidisciplinary approach, Virology, Internal medicine, medicine, Public aspects of medicine, RA1-1270, business
Published
2016

8. A single IL28B genotype SNP rs12979860 determination predicts treatment response in patients with chronic hepatitis C Genotype 1 virus

Author

Valérie Oules, Philippe Halfon, Danielle Botta, Albert Tran, Marc Bourlière, Isabelle Portal, Yaakov Maor, Christophe Renou, Laurent Argiro, Claire Wartelle, Paul Castellani, Guillaume Penaranda, Alain Dessein, and Denis Ouzan

Subjects
Adult, Male, medicine.medical_specialty, Genotype, Hepatitis C virus, Hepacivirus, Alpha interferon, medicine.disease_cause, Bioinformatics, Antiviral Agents, Polymorphism, Single Nucleotide, Gastroenterology, Cohort Studies, chemistry.chemical_compound, Gene Frequency, Internal medicine, Ribavirin, Humans, Medicine, Allele frequency, Hepatology, biology, business.industry, Interleukins, Interferon-alpha, virus diseases, Odds ratio, Hepatitis C, Chronic, Middle Aged, Viral Load, Prognosis, biology.organism_classification, digestive system diseases, Treatment Outcome, chemistry, Drug Therapy, Combination, Female, Interferons, business, Viral load
Abstract

BACKGROUND: Recent studies have suggested that host genetics may be useful for predicting drug response and have supported the recommendation that single polynucleotide polymorphisms (SNPs) of IL28B should be investigated when treating hepatitis C virus (HCV)-1 infected patients. The aim of this study was to determine whether a single IL-28B genotype SNP rs8099917 or rs12979860 determination is sufficient to predict treatment failure in patients with chronic HCV. METHODS: A total of 198 patients were included; mean (±standard deviation) age was 47±12 years and 140 (71%) were men. One hundred and fifty-six (79%) patients were infected with HCV genotype 1 and 42 (21%) with HCV genotypes 2 or 3. One hundred and eight (55%) patients had sustained virologic response (SVR). Two SNPs in the IL-28B were analyzed (rs8099917 and rs12979860). RESULTS: A total of 115 (58%) patients had rs8099917 TT genotype and 61 (31%) had rs12979860 CC genotype. Rs8099917 TT and rs12979860 CC genotypes were associated with SVR in HCV genotype 1 patients [odds ratio=2.60 (1.36-5.00), P=0.004 and odds ratio=3.30 (1.58-6.90), P=0.03 respectively]. No association was found between SNPs and SVR in HCV genotype 2 or 3 patients. CONCLUSION: This study confirms that SNPs rs8099917 and rs12979860 used alone may be useful for predicting the outcome of HCV treatment. In a rational and cost-effective approach, determination of only one of these two SNPs is sufficient for predicting SVR. Because of the highest predictive SVR associated with rs12979860 CC compared with the rs8099917 TT (respective positive predictive value: 72% vs. 63%, P=ns), rs12979860 determination alone is sufficient for predicting interferon response.

Published
2011
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9. Sofosbuvir plus ledipasvir in combination for the treatment of hepatitis C infection

Author

Isabelle Portal, Paul Castellani, Philippe Halfon, Souad Benali, Christelle Ansaldi, Valérie Oules, Xavier Adhoute, and Marc Bourlière

Subjects
Ledipasvir, Sofosbuvir, Genotype, Hepacivirus, Hepatitis C virus, Fixed-dose combination, medicine.disease_cause, Antiviral Agents, chemistry.chemical_compound, Drug Resistance, Viral, Ribavirin, medicine, Humans, NS5A, Fluorenes, Hepatology, biology, business.industry, Gastroenterology, Hepatitis C, medicine.disease, biology.organism_classification, Virology, Drug Combinations, chemistry, Benzimidazoles, business, medicine.drug
Abstract

Sofsobuvir is the first-in-class NS5B nucleotide inhibitor to be launched as a treatment for the hepatitis C virus (HCV). Its viral potency, pan genotypic activity and high barrier to resistance make it the ideal candidate to become a backbone for several IFN-free regimens. Ledipasvir is a NS5A inhibitor with multi genotypic activity but modest barrier to resistance. The once-daily fixed-dose combination of sofosbuvir plus ledipasvir is the first-in-market single-tablet regimen for the treatment of hepatitis C infection. Recent data demonstrated that this FDC alone, or in combination with ribavirin, is able to achieve HCV cure of at least 90% or more among genotype 1,4, 5 and 6 patients. This combination appears to be suboptimal in genotype 3 patients and other direct acting antiviral combinations with sofosbuvir will help to fulfill this gap in the near future. The safety profile of the fixed dose combination is good. Resistance is not an issue with sofosbuvir but may be a significant issue with regards to ledipasvir for those rare individuals who harbor baseline HCV NS5A resistance-associated variants that conferred a high resistance level. The rational for using FDCs and the available clinical data are reviewed.

Published
2015

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

Author

Stanislas Pol, Dominique Larrey, Hélène Fontaine, Valérie Canva, A. Tran, Christophe Hézode, Armando Abergel, Yoann Barthe, Laurent Alric, Thong Dao, Pierre Attali, J.-M. Pawlotsky, Damien Lucidarme, Didier Samuel, Patrice Cacoub, S. Metivier, Thierry Poynard, Paul Calès, V. de Ledinghen, Véronique Loustaud-Ratti, M. Bourlière, Isabelle Rosa, Fabrice Carrat, Véronique Grando-Lemaire, Fabien Zoulim, V. Di Martino, C. Dufour, Ghassan Riachi, Pierre-Henri Bernard, Jean-Pierre Bronowicki, Isabelle Portal, Lawrence Serfaty, T. Fontanges, Patrick Marcellin, J.-J. Raabe, Dominique Guyader, Xavier Causse, Jean-Pierre Zarski, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de recherche sur les Ions, les MAtériaux et la Photonique (CIMAP - UMR 6252), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service d'hépatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépato-gastroentérologie, Assistance Publique - Hôpitaux de Marseille (APHM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut d'astrophysique spatiale (IAS), Université Paris-Sud - Paris 11 (UP11)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National d’Études Spatiales [Paris] (CNES), Service des maladies du foie [CHU Rennes], Centre Hospitalier Universitaire [Rennes], Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pitié-Salpêtrière [AP-HP], SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA), Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), ESIM - Déterminants Sociaux de la Santé et du Recours aux Soins (DS3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche en Cancérologie de Montpellier ( IRCM - U1194 Inserm - UM ), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Centre de recherche sur les Ions, les MAtériaux et la Photonique ( CIMAP - UMR 6252 ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Supérieure d'Ingénieurs de Caen ( ENSICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Assistance Publique - Hôpitaux de Marseille ( APHM ), Service d'hépatologie [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Institut d'astrophysique spatiale ( IAS ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ), Service des maladies du foie, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Centre Hospitalier Universitaire de Rennes, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pitié-Salpêtrière [APHP], Interactions cellulaires et applications thérapeutiques ( ICAT ), Université d'Angers ( UA ) -CHU Angers-CRLCC Paul Papin-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), CIRAD, UPR AGIRs, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Epidémiologie, Systèmes dínformation et modélisation ( ESIM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Unité de Santé Publique, Assistance publique - Hôpitaux de Paris - AP-HP (FRANCE)-CHU Saint-Antoine [APHP], Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Paris-Sud - Paris 11 (UP11)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Centre Hospitalier Universitaire [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Service d'hépatologie [CHU Saint-Antoine], Centre Hospitalier Universitaire [Rennes]-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou

Subjects
0303 health sciences, Pediatrics, medicine.medical_specialty, Hepatology, [ SDV ] Life Sciences [q-bio], business.industry, [SDV]Life Sciences [q-bio], Treatment experienced, 3. Good health, Telaprevir, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, Boceprevir, Cohort, medicine, 030211 gastroenterology & hepatology, business, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, medicine.drug
Abstract

International audience; no abstract

Published
2015
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11. Validation and comparison of indexes for fibrosis and cirrhosis prediction in chronic hepatitis C patients: proposal for a pragmatic approach classification without liver biopsies

Author

Isabelle Portal, Christophe Renou, Paul Castellani, M. A. Rosenthal-Allieri, Guillaume Penaranda, Albert Tran, L. Lecomte, Marc Bourlière, C. Degott, Denis Ouzan, Danielle Botta-Fridlund, René Gerolami, R. Deydier, and Philippe Halfon

Subjects
Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Biopsy, Hepatitis C virus, medicine.disease_cause, Gastroenterology, Cohort Studies, Fibrosis, Virology, Internal medicine, medicine, Humans, alpha-Macroglobulins, Aspartate Aminotransferases, Apolipoprotein A-I, Haptoglobins, Hepatology, medicine.diagnostic_test, Platelet Count, FibroTest, business.industry, Bilirubin, gamma-Glutamyltransferase, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, Confidence interval, Infectious Diseases, Liver, Liver biopsy, Female, business
Abstract

Noninvasive indexes have been developed to predict fibrosis staging. The aim of this study was to assess the diagnostic accuracy of these indexes in comparison with liver histology in hepatitis C virus (HCV)-infected patients. A total of 235 consecutive patients with HCV infection from the Fibropaca multicentre independent study were included in this paper. FibroTest (FT), aspartate aminotransferase to platelet ratio index (APRI) and Forns score were assessed in the cohort and compared with liver histology performed on the same day. The main end point was the area under characteristic curves (AUCs) for the diagnosis of significant fibrosis (F2-F4) and cirrhosis (F4) by the METAVIR classification. Mean age was 46 (+/-11) years, 55% were males, 42% (n = 99) had significant fibrosis (F2-F4) and 7% (n = 16) had cirrhosis (F4). For the diagnosis of significant fibrosis, respective AUCs of FT, APRI and Forns score were 0.81 (95% confidence interval: 0.76-0.86), 0.71 (0.67-0.79) and 0.76 (0.70-0.82); for cirrhosis prognosis, AUCs of FT and APRI were 0.82 (0.77-0.87) and 0.81 (0.76-0.86) (AUCs not significantly different). Using each index independently, all patients were classified by FT, 214 (91%) patients were classified by APRI and 129 (55%) by Forns score. There were significantly more cases of discordances between APRI and liver biopsy than between FT or Forns score and liver biopsy (P < 0.05). Performing all scores (FT, Forns and APRI) without liver biopsy allowed fibrosis to be well evaluated in 191 patients (81.3%), including patients with FT failure. Liver biopsy remained mandatory to evaluate fibrosis in 44 patients (18.7%). Our study shows that performing all the tests and liver biopsy improves the diagnostic accuracy for liver fibrosis in chronic hepatitis C patients without patent comorbidities. The combination of all tests with liver biopsy allowed 225/235 (96%) patients to be correctly classified. The combination of all tests without liver biopsy allowed 191/235 (81.3%) patients to be correctly classified; liver biopsy remained mandatory in some patients (18.7%).

Published
2006
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12. Independent Prospective Multicenter Validation of Biochemical Markers (Fibrotest-Actitest) for the Prediction of Liver Fibrosis and Activity in Patients with Chronic Hepatitis C: The Fibropaca Study

Author

Philippe Halfon, Marc Bourliere, Romaric Deydier, Danielle Botta-Fridlund, Christophe Renou, Albert Tran, Isabelle Portal, Isabelle Allemand, Jean Jacques Bertrand, Alessandra Rosenthal-Allieri, Michel Rotily, Christophe Sattonet, Thierry Benderitter, Marie Christine Saint Paul, Henry Pierre Bonnot, Guillaume Penaranda, Claude Degott, Marie France Masseyeff, and Denis Ouzan

Subjects
Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Adolescent, Cross-sectional study, Biopsy, Statistics as Topic, Gastroenterology, Liver Function Tests, Predictive Value of Tests, Internal medicine, medicine, Humans, alpha-Macroglobulins, In patient, Aspartate Aminotransferases, Prospective Studies, Prospective cohort study, Aged, Apolipoprotein A-I, Haptoglobins, Hepatology, medicine.diagnostic_test, business.industry, FibroTest, Alanine Transaminase, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, Cross-Sectional Studies, Liver, Predictive value of tests, Practice Guidelines as Topic, Female, Hepatic fibrosis, business, Biomarkers
Abstract

Fibrotest (FT) and Actitest (AT) are biochemical markers of fibrosis and activity for use as a non-invasive alternative to liver biopsy in patients with chronic hepatitis C virus (HCV). The aim of this study was to perform an external validation of FT and AT and to study the discordances between FT/AT and liver biopsy in patients with chronic hepatitis C.A total of 519 consecutive patients with chronic HCV were prospectively included in five centers, with liver biopsy and biochemical markers taken at the same day. Fifteen patients were excluded because their biopsies could not be interpreted. Diagnostic accuracies were assessed by receiver operating characteristic (ROC) curve analysis.Median biopsy size was 15 mm (range: 2-58), with 9 portal tracts (1-37) and 1 fragment (1-12). 46% (230/504) were classified F2-F4 in fibrosis and 39% A2-A3 in activity. FT area under ROC curve for diagnosis of activity (A2-A3), significant fibrosis (F2-F4), and severe fibrosis (F3-F4) were 0.73 [0.69-0.77], 0.79 [0.75-0.82], and 0.80 [0.76-0.83], respectively. Among the 92 patients (18%) with 2 fibrosis stages of discordance between FT and biopsy, the discordance was attributable to FT in 5% of cases, to biopsy in 4%, and undetermined in 9%.This prospective independent and multicenter study confirms the diagnostic value of FT and AT found in the princeps study and suggests that FT and AT can be an alternative to biopsy in most patients with chronic HCV.

Published
2006
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14. Daily or three times per week interferon α-2b in combination with ribavirin or interferon alone for the treatment of patients with chronic hepatitis C not responding to previous interferon alone

Author

Armand Abergel, Victor de Ledinghen, Hervé Fleury, Albert Tran, Nathalie Szostak, Pascale Trimoulet, Patrice Couzigou, Marc Bourlière, Geneviève Chêne, Pierre-Henri Bernard, Isabelle Portal, Maria Winnock, Stephane Levy, and André-Jean Remy

Subjects
Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Combination therapy, Hepatitis C virus, medicine.medical_treatment, Hepacivirus, Alpha interferon, Interferon alpha-2, medicine.disease_cause, Antiviral Agents, Gastroenterology, chemistry.chemical_compound, Interferon, Internal medicine, Ribavirin, medicine, Humans, Prospective Studies, Interferon alfa, Chemotherapy, Hepatology, biology, business.industry, Interferon-alpha, Hepatitis C, Chronic, Middle Aged, biology.organism_classification, Recombinant Proteins, Treatment Outcome, chemistry, Immunology, Drug Therapy, Combination, Female, business, medicine.drug
Abstract

We compared the efficacy and safety of the combined therapy of daily interferon alpha-2b and ribavirin with those of interferon alpha-2b three times per week alone or in combination with ribavirin in non-responder patients with hepatitis C virus (HCV) infection.A total of 376 patients were randomly assigned to receive interferon alpha-2b (6 MU three times per week for 24 weeks followed by 3 MU three times per week for 24 weeks) alone (group A) or in combination with ribavirin for 48 weeks (group B), or daily interferon alpha-2b (3 MU per day for 24 weeks followed by 3 MU three times per week for 24 weeks) and ribavirin (group C).After 24 weeks of therapy, HCV RNA was undetectable in 11.7, 24.0, and 37.8% for groups A, B, and C, respectively. Sustained virological response was more frequent in patients who received combination therapy with three times weekly interferon (20.9%) or daily interferon (26.0%) than in patients who received interferon alone (5.8%) (P0.001). The predictive HCV parameters for sustained response were a low viral load on day 7 and a negative HCV RNA on week 12.In conclusion, in non-responder patients with chronic hepatitis C, virological response with daily interferon and ribavirin, compared to interferon monotherapy, was significantly improved during treatment, although sustained virological response was similar for both combination therapies with ribavirin and three times a week or daily interferon.

Published
2002
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15. Hepatitis C virus NS3 protease genotyping and drug concentration determination during triple therapy with telaprevir or boceprevir for chronic infection with genotype 1 viruses, southeastern France

Author

Sarah, Aherfi, Caroline, Solas, Anne, Motte, Jacques, Moreau, Patrick, Borentain, Saadia, Mokhtari, Danielle, Botta-Fridlund, Catherine, Dhiver, Isabelle, Portal, Jean-Marie, Ruiz, Isabelle, Ravaux, Sylvie, Bregigeon, Isabelle, Poizot-Martin, Andreas, Stein, René, Gérolami, Philippe, Brouqui, Catherine, Tamalet, and Philippe, Colson

Subjects
Adult, Male, Genotype, Proline, Mutation, Missense, Interferon-alpha, Hepacivirus, Hepatitis C, Chronic, Middle Aged, Viral Load, Viral Nonstructural Proteins, Antiviral Agents, Hospitals, University, Plasma, Young Adult, Amino Acid Substitution, Drug Resistance, Viral, Ribavirin, Humans, Drug Therapy, Combination, Female, France, Treatment Failure, Oligopeptides
Abstract

Telaprevir and boceprevir, the two first hepatitis C virus (HCV) NS3 protease inhibitors (PIs), considerably increase rates of sustained virologic response in association with pegylated interferon and ribavirin in chronic HCV genotype 1 infections. The 30 first patients treated by telaprevir or boceprevir including anti-HCV therapies since 2011 in Marseille University hospitals, France, were monitored. HCV loads and plasmatic concentrations of telaprevir and boceprevir were determined on sequential blood samples. HCV NS3 protease gene population sequencing was performed at baseline of treatment and in case of treatment failure. Fifteen patients (including 7 co-infected with HIV) received telaprevir and the other 15 patients (including 4 co-infected with HIV) received boceprevir. At baseline, HCV NS3 protease from six patients harbored amino acid substitutions associated with PI-resistance. Treatment failure occurred at week 12 for 7 patients. Amino acid substitutions associated with PI-resistance were observed in six of these cases. HCV NS3 R155K and T54A/S mutants, all of genotype 1a, were found from four patients. Median (interquartile range) plasma concentrations were 3,092 ng/ml (2,320-3,525) for telaprevir and 486 ng/ml (265-619) for boceprevir. For HIV-HCV co-infected patients, median concentrations were 3,162 ng/ml (2,270-4,232) for telaprevir and 374 ng/ml (229-519) for boceprevir. Plasma drug concentration monitoring revealed undetectable concentrations for two patients at week 4, and probable non-adherence to therapy for another patient. These findings indicate that routine HCV NS3 protease sequencing and plasma PI concentration monitoring might be helpful to characterize cases of therapy failure, at a cost dramatically low compared to that of anti-HCV therapy.

Published
2014

16. Detection by in situ hybridization of hepatitis C virus positive and negative RNA strands using digoxigenin-labeled cRNA probes in human liver cells

Author

Marguerite Gastaldi, Richard Planells, Andrée Robaglia-Schlupp, Joëlle Fiteni, Marc Bourlière, François Quilici, Evelyne Mazzella, Isabelle Portal-Bartolomei, Pierre Cau, and Annick Massacrier

Subjects
Biopsy, Hepatitis C virus, Hepacivirus, In situ hybridization, Biology, medicine.disease_cause, Virus, RNA, Complementary, chemistry.chemical_compound, Plasmid, Image Processing, Computer-Assisted, medicine, Humans, Digoxigenin, RNA, Antisense, In Situ Hybridization, Hepatology, RNA, Virology, Molecular biology, Microscopy, Electron, Liver, chemistry, Hepatitis C Virus Positive, Cytoplasm, RNA, Viral
Abstract

In situ hybridization was performed using cRNA probes on human liver biopsies to localize both positive and negative RNA strands of hepatitis C virus. From the 5' non-coding region of the viral genome, 210 bp, were amplified by reverse transcriptase-polymerase chain reaction and cloned in a plasmid. Probes were produced by in vitro transcription, and labeled using digoxigenin-11-UTP. Positive HCV-RNA strands were detected in all 20 of the patients analyzed, whereas negative strands were detected in only nine patients, as confirmed using computerized image analysis. Both probes labeled the cytoplasm of hepatocytes with a perinuclear intensification. Few of the mononuclear cells infiltrating the portal connective space contained positive HCV-RNA strands only. Stacks of dilated endoplasmic reticulum cisternae were observed by electron microscopy and their relationship with the infection was discussed. This study confirmed that non-radioactive in situ hybridization represents a useful tool to analyze the localization and replication of hepatitis C virus in liver tissue.

Published
1995
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17. Chronic hepatitis C: treatments of the future

Author

Xavier Adhoute, Souad Benali, Valérie Oules, Isabelle Portal, Asma Khaloun, Claire Wartelle-Bladou, Marc Bourlière, and Paul Castellani

Subjects
Hepatitis C virus, medicine.medical_treatment, Pharmacology, medicine.disease_cause, Antiviral Agents, chemistry.chemical_compound, Pegylated interferon, medicine, Potency, Humans, NS5A, NS5B, Protease, Hepatology, business.industry, Ribavirin, Gastroenterology, virus diseases, Hepatitis C, Chronic, Virology, Regimen, chemistry, Drug Therapy, Combination, business, medicine.drug, Forecasting
Abstract

The launch of first-generation protease inhibitors (PIs) was a major step forward in hepatitis C virus (HCV) treatment. However, this major advance has, up to now, only been applicable to genotype-1 patients. Second-wave and second-generation PIs appear to achieve higher antiviral potency, with pan-genotype activities, fewer side-effects and potential activity against PI-resistant mutation by second-generation PIs, through more convenient daily administration. Other direct-acting antivirals (DAAs) include NS5B inhibitors such as nucleoside/nucleotide inhibitors (NIs) and non-nucleoside inhibitors (NNIs). NIs have similar efficacy across all genotypes and present with the highest barrier to resistance of all DAAs to date. PSI-7977, a pyrimidine nucleotide analogue, also has highly potent antiviral activity across all HCV genotypes. In combination with ribavirin in an interferon-free regimen, it can achieve a 100% sustained viral response (SVR) rate in genotype 2/3 treatment-naive patients. In association with pegylated interferon and ribavirin (PR), it achieves an SVR of 91% in genotype-1 naive patients. NNIs in association with PR appear to be less potent, but they may nonetheless play a key role in many of the combination trials including either PIs or NIs. NS5A inhibitors also exhibit highly potent antiviral activity. Evaluation of their activity in combination with PIs demonstrated for the first time that an interferon-free regimen can cure genotype-1b null-responder patients. Furthermore, quadruple therapy with PR can achieve a 100% SVR in genotype-1 null-responder patients. Other players in the field, such as cyclophilin inhibitors and therapeutic vaccines, may have a role in combination with DAAs. The near future of HCV treatment looks promising. However, whether or not DAA combinations will lead to an interferon-free regimen for all patients remains an open question.

Published
2012

18. Future treatment of patients with HCV cirrhosis

Author

Xavier Adhoute, Valérie Oules, Isabelle Portal, Asma Khaloun, Souad Benali, Claire Wartelle-Bladou, Marc Bourlière, and Paul Castellani

Subjects
Liver Cirrhosis, medicine.medical_specialty, Cirrhosis, Serine Proteinase Inhibitors, Proline, Hepatitis C virus, medicine.disease_cause, Gastroenterology, Antiviral Agents, Telaprevir, Polyethylene Glycols, chemistry.chemical_compound, Fibrosis, Recurrence, Internal medicine, Boceprevir, Ribavirin, medicine, Humans, In patient, Hepatology, business.industry, Interferon-alpha, Hepatitis C, Chronic, Viral Load, medicine.disease, Recombinant Proteins, Regimen, chemistry, Drug Therapy, Combination, business, Oligopeptides, medicine.drug
Abstract

Of all hepatitis C virus (HCV) patients, those with cirrhosis are most in need of treatment because of increased morbidity and mortality. Treatment with pegylated-interferon (PEG-IFN) and ribavirin (RBV) (PR) has definitely shown the benefits of successful treatment by improving fibrosis, causing the regression of cirrhosis and reducing and preventing cirrhosis-related complications. However, the sustained virological response (SVR) is lower in patients with cirrhosis. First generation protease inhibitors (boceprevir and telaprevir) in combination with PR are a major advancement in the treatment of both naive and treatment-experienced genotype 1 patients. In naive patients, the SVR rate with the triple regimen with boceprevir was increased by 14% in patients with severe fibrosis or cirrhosis compared with PR. This benefit was lower than that observed in patients with mild or moderate fibrosis (30%). The SVR rate of the triple regimen with telaprevir was increased by 10–30% compared with PR in patients with severe fibrosis or cirrhosis compared with nearly 30% in patients with mild or moderate fibrosis. In treatment-experienced patients, previous relapsers have the highest increase in SVR with the triple regimen compared with PR, whatever the status of fibrosis. Previous partial or non-responder patients with cirrhosis had lower SVR rates than those without cirrhosis. However, the benefits of telaprevir and boceprevir vs PR was maintained. Previous non-responder patients with cirrhosis benefited the least from treatment. The relapse rate was always higher and side effects were more frequent in patients with cirrhosis compared with those without. First generation protease inhibitors plus PR appear to be a new step forward in the management of HCV genotype 1 patients with cirrhosis.

Published
2012

19. [Treatment of hepatitis C]

Author

Marc, Bourlière, Asma, Khaloun, Paul, Castellani, Isabelle, Portal, Christelle, Ansaldi, Xavier, Adhoute, and Stanislas, Pol

Subjects
Humans, Interferon-alpha, Interferon alpha-2, Antiviral Agents, Hepatitis C, Recombinant Proteins
Abstract

Hepatitis C treatment has made a lot of progress in the last two decades. Treatment with pegylated interferon and ribarin is associated with sustained virological response in more than 50% of patients. This improvement is due in one part to the adaptation of treatment dose and duration according to genotype, liver fibrosis and response-guided therapy, fibrosis in another part to a better pretreatment management of co-morbidities and a better prevention and management of side effects. New direct antiviral agents will become soon available and will lead to an improvement of sustained virological response with maybe more complex therapy leading to a new management of patients.

Published
2011

20. Optimized stepwise combination algorithms of non-invasive liver fibrosis scores including Hepascore in hepatitis C virus patients

Author

Marc Bourlière, Danielle Botta-Fridlund, C. Wartelle-Bladou, Denis Ouzan, M. A. Rosenthal-Allieri, Patrick Delasalle, Philippe Halfon, Paul Castellani, E. Rosenthal, Christophe Renou, Isabelle Portal, Guillaume Penaranda, Albert Tran, L. Lecomte, and Valérie Oules

Subjects
Liver Cirrhosis, Male, Hepatitis C virus, Biopsy, medicine.disease_cause, Cohort Studies, Predictive Value of Tests, Medicine, Humans, Pharmacology (medical), Hepatology, Receiver operating characteristic, medicine.diagnostic_test, business.industry, FibroTest, Gastroenterology, Hepatitis C, Hepatitis C, Chronic, Middle Aged, Viral Load, medicine.disease, Cross-Sectional Studies, Treatment Outcome, Liver, ROC Curve, Predictive value of tests, Liver biopsy, Disease Progression, Female, business, Algorithm, Viral load, Algorithms, Biomarkers
Abstract

Summary Background Non-invasive liver fibrosis scores such as Hepascore (HS) have been proposed as an alternative to liver biopsy in hepatitis C virus (HCV)-infected patients. Aim To validate HS as an alternative to liver biopsy and Fibrotest (FT) and propose five optimized combination algorithms to improve diagnostic accuracy. Methods The cohort included 467 patients with HCV. There were 274/467 (59%) men, and mean age was 47 ± 12 years. Results Hepascore area under ROC curves (AUC) for ≥F2, F3F4 and F4 diagnosis were 0.82, 0.84 and 0.90 respectively, in the same range as FT. HS and FT were concordant in 387/467 (82%) for fibrosis staging. Among these patients, 342/387 (88%) were concordant with liver biopsy. AUCs of aspartate aminotransferase (AST) to Platelets Ratio Index (APRI) and Forns for ≥F2 were 0.76 and 0.73 (0.65–0.79) respectively. The algorithm combining APRI and HS had the highest rate of avoided liver biopsies (45%) with a high diagnostic accuracy (91%). Conclusions Hepascore is an accurate non-invasive marker for ≥F2 and F4 diagnosis in HCV patients. In a pragmatic approach, a stepwise optimized algorithm combining APRI and FT or HS considerably increases diagnostic accuracy and avoided liver biopsies.

Published
2008

21. Accuracy of hyaluronic acid level for predicting liver fibrosis stages in patients with hepatitis C virus

Author

Philippe Halfon, Albert Tran, Christophe Renou, Danielle Botta-Fridlund, Isabelle Allemand, Alessandra Rosenthal-Allieri, Denis Ouzan, Marc Bourlière, R. Deydier, Guillaume Penaranda, and Isabelle Portal

Subjects
medicine.medical_specialty, Cirrhosis, Hepatology, medicine.diagnostic_test, business.industry, Research, Hepatitis C virus, Serum Hyaluronic Acid, medicine.disease, medicine.disease_cause, Gastroenterology, Liver disease, Fibrosis, Internal medicine, Liver biopsy, Biopsy, medicine, business
Abstract

Background In patients with chronic hepatitis C virus, liver biopsy is the gold standard for assessing liver disease stage; nevertheless, it is prone to complications, some of them serious. Non-invasive methods have been proposed as surrogate markers for liver fibrosis. It was shown that serum hyaluronic acid (HA) level increases with the development for liver fibrosis. The aim of this study was to evaluate the diagnostic value of HA as well as to determine the HA level cut-off for predicting the presence or absence of fibrosis, severe fibrosis, and cirrhosis. Results 405 patients with chronic hepatitis C were prospectively included with biomarker measurement and liver biopsy done the same day: 151 in the training set (only biopsy lengths of 25 mm or more) and 254 in the validation set. For the discrimination of significant fibrosis, severe fibrosis, and cirrhosis in the training set, the areas under curve (AUCs) were 0.75 ± 0.03, 0.82 ± 0.02, and 0.89 ± 0.03, respectively. Absence of significant fibrosis, severe fibrosis, and cirrhosis can be predicted by HA levels of 16, 25, and 50 μg/l, respectively (with negative predictive values of 82%, 89%, and 100%, in the same order). Presence of significant fibrosis, severe fibrosis, and cirrhosis can be predicted by HA levels of 121, 160, and 237 μg/l, respectively (with positive predictive values of 94%, 100%, and 57%, in the same order). Conclusion In the validation set, HA was accurate in predicting significant fibrosis, severe fibrosis, and cirrhosis with AUCs of 0.73, 0.77, and 0.97, respectively. Moreover, accurate HA level cut-offs were defined for predicting significant fibrosis, severe fibrosis, and cirrhosis. Thus, the study supports that HA level may be clinically useful as a non-invasive marker for liver fibrosis and/or cirrhosis.

Published
2005
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22. Changing of hepatitis C virus genotype patterns in France at the beginning of the third millenium: The GEMHEP GenoCII Study

Author

G. Thiefin, P. Chevallier, Ghassan Riachi, Françoise Stoll-Keller, V. Gerolami, B. Fouqueray, C. Silvain, Catherine Laffont, P. Couzigou, Christopher Payan, C. Chaput, Stanislas Pol, Armand Abergel, Michel Branger, Thomas Bourlet, Philippe Halfon, J.-J. Lefrère, Jacques Izopet, P. Sogni, Florence Grattard, Françoise Lunel-Fabiani, A. Charrois, M. Coudé, Michelle Martinot-Peignoux, Marc Bourlière, Pascale Trimoulet, Gilles Duverlie, Claudine Buffet-Janvresse, P. Opolon, M. Doffoel, Jean-Michel Pawlotsky, Marie-Laure Chaix, Jean-Didier Grangé, Marc Bogard, Christian Trepo, E. Plouvier, K. Barange, V. Brodard, Arielle R. Rosenberg, D. Cointe, Sophie Alain, N. Bled, Patrick Marcellin, V. Thibault, Isabelle Portal, Cécile Henquell, Lawrence Serfaty, Véronique Loustaud-Ratti, Françoise Roudot-Thoraval, G. Agius, A. Blanchi, Isabelle Fouchard-Hubert, Christophe Hézode, 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), Service d'hépatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, CHU Clermont-Ferrand, Service d'hépato-gastro-entérologie [APHP Henri Mondor], Biologie moléculaire et cellulaire des microorganismes (EA3175), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Limoges (UNILIM), Service de Bactériologie, Virologie, Hygiène [CHU Limoges], CHU Limoges, Laboratoire alphabio, Service d'Hépato-gastroentérologie, Assistance Publique - Hôpitaux de Marseille (APHM), Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépato-gastroentérologie, CHU Strasbourg-Hopital Civil, Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Necker - Enfants Malades [AP-HP], Service d'hépatologie [Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'hépatologie [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Saint-Antoine [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Biologie moléculaire et cellulaire des microorganismes ( EA3175 ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Limoges ( UNILIM ), Assistance Publique - Hôpitaux de Marseille ( APHM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], and Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP]

Subjects
Male, Cirrhosis, MESH : Genotype, Hepacivirus, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, medicine.disease_cause, Polymerase Chain Reaction, MESH : Hepacivirus, MESH: Genotype, Cohort Studies, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Genotype, Epidemiology, MESH : Female, MESH: Hepacivirus, MESH : Polymerase Chain Reaction, MESH: Cohort Studies, 0303 health sciences, education.field_of_study, Molecular Epidemiology, MESH: Middle Aged, MESH : Adult, Middle Aged, Hepatitis C, 3. Good health, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious Diseases, MESH: RNA, Viral, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Coinfection, RNA, Viral, 030211 gastroenterology & hepatology, Female, France, Adult, medicine.medical_specialty, MESH : Male, Hepatitis C virus, Population, MESH : Cohort Studies, Biology, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH : Epidemiology, Molecular, 03 medical and health sciences, MESH: Epidemiology, Molecular, Virology, medicine, MESH : RNA, Viral, Humans, MESH : Middle Aged, Risk factor, MESH : France, education, 030304 developmental biology, Hepatitis B virus, MESH: Hepatitis C, MESH: Humans, Hepatology, MESH : Humans, MESH: Adult, MESH: Polymerase Chain Reaction, MESH : Hepatitis C, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, MESH: France, MESH: Female
Abstract

International audience; This cross-sectional study aimed to investigate, during a short period between 2000 and 2001, in a large population of patients with chronic hepatitis C, the epidemiological characteristics of hepatitis C virus (HCV) genotypes in France. Data from 26 referral centres, corresponding to 1769 patients with chronic hepatitis C were collected consecutively during a 6-month period. HCV genotyping in the 5'-non-coding region (NCR) was performed in each center using the line probe assay (LiPA, in 63% of cases), sequencing (25%) or primer-specific polymerase chain reaction (PCR) (12%). HCV genotypes 1a, 1b, 2, 3, 4, 5, non-subtyped 1 and mixed infection were found in 18, 27, 9, 21, 9, 3, 11 and 1% of our population, respectively. HCV genotype distribution was associated with gender, age, source and duration of infection, alanine aminotransferase (ALT) levels, cirrhosis, alcohol consumption, hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection. In multivariate analysis, only the source of infection was the independent factor significantly associated with genotype (P = 0.0001). In conclusion, this study shows a changing pattern of HCV genotypes in France, with i.v. drug abuse as the major risk factor, an increase of genotype 4, and to a lesser extent 1a and 5, and a decrease of genotypes 1b and 2. The modification of the HCV genotype pattern in France in the next 10 years may require new therapeutic strategies, and further survey studies.

Published
2005
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23. Retreatment with interferon and ribavirin vs interferon alone according to viraemia in interferon responder-relapser hepatitis C patients: a prospective multicentre randomized controlled study

Author

Gérard Thiéfin, C. Mathieu‐Chandelier, J. Gouvernet, P. Couzigou, A. P. Gauthier, J. M. Debonne, Pierre-Henri Bernard, V. Gerolami, M. Picon, F.X. Caroli-Bosc, Isabelle Portal, A. Gérolami, I. Alleman, H. Khiri, C. Zamora, V. de Ledinghen, Philippe Sogni, J. C. Grimaud, C. Eugène, F. Blanc, François Bailly, Stanislas Pol, Denis Ouzan, G. Botti, Armando Abergel, Philippe Halfon, D. Vetter, Olivier Chazouillères, Danielle Botta-Fridlund, F. Doll, J. P. Arpurt, S. Ducloux, X. Moreau, M. Bourlière, and Dominique Larrey

Subjects
Adult, Male, medicine.medical_specialty, Combination therapy, Hepacivirus, Interferon alpha-2, Gastroenterology, Antiviral Agents, law.invention, chemistry.chemical_compound, Randomized controlled trial, law, Interferon, Recurrence, Virology, Internal medicine, Ribavirin, medicine, Humans, In patient, Prospective Studies, Viremia, Hepatology, business.industry, Interferon-alpha, Hepatitis C, Hepatitis C, Chronic, Middle Aged, Viral Load, medicine.disease, Recombinant Proteins, Infectious Diseases, Treatment Outcome, chemistry, Sustained response, Retreatment, RNA, Viral, Drug Therapy, Combination, Female, business, Viral load, medicine.drug
Abstract

Low pretreatment viral load has consistently been shown to be an independent predictor of sustained response (SR) in patients with chronic hepatitis C infection. We assessed the efficacy of interferon (IFN) plus ribavirin vs IFN alone in low viraemic patients (2 millions copies/mL) who had relapsed to a previous course of IFN and the efficacy of 24 vs 48 week combination therapy in high viraemic patients. Two hundred and ninety-seven patients were randomly assigned to one of the four regimens after stratification on pretreatment viral load. All patients received IFN-alpha2b (6 million units thrice weekly for 24 weeks and 3 million units thrice weekly for 24 weeks). Patients with low viraemia received either IFN-alpha2b alone for 48 weeks (R1: 42 patients) or IFN-alpha2b plus ribavirin (600 mg/day) for 24 weeks and IFN-alpha2b alone for the next 24 weeks (R2: 48 patients). Patients with high viral load received either IFN-alpha2b plus ribavirin for 24 weeks and then IFN-alpha2b alone for the next 24 weeks (R3: 104 patients) or IFN-alpha2b plus ribavirin for 48 weeks (R4: 103 patients). In low viraemic patients the rate of SR was 37.7% in group R1 and 59.6% in group R2 (P0.05). In high viraemic patients, the rate of SR was 44.7% in group R3 and 51.4% in group R4 (P: NS). Thirty-one patients discontinued treatment (10.4%) without difference regarding treatment regimen. In the regimen using ribavirin we found no difference in terms of SR between patients receiving a dose of ribavirin below 10.6 mg/kg/day (55%) or over 10.6 mg/kg/day (58%). Histological improvement occurred in 70.2% of patients regardless of the regimen. Logistic regression showed that genotype 2 and 3, Knodell score6 and alanine aminotransferase pretreatment level3 x upper limit of normal were significantly and independently correlated with SR. In low viraemic patients who relapsed to a previous IFN treatment, combination therapy using high-dose IFN and low-dose ribavirin is better than high-dose IFN alone. In high viraemic patients there was no benefit in increasing the duration of combination therapy from 24 to 48 weeks. In this study, it was found that low dose of ribavirin can be used safely and there is no effect of ribavirin dose on SR.

Published
2003

24. [Treatment of chronic hepatitis C in special groups]

Author

Marc, Bourlière, Philippe, Halfon, and Isabelle, Portal

Subjects
Adult, Time Factors, Mental Disorders, Interferon-alpha, Hepatitis C, Chronic, Hemophilia A, Antiviral Agents, Kidney Transplantation, Liver Transplantation, Renal Dialysis, Acute Disease, Ribavirin, Humans, Thalassemia, Drug Therapy, Combination, Child, Bone Marrow Transplantation, Follow-Up Studies
Published
2002

25. [Factors related to screening of hepatitis C virus in general medicine]

Author

Michel, Rotily, Sandrine, Loubière, Johanne, Prudhomme, Isabelle, Portal, Albert, Tran, Philippe, Hofliger, Dominique, Valla, and Jean-Paul, Moatti

Subjects
Adult, Male, Risk Factors, Humans, Physicians, Family, Female, France, Practice Patterns, Physicians', Family Practice, Substance Abuse, Intravenous, Hepatitis C
Abstract

Despite the high prevalence of hepatitis C in France ( approximately 1.2%), a large proportion of people infected with hepatitis C virus (HCV) are not known aware of their status. The objective of this study was to investigate the factors related to screening in general medicine.Three hundred and one general practitioners were interviewed by phone in South-Eastern France about their HCV screening practices, knowledge of the epidemic, of the natural course of the disease, and opinions about health care for people infected with HCV.While general practitioners often offered HCV screening to intravenous drug users, screening for people who had received blood transfusion, and identification of risk factors among patients were not satisfactory. Multivariate analysis showed that certain characteristics in general practitioners were negatively and independently related to the frequency of HCV screening, especially: general practitioners older than 40 (odds-ratio: 3.12), general practitioners who did not care for intravenous drug users (odds-ratio: 2.24) and did not prescribe human immunodeficiency virus tests (odds-ratio: 5.55). Other characteristics such as awareness of the course of hepatitis C and health care were also associated with HCV screening. Conversely knowledge of the size of the epidemic was not related to better HCV screening practices.Our study shows that knowledge about the size of the epidemic and the natural history of hepatitis C, HCV screening practices and investigation of risk factors among patients are not satisfactory among South-eastern French general practitioners. Although HCV screening and health care must be improved among intravenous drug users, hepatitis C should not be considered as a disease of injecting drug users only by general practitioners and the population. Efforts should be made so that hepatitis C is recognized as a global public health issue, and training of general practitioners should be improved to investigate risk factors and offer HCV screening instead of merely dramatizing the situation.

Published
2002

26. Epidemiological changes in hepatitis C virus genotypes in France: evidence in intravenous drug users

Author

C. Boustiere, L. Lecomte, Isabelle Portal, G. Lambot, R. Daniel, M. Bourlière, Hervé Perrier, R. Loyer, M. Jullien, O. Lebars, J. M. Barberin, Philippe Halfon, Hacène Khiri, S. Benali, V. Guagliardo, and Michel Rotily

Subjects
Adult, medicine.medical_specialty, Time Factors, Genotype, Hepatitis C virus, Population, Hepacivirus, Logistic regression, medicine.disease_cause, Gastroenterology, Virology, Internal medicine, Epidemiology, medicine, Prevalence, Distribution (pharmacology), Humans, education, Substance Abuse, Intravenous, education.field_of_study, Hepatology, Intravenous drug, business.industry, Odds ratio, Hepatitis C, Chronic, Infectious Diseases, France, business
Abstract

Hepatitis C virus (HCV) genotypes are distributed differently depending on geography and route of infection. We characterized the distribution of genotypes in a large cohort of patients with chronic hepatitis C in the South-east of France and evaluated the relative prevalence according to time of acquisition. One thousand, one hundred-and-eighty-three patients who were anti-HCV-positive were studied. HCV genotype distribution has changed significantly from the 1960s to 2000. The prevalence of genotype 1b decreased from 47% before 1978 to 18.8% in the 1990s while the prevalence of genotype 1a and 3a increased during the same period from 18% and 15.3% to 28.8% and 26.3%, respectively. The logistic regression model showed that genotype 1a was significantly more common in patients infected through intravenous drug injection odds ratio ((OR): 2.08, P < 0.01) and after 1990 (OR: 1.98, P < 0.05). Genotype 1b was significantly less frequent in patients infected through intravenous drug injection (OR: 0.17, P < 0.001) and has decreased since 1978 (OR: 0.27, P < 0.001). Genotype 3a was independently associated with intravenous drug injection (OR: 6.1, P < 0.001) and tattooing (OR: 8.01, P < 0.001) and was more frequent in the 1979-90 period (OR: 2.05 and 1.74, P < 0.001 and P < 0.05). Our results show a modification of HCV genotypes distribution over the last four decades due to an increase of intravenous drug use (IVDU) contamination and an evolution of HCV genotypes distribution only in IVDU population characterized by a decrease of genotype 1b, an increase of genotype 3a from 1970 to 1990 and a higher increase of genotype 1a which is currently the predominant genotype in our population.

Published
2002

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

Author

Thierry Poynard, Veronique Loustaud Ratti, Dominique Larrey, Isabelle Portal, Patrick Marcellin, Albert Tran, Vincent Di Martino, Patrick Hillon, Jean-Pierre Bronowicki, Isabelle Rosa, Damien Lucidarme, Marc Bourlière, Ghassan Riachi, Christophe Hézode, Pierre Attali, Yoann Barthe, Patrice Cacoub, Olivier Chazouillères, Pierre Bernard, Veronique Grando–Lemaire, Jérôme Gournay, Sophie Metivier, Thong Dao, Stanislas Pol, Jean-Pierre Zarski, Valérie Canva, Victor de Lédinghen, Ventzislava Petrov–Sanchez, Jean-Michel Pawlotsky, Armand Abergel, Laurent Alric, Didier Samuel, Fabrice Carrat, Hélène Fontaine, Jean Jacques Raabe, Céline Dorival, Fabien Zoulim, Xavier Causse, Dominique Guyader, T. Fontanges, Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service d'hépatologie médicale [CHU Cochin], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Epidémiologie, Systèmes d'Information, Modélisation, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP], Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Services d'hépatologie, Hospices Civils de Lyon ( HCL ), Service d'hépatologie, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -CHU Saint-Eloi, Cellules souches normales et cancéreuses, Université Montpellier 1 ( UM1 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Service d'hépato-gastro-entérologie, Hôpital Huriez-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Pathogénèse et traitement de l'hépatite fulminante et du cancer du foie, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance Publique - Hôpitaux de Marseille ( APHM ), Service de médecine interne et maladies digestives, CHU Toulouse [Toulouse], Pharmacochimie et Pharmacologie Pour le Développement ( PHARMA-DEV ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique ( CNRS ), Service d'Hépato-gastro-entérologie [CHR Metz-Thionville], Centre hospitalier régional Metz-Thionville ( CHR Metz-Thionville ), Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département d'hépato-gastroentérologie, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Centre de recherche biomédicale Bichat-Beaujon ( CRB3 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Hépato-Gastroentérologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques ( RESINFIT ), CHU Limoges-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST ), Université de Limoges ( UNILIM ) -Université de Limoges ( UNILIM ), Service d'hépatologie [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], CHU Etaing, Image Science for Interventional Techniques ( ISIT ), Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Clermont Université-Centre National de la Recherche Scientifique ( CNRS ), Service des maladies du foie, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [Rennes], Foie, métabolismes et cancer, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Gastro-entérologie - Hépatologie [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Département digestif, CHU Nice, Centre méditérannéen de médecine moléculaire ( C3M ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Hépato-gastro-entérologie et oncologie digestive, Centre Hospitalier Régional d'Orléans ( CHR ), Service d'Hépato-Gastro-Enterologie et Nutrition [Caen], Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -CHU Caen, Mobilités : Attention, Orientation et Chronobiologie ( COMETE ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Groupe Hospitalier de l'Institut Catholique Lillois, Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Service de médecine interne [CHU Pitié-Salpétrière], Immunologie - Immunopathologie - Immunothérapeutique ( I3 ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Hôpital Hôtel-Dieu [Paris], Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Jean Verdier, Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, CH Pierre Oudot Bourgoin-Jallieu, CHI Créteil, Recherches fondamentales, cliniques et thérapeutiques sur les hépatites virales, ANRS, Centre National de Référence Virus des hépatites B, C et Delta, Pôle de Pharmacie - Santé Publique - Information médicale [Saint-Antoine], Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), This study was sponsored and funded by The National Agency for Research on AIDS and Viral Hepatitis (ANRS).The ANRS C020 CUPIC cohort study was conducted with the support and participation of the Association Française pour l'Etude du Foie (AFEF), and CUPIC STUDY GROUP

Subjects
Liver Cirrhosis, Male, Cirrhosis, Comorbidity, Hepacivirus, medicine.disease_cause, Gastroenterology, Polyethylene Glycols, Telaprevir, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Pegylated interferon, boceprevir, Prospective Studies, Treatment Failure, Aged, 80 and over, Middle Aged, Recombinant Proteins, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, Oligopeptides, medicine.drug, Adult, medicine.medical_specialty, Genotype, Proline, Hepatitis C virus, Antiviral Agents, 03 medical and health sciences, Boceprevir, Internal medicine, Ribavirin, medicine, chronic hepatitis C, Humans, telaprevir, Adverse effect, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Aged, Hepatology, business.industry, cirrhosis, Interferon-alpha, Odds ratio, Hepatitis C, Chronic, medicine.disease, chemistry, Multivariate Analysis, Immunology, business, Follow-Up Studies
Abstract

International audience; BACKGROUND & AIMS: We investigated the effectiveness of the protease inhibitors peginterferon and ribavirin in treatment-experienced patients with hepatitis C virus (HCV) genotype 1 infection and cirrhosis. METHODS: In the Compassionate Use of Protease Inhibitors in Viral C Cirrhosis study, 511 patients with HCV genotype 1 infection and compensated cirrhosis who did not respond to a prior course of peginterferon and ribavirin (44.3% relapsers or patients with viral breakthrough, 44.8% partial responders, and 8.0% null responders) were given either telaprevir (n = 299) or boceprevir (n = 212) for 48 weeks. We assessed percentages of patients with sustained viral responses 12 weeks after therapy and safety. This observational study did not allow for direct comparison of the 2 regimens. RESULTS: Among patients given telaprevir, 74.2% of relapsers, 40.0% of partial responders, and 19.4% of null responders achieved SVR12. Among those given boceprevir, 53.9% of relapsers, 38.3% of partial responders, and none of the null responders achieved SVR12. In multivariate analysis, factors associated with SVR12 included prior response to treatment response, no lead-in phase, HCV subtype 1b (vs 1a), and baseline platelet count greater than 100,000/mm(3). Severe adverse events occurred in 49.9% of cases, including liver decompensation, severe infections in 10.4%, and death in 2.2%. In multivariate analysis, baseline serum albumin level less than 35 g/L and baseline platelet counts of 100,000/mm(3) or less predicted severe side effects or death. CONCLUSIONS: Relatively high percentages of real-life, treatment-experienced patients with HCV genotype 1 infection and cirrhosis respond to the combination of peginterferon and ribavirin with telaprevir or boceprevir. However, side effects are frequent and often severe. Baseline levels of albumin and platelet counts can be used to guide treatment decisions. ClinicalTrials.gov number: NCT01514890.

Published
2014
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28. Covert transmission of hepatitis C virus during bloody fisticuffs

Author

Philippe Halfon, Gérard Lambot, H. Khiri, Cecile Mengotti, Pierre David, Souad Benali, Christian Boustière, Hervé Perrier, Isabelle Portal, Monique Jullien, Yves Quentin, and Marc Bourlière

Subjects
Male, Genotype, Hepatitis C virus, Football, Poison control, Violence, medicine.disease_cause, chemistry.chemical_compound, medicine, Humans, NS5B, Hepatology, business.industry, Transmission (medicine), Gastroenterology, virus diseases, Hepatitis C, Boxing, Hepatitis C, Chronic, Middle Aged, medicine.disease, Virology, digestive system diseases, Bloody, chemistry, DNA, Viral, Viral disease, business
Abstract

Hepatitis C virus (HCV) is transmitted primarily through direct percutaneous exposure to infected blood. Sporadic HCV cases exist and may represent more than 10% of HCV transmission. We report the first case of documented transmission of HCV during a fight from a person who unknowingly had chronic HCV infection to a person who subsequently contracted acute hepatitis C. Patient-to-patient transmission was ascertained by sequence analysis of part of the NS5B genome and phylogenetic analysis. This case report suggests that sporadic HCV infection may be a result of blood exposure. This example of transmission could have a major impact in sports such as boxing or rugby. We suggest that in any fight, single use or nondisposable material should be used to dry blood to avoid such contamination.

Published
2000

29. Assessment of Spontaneous Fluctuations of Viral Load in Untreated Patients with Chronic Hepatitis C by Two Standardized Quantitation Methods: Branched DNA and Amplicor Monitor

Author

Marc Bourlière, Isabelle Portal, G. Cartouzou, A. P. Gauthier, Philippe Halfon, G Halimi, Jean Marc Feryn, Monique Jullien, Patrice Bertezene, Danielle Botta-Fridlund, V. Gerolami, and Hacène Khiri

Subjects
Microbiology (medical), Adult, Male, Hepatitis C virus, Hepacivirus, Viremia, medicine.disease_cause, Polymerase Chain Reaction, Virus, Flaviviridae, Virology, medicine, Humans, Prospective Studies, biology, virus diseases, Hepatitis C, Chronic, Middle Aged, Viral Load, medicine.disease, Branched DNA assay, biology.organism_classification, RNA, Viral, Female, Viral disease, Viral load
Abstract

Quantitation of hepatitis C virus (HCV) RNA in serum has been used to predict and monitor the efficacy of interferon therapy in chronic HCV infection. We prospectively studied the fluctuation of viremia by a longitudinal follow-up of HCV RNA levels for 2 months in six untreated patients. Spontaneous fluctuations of HCV RNA ranged from 2.8- to 5.7-fold with branched DNA assay and from 2.9- to 5.6-fold with Monitor. These large spontaneous fluctuations (up to 0.75 log), observed daily, weekly, and monthly, raise doubt about the clinical value of a single assessment of pretherapeutic viremia.

Published
1998

30. 1167 IL-28 GENE VARIATION PREDICTS WHO WILL RESPOND TO INTERFERON-BASED TREATMENT OF CHRONIC HEPATITIS C IN A FRENCH COHORT

Author

M. Bourlière, Albert Tran, Paul Castellani, Alain Dessein, Claire Wartelle, Denis Ouzan, Christophe Renou, Danielle Botta, Philippe Halfon, Laurent Argiro, Guillaume Penaranda, Valérie Oules, and Isabelle Portal

Subjects
Pathology, medicine.medical_specialty, Variation (linguistics), Hepatology, Chronic hepatitis, Interferon, business.industry, Cohort, Immunology, medicine, business, Gene, medicine.drug
Published
2010
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31. CA 23-Combinaison de marqueurs non-invasifs (fibrotest, hepascore, APRI, et forns) en alternative à la biopsie hépatique, pour le diagnostic de fibrose du foie chez des malades infectés par le VHC

Author

Christophe Renou, Guillaume Penaranda, Claire Wartelle, Paul Castellani, D. Botta-Fridlund, Denis Ouzan, Patrick Delasalle, René Gerolami, Isabelle Portal, Philippe Halfon, M. Bourlière, Albert Tran, L. Lecomte, and Eric Rosenthal

Subjects
Gynecology, medicine.medical_specialty, business.industry, Gastroenterology, Medicine, General Medicine, business
Published
2006
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32. P.363 Validation of hepascore for diagnosis of liver fibrosis in HCV patients and determination of a new algorithm

Author

Guillaume Penaranda, Claire Wartelle, Paul Castellani, Denis Ouzan, Philippe Halfon, D. Botta-Fridlund, Eric Rosenthal, M. A. Rosenthal-Allieri, René Gerolami, Christophe Renou, Isabelle Portal, Marc Bourlière, Albert Tran, L. Lecomte, and P. Delasalle

Subjects
medicine.medical_specialty, Infectious Diseases, business.industry, Virology, Liver fibrosis, Internal medicine, Medicine, business, Gastroenterology
Published
2006
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33. C028 - Est-ce que l’amantadine améliore la réponse virologique long terme de l’association Peg-Interféron-alpha2b/ribavirine chez les malades atteints d’hépatite chronique C n’ayant jamais reçu de traitement ? Étude prospective randomisée multicentrique en double aveugle : résultats préliminaires chez 200 malades

Author

E. Verdier, Odile Goria, Dominique Larrey, P. Chassagne, V. Calay, Albert Tran, Jean-Pierre Daurès, Georges-Philippe Pageaux, Isabelle Portal, S. Hachemane, Jean-Pierre Arpurt, Philippe Mathurin, M. Bourlière, and C. Bozonnat

Subjects
Gynecology, medicine.medical_specialty, business.industry, Gastroenterology, medicine, General Medicine, business
Published
2005
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34. CA5 - Valeurs prédictives de l’acide hyaluronique pour la fibrose et la cirrhose chez des malades atteints par le virus de l’hépatite C chronique : comparaison au fibrotest, taux de prothrombine et numération des plaquettes

Author

Philippe Halfon, Jean-Jacques Bertrand, R. Deydier, C. Sattonet, I. Allemand, Michel Rotily, D. Botta-Fridlund, H.P. Bonnot, Isabelle Portal, Claude Degott, T. Benderitter, M.F. Masseyeff, Denis Ouzan, Maria Alessandra Rosenthal-Allieri, Christophe Renou, Guillaume Penaranda, Albert Tran, Marie-Christine Saint-Paul, and M. Bourlière

Subjects
business.industry, Gastroenterology, Medicine, General Medicine, business, Molecular biology
Published
2004
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35. CO31 - Validation indépendante d’index non-invasifs pour la prédiction de fibrose et de cirrhose chez des malades atteints d’hépatite C chronique : comparaison entre les scores fibrotest, apri et forns

Author

Philippe Halfon, Marie-Christine Saint-Paul, M. Bourlière, C. Sattonet, I. Allemand, Guillaume Penaranda, D. Botta-Fridlund, H.P. Bonnot, Isabelle Portal, Albert Tran, Maria Alessandra Rosenthal-Allieri, Jean-Jacques Bertrand, R. Deydier, Christophe Renou, Michel Rotily, Denis Ouzan, T. Benderitter, Claude Degott, and M.F. Masseyeff

Subjects
Gynecology, medicine.medical_specialty, business.industry, Gastroenterology, medicine, General Medicine, business
Published
2004
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36. 319 Treatment with pegylated-interferon alfa 2B in relapsers to standard interferon + ribavirin in chronic hepatitis C: Efficacy and safety results from a randomized multicentric French study

Author

Valérie Canva, Philippe Halfon, Danielle Botta-Fridlund, Marc Bouliere, Michel Rotily, Karl Barange, Isabelle Portal, Patrice Couzigou, and Dominique Larrey

Subjects
medicine.medical_specialty, Hepatology, business.industry, Ribavirin, Gastroenterology, Pegylated interferon alfa-2b, chemistry.chemical_compound, chemistry, Chronic hepatitis, Interferon, Internal medicine, medicine, business, medicine.drug
Published
2003
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37. 68 Independent prospective multicenter validation of biochemical markers (fibrotest-actitest) for the prediction of liver fibrosis and activity in patients with chronic hepatitis C

Author

Philippe Halfon, Isabelle Portal, Michel Rotily, A Rosenthal, Christophe Renou, Jean-Jacques Bertrand, A Sattonet, R. Deydier, Albert Tran, and M. Bourlière

Subjects
medicine.medical_specialty, Pathology, Hepatology, Chronic hepatitis, FibroTest, business.industry, Internal medicine, Liver fibrosis, Medicine, In patient, business, Gastroenterology, Biochemical markers
Published
2003
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38. The changing relative prevalence of HCV genotypes is due to modification of route of contamination and evolution of genotypes distribution in intravenous drug users

Author

S. Benali, Hervé Perrier, G. Lambot, Philippe Halfon, M. Bourlière, Isabelle Portal, M. Jullien, H. Khiri, C. Boustiere, and J. M. Barberin

Subjects
Veterinary medicine, Hepatology, Intravenous drug, business.industry, Genotype, HCV genotypes, Distribution (pharmacology), Contamination, Biology, business, Biotechnology
Published
2000
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39. Retreatment with interferon-riravirine according to viremia of interferon responder-relapser patients: French multicenter randomized controlled study

Author

V. de Ledinghen, Paul Castellani, H. Khiri, A. Gérolami, Danielle Botta-Fridlund, P. Couzigou, Pierre-Henri Bernard, Isabelle Portal, A. P. Gauthier, G. Botti, V. Gerolami, M. Bourlière, and Philippe Halfon

Subjects
medicine.medical_specialty, Hepatology, business.industry, Viremia, medicine.disease, Gastroenterology, law.invention, Randomized controlled trial, Interferon, law, Internal medicine, medicine, business, medicine.drug
Published
2000
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40. Liver failure due to recombinant alpha interferon

Author

Gilles Kaplanski, Yvon Berland, Isabelle Portal, Jean Marc Durand, Claudie Scheiner, and Jacques Soubeyrand

Subjects
business.industry, Liver failure, Insuficiencia hepatica, Alpha interferon, General Medicine, Virology, law.invention, law, Toxicity, Immunology, Recombinant DNA, Medicine, business, Interferon alfa, medicine.drug
Published
1991
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44. Liver fibrosis and all‐cause mortality in chronic HCV‐infected diabetic patients: A paradoxical association? (ANRS CO22 HEPATHER)

Author

Tangui, Barré, Clémence, Ramier, Vincent, Di Beo, Fabrice, Carrat, Hélène, Fontaine, Fabienne, Marcellin, Patrizia, Carrieri, Stanislas, Pol, Camelia, Protopopescu, Marie-Josée, Lafrance, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunité Innée - Innate Immunity, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), ANRS/AFEF Hepather study group: Delphine Bonnet, Virginie Sicart, François Bailly, Marjolaine Beaudoin, Dominique Giboz, Kerstin Hartig-Lavie, Marianne Maynard, Morane Cavellec, Marjorie Cheraud-Carpentier, François Raffi, Florian Vivrel, Jaouad Benhida, Jérôme Boursier, Paul Calès, Françoise Lunel, Frédéric Oberti, Nathalie Boyer, Audrey Gilibert, Nathalie Giuily, Giovanna Scoazec, Sandrine Fernandes, Sylvie Keser, Philippe Sultanik, Anaïs Vallet-Pichard, Juliette Foucher, Jean-Baptiste Hiriart, Aurore Mathias, Julien Vergniol, Chrystelle Ansaldi, 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, Nathalie Ganne-Carrié, Véronique Grando-Lemaire, Pierre Nahon, Alan Peltier, Judith Ung, Mariette Gougeon, Anne Guillygomarch, Caroline Jezequel, Romain Moirand, Thomas F Baumert, Michel Dofföel, Catherine Mutter, Pauline Simo-Noumbissie, Hélène Barraud, Mouni Bensenane, Abdelbasset Nani, Sarah Hassani-Nani, Marie-Albertine Bernard, Michael Bismuth, Ludovic Caillo, Stéphanie Faure, Georges-Philippe Pageaux, Marie P Ripault, Karl Barange, Christophe Bureau, Jean M Peron, Marie A Robic, Léa Tarallo, Marine Faure, Bruno Froissart, Marie-Noelle Hilleret, Vincent Leroy, 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 D Vallée, Mariagrazia Tateo, Armand Abergel, 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, Florent Artu, Valérie Canva, Sébastien Dharancy, Alexandre Louvet, Marc Bardou, Donya Da Costa Souhiel, Patrick Hillon, Marianne Latournerie, Yannick Bacq, Didier Barbereau, Charlotte Nicolas, Nisserine B Amara, Danièle Botta-Fridlund, Isabelle Portal, Moana Gelu-Simeon, Marie-Josée Lafrance, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), The cohort received financial support from the INSERM-ANRS (France Recherche Nord and Sud Sida-HIV Hépatites), the French ANR (Agence Nationale de la Recherche), the French DGS (Direction Générale de la Santé), Merck Sharp and Dohme, Janssen-Cilag, Gilead, Abbvie, Bristol-Myers Squibb and Roche. FC reports grants from INSERM-ANRS, during the conduct of the study, and personal fees from Imaxio, outside the submitted work. MB reports grants and personal fees from AbbVie and Gilead, outside the submitted work, and personal fees from MSD, Janssen, Boehringher Ingelheim, Intercept and Bristol-Myers Squibb, outside the submitted work. SP has received consulting and lecturing fees from Bristol-Myers Squibb, Janssen, Gilead, Roche, MSD, MYR-Pharma, Shionogi, Biotest and Abbvie, as well as grants from Bristol-Myers Squibb, Gilead, Roche and MSD. HF reports personal fees and invitations for medical meetings from Gilead, AbbVie, Bristol-Myers Squibb, MSD and Janssen, outside the submitted work. Other authors declare no financial support., and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Liver Cirrhosis, 0303 health sciences, medicine.medical_specialty, Hepatology, business.industry, Liver fibrosis, [SDV]Life Sciences [q-bio], Hepatitis C, Chronic, Antiviral Agents, Gastroenterology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Text mining, Internal medicine, Diabetes Mellitus, medicine, Humans, 030211 gastroenterology & hepatology, business, All cause mortality, ComputingMilieux_MISCELLANEOUS, Follow-Up Studies, 030304 developmental biology
Abstract

International audience; No abstract available

Published
2021
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45. Effectiveness of direct‐acting antivirals for chronic hepatitis C treatment in migrant and non‐migrant populations in France

Author

Mélanie Simony, Stanislas Pol, Elisabeth Delarocque-Astagneau, Hélène Fontaine, Fabrice Carrat, Tchadine Djaogol, Maël Baudoin, Fabienne Marcellin, Patrizia Carrieri, Ventzislava Petrov-Sanchez, Marc Bourlière, Camelia Protopopescu, Céline Dorival, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Recherches fondamentales, cliniques et thérapeutiques sur les hépatites virales [Paris] (ANRS), ANRS France Recherche Nord & sud Sida-hiv hépatites, Hôpital Saint-Joseph [Marseille], Biostatistique, Biomathématique, Pharmacoépidémiologie et Maladies Infectieuses (B2PHI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris]-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), The cohort received financial support from INSERM-ANRS (France Recherche Nord & Sud Sida-HIV Hépatites), the French ANR (Agence Nationale de la Recherche), the French DGS (Direction Générale de la Santé), Merck Sharp and Dohme, Janssen-Cilag, Gilead, Abbvie, Bristol-Myers Squibb and Roche., ANRS CO22 Hepather study group, ANRS-AFEF HEPATHER STUDY GROUP: Delphine Bonnet, Virginie Sicart (CHU Purpan, Toulouse, France), François Bailly, Marjolaine Beaudoin, Dominique Giboz, Kerstin Hartig-Lavie, Marianne Maynard(Hospices Civils de Lyon, Lyon, France), Morane Cavellec, Marjorie Cheraud-Carpentier, François Raffi, Florian Vivrel (Hôpital Hôtel-Dieu, Nantes, France), Jaouad Benhida, Jérôme Boursier, Paul Calès, Françoise Lunel, Frédéric Oberti (CHU Angers, Angers, France), Nathalie Boyer, Audrey Gilibert, Nathalie Giuily (Hôpital Beaujon, Clichy, France), Giovanna Scoazec (Hôpital Beaujon, Clichy, France and Hôpital Henri Mondor, Créteil, France), Sandrine Fernandes, Sylvie Keser, Philippe Sultanik, Anaïs Vallet-Pichard (Hôpital Cochin, Paris, France), Juliette Foucher, Jean-Baptiste Hiriart, Aurore Mathias, Julien Vergniol (Hôpital Haut-Lévêque, Pessac, Bordeaux, France), Chrystelle Ansaldi, Laëtitia Chouquet, Emilie De Luca, Valérie Oules (Hôpital Saint Joseph, Marseille, France), Rodolphe Anty, Eve Gelsi, Régine Truchi (CHU de Nice, Nice, France), Elena Luckina, Nadia Messaoudi, Joseph Moussali, (Groupe Hospitalier Pitié-Salpétrière, Paris, France), Barbara De Dieuleveult, Damien Labarriere, Pascal Poter, Si Nafa Si Ahmed (CHR La Source, Orléans, France), Nathalie Ganne-Carrié, Véronique Grando-Lemaire, Pierre Nahon, Alan Peltier, Judith Ung (Hôpital Jean Verdier, Bondy, France), Mariette Gougeon, Anne Guillygomarch, Caroline Jezequel (CHU Rennes, Rennes, France), Romain Moirand, Thomas F. Baumert, Michel Dofföel, Catherine Mutter, Pauline Simo-Noumbissie (Hôpitaux Universitaires de Strasbourg, Strasbourg, France), Hélène Barraud, Mouni Bensenane, Abdelbasset Nani, Sarah Hassani-Nani (CHU de Nancy, Vandoeuvre-lès-Nancy, France), Marie-Albertine Bernard (CHU de Nancy, Vandoeuvre-lès-Nancy, France and Centre Hospitalier Régional, Metz, France), Michael Bismuth, Ludovic Caillo, Stéphanie Faure, Georges-Philippe Pageaux, Marie Pierre Ripault (Hôpital Saint Eloi, Montpellier, France), Karl Barange, Christophe Bureau, Jean Marie Peron, Marie Angèle Robic, Léa Tarallo (CHU Purpan, Toulouse, France), Marine Faure, Bruno Froissart, Marie-Noelle Hilleret, Vincent Leroy (CHU de Grenoble, Grenoble, France), Odile Goria, Victorien Grard, Hélène Montialoux (CHU Charles Nicolle, Rouen, France), Muriel François, Christian Ouedraogo, Christelle Pauleau, Anne Varault (Hôpital Henri Mondor, Créteil, France), Tony Andreani, Bénédicte Angoulevant, Azeline Chevance, Lawrence Serfaty (Hôpital Saint-Antoine, Paris, France), Teresa Antonini, Audrey Coilly, Jean-Charles Duclos Vallée, Mariagrazia Tateo (Hôpital Paul Brousse, Villejuif, France), Armand Abergel, Corinne Bonny, Chanteranne Brigitte, Géraldine Lamblin, Léon Muti (Hôpital Estaing, Clermont-Ferrand, France), Abdenour Babouri, Virginie Filipe (Centre Hospitalier Régional, Metz, France), Camille Barrault, Laurent Costes, Hervé Hagège, Soraya Merbah (Centre Hospitalier Intercommunal, Créteil, France), Paul Carrier, Maryline Debette-Gratien, Jérémie Jacques (CHU Limoges, Limoges, France), Florent Artu, Valérie Canva, Sébastien Dharancy, Alexandre Louvet (CHRU Claude Huriez, Lille, France), Marc Bardou, Donya Da Costa Souhiel, Patrick Hillon, Marianne Latournerie (Dijon University Hospital, Dijon, France), Yannick Bacq, Didier Barbereau, Charlotte Nicolas (CHU Trousseau, 37 044 Tours, France), Nisserine Ben Amara, Danièle Botta-Fridlund, Isabelle Portal (CHU Timone, Marseille, France), Moana Gelu-Simeon and Marie-Josée Lafrance (CHU de Pointe-à-Pitre, Pointe-à-Pitre, Guadeloupe)., Université Paris Descartes - Paris 5 (UPD5), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, [SDV]Life Sciences [q-bio], Hepacivirus, Antiviral Agents, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Central Asia, Chronic hepatitis, Interquartile range, medicine, Humans, Prospective Studies, Poisson regression, Prospective cohort study, Socioeconomic status, direct-acting antivirals, Aged, Transients and Migrants, Hepatology, business.industry, virus diseases, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, 3. Good health, migrant, Cross-Sectional Studies, vulnerable population, 030220 oncology & carcinogenesis, symbols, Population study, population characteristics, 030211 gastroenterology & hepatology, France, hepatitis C, sustained virological response, business, Social vulnerability, Demography
Abstract

International audience; Despite universal health coverage in France, migrants face specific socioeconomic barriers that increase the likelihood of a suboptimal cascade of care for chronic hepatitis C virus (HCV) infection and impaired treatment effectiveness in this sub-population. We selected data collected from 2012 to 2018 from the ANRS CO22 HEPATHER prospective cohort study for chronic HCV participants with available data on treatment failure (defined as the presence of a detectable HCV-RNA load 12 weeks after their first DAA treatment ended). We performed multivariable Poisson regression models to test whether treatment failure rates differed significantly between HCV-infected migrants and non-migrants receiving DAA in France (cross-sectional analysis), while taking into account the former's world region of birth and other potential social vulnerability factors. Among the study population's 7,879 patients, 5,829 (74%) were non-migrants and 2,050 (26%) migrants. Median [interquartile range] age was 57 [51-65] years, 4433 (56%) were men and 369 (5%) of the entire study population had treatment failure. After multivariable adjustment, only migrants from Central Asia were at higher risk of treatment failure than non-migrants (aIRR = 2.83; 95% CI [1.72, 4.65]). Results from this large-scale study performed in France suggest a higher risk of DAA treatment failure in migrants from Central Asia than in non-migrants and confirm the overall low treatment failure rate in chronic HCV patients treated with DAA (whether migrants or not). Simplified models of care taking into account language and cultural barriers are needed to improve DAA effectiveness in migrants from Central Asia.

Published
2021
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46. Cannabis use is associated with a lower risk of diabetes in chronic hepatitis C-infected patients (ANRS CO22 Hepather cohort)

Author

Barré, Tangui, Nishimwe, Marie Libérée, Protopopescu, Camelia, Marcellin, Fabienne, Carrat, Fabrice, Dorival, Céline, Delarocque-Astagneau, Elisabeth, Larrey, Dominique G., Bourlière, Marc, Petrov-Sanchez, Ventzislava, Simony, Mélanie, Pol, Stanislas, Fontaine, Hélène, Carrieri, Patrizia Maria, Pageaux, Georges Philippe, HAL UVSQ, Équipe, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Biostatistique, Biomathématique, Pharmacoépidémiologie et Maladies Infectieuses (B2PHI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), 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), 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), Merck Sharp and Dohme, MSD Agence Nationale de la Recherche, ANR AbbVie Bristol-Myers Squibb, BMS AbbVie Association Française pour l'Etude du Foie, AFEF Roche Gilead Sciences Shionogi Cilag MSD France, FC reports grants from INSERM-ANRS, during the conduct of the study, and personal fees from Imaxio, outside the submitted work. MB reports grants and personal fees from AbbVie and Gilead, outside the submitted work, and personal fees from MSD, Janssen, Boehringher Ingelheim, Intercept, and Bristol-Myers Squibb, outside the submitted work. SP has received consulting and lecturing fees from Bristol-Myers Squibb, Janssen, Gilead, Roche, MSD, MYR-Pharma, Shionogi, Biotest and Abbvie, as well as grants from Bristol-Myers Squibb, Gilead, Roche and MSD. HF reports personal fees and invitations for medical meetings from Gilead, AbbVie, Bristol-Myers Squibb, MSD, and Janssen, outside the submitted work. Other authors declare no financial support. The cohort received financial support from the INSERM-ANRS (France Recherche Nord & Sud Sida-HIV H?patites), the French ANR (Agence Nationale de la Recherche), the French DGS (Direction Générale de la Santé), Merck Sharp and Dohme, Janssen-Cilag, Gilead, Abbvie, Bristol-Myers Squibb, and Roche. Those funding sources had no role in the writing of the manuscript or the decision to submit it for publication. We thank the study participants and the participating clinicians at each site. We also thank the INSERM-ANRS for sponsoring, funding and conducting the ANRS CO22 Hepather cohort in collaboration with the French Association for the Study of the Liver (Association Fran?aise pour l'Etude du Foie: AFEF). Finally, our thanks to Jude Sweeney for the English revision and editing of our manuscript., On behalf of the ANRS/AFEF Hepather study group : Delphine Bonnet, Virginie Sicart (CHU Purpan, Toulouse, France), François Bailly, Marjolaine Beaudoin, Dominique Giboz, Kerstin Hartig‐Lavie, Marianne Maynard (Hospices Civils de Lyon, Lyon, France), Morane Cavellec, Marjorie Cheraud‐Carpentier, François Raffi, Florian Vivrel (Hôpital Hôtel‐Dieu, Nantes, France), Jaouad Benhida, Jérôme Boursier, Paul Calès, Françoise Lunel, Frédéric Oberti (CHU Angers, Angers, France), Nathalie Boyer, Audrey Gilibert, Nathalie Giuily (Hôpital Beaujon, Clichy, France), Giovanna Scoazec (Hôpital Beaujon, Clichy, France and Hôpital Henri Mondor, Créteil, France), Sandrine Fernandes, Sylvie Keser, Philippe Sultanik, Anaïs Vallet‐Pichard (Hôpital Cochin, Paris, France), Juliette Foucher, Jean‐Baptiste Hiriart, Aurore Mathias, Julien Vergniol (Hôpital Haut‐Lévêque, Pessac, Bordeaux, France), Chrystelle Ansaldi, Laëtitia Chouquet, Emilie De Luca, Valérie Oules (Hôpital Saint Joseph, Marseille, France), Rodolphe Anty, Eve Gelsi, Régine Truchi (CHU de Nice, Nice, France), Elena Luckina, Nadia Messaoudi, Joseph Moussali, (Groupe Hospitalier Pitié‐Salpétrière, Paris, France), Barbara De Dieuleveult, Damien Labarriere, Pascal Poter, Si Nafa Si Ahmed (CHR La Source, Orléans, France), Nathalie Ganne‐Carrié, Véronique Grando‐Lemaire, Pierre Nahon, Alan Peltier, Judith Ung (Hôpital Jean Verdier, Bondy, France), Mariette Gougeon, Anne Guillygomarch, Caroline Jezequel (CHU Rennes, Rennes, France), Romain Moirand, Thomas F. Baumert, Michel Dofföel, Catherine Mutter, Pauline Simo‐Noumbissie (Hôpitaux Universitaires de Strasbourg, Strasbourg, France), Hélène Barraud, Mouni Bensenane, Abdelbasset Nani, Sarah Hassani‐Nani (CHU de Nancy, Vandoeuvre‐lès‐Nancy, France), Marie‐Albertine Bernard (CHU de Nancy, Vandoeuvre‐lès‐Nancy, France and Centre Hospitalier Régional, Metz, France), Michael Bismuth, Ludovic Caillo, Stéphanie Faure, Georges‐Philippe Pageaux, Marie Pierre Ripault (Hôpital Saint Eloi, Montpellier, France), Karl Barange, Christophe Bureau, Jean Marie Peron, Marie Angèle Robic, Léa Tarallo (CHU Purpan, Toulouse, France), Marine Faure, Bruno Froissart, Marie‐Noelle Hilleret, Vincent Leroy (CHU de Grenoble, Grenoble, France), Odile Goria, Victorien Grard, Hélène Montialoux (CHU Charles Nicolle, Rouen, France), Muriel François, Christian Ouedraogo, Christelle Pauleau, Anne Varault (Hôpital Henri Mondor, Créteil, France), Tony Andreani, Bénédicte Angoulevant, Azeline Chevance, Lawrence Serfaty (Hôpital Saint‐Antoine, Paris, France), Teresa Antonini, Audrey Coilly, Jean‐Charles Duclos Vallée, Mariagrazia Tateo (Hôpital Paul Brousse, Villejuif, France), Armand Abergel, Corinne Bonny, Chanteranne Brigitte, Géraldine Lamblin, Léon Muti (Hôpital Estaing, Clermont‐Ferrand, France), Abdenour Babouri, Virginie Filipe (Centre Hospitalier Régional, Metz, France), Camille Barrault, Laurent Costes, Hervé Hagège, Soraya Merbah (Centre Hospitalier Intercommunal, Créteil, France), Paul Carrier, Maryline Debette‐Gratien, Jérémie Jacques (CHU Limoges, Limoges, France), Florent Artu, Valérie Canva, Sébastien Dharancy, Alexandre Louvet (CHRU Claude Huriez, Lille, France), Marc Bardou, Donya Da Costa Souhiel, Patrick Hillon, Marianne Latournerie (Dijon University Hospital, Dijon, France), Yannick Bacq, Didier Barbereau, Charlotte Nicolas (CHU Trousseau, 37044 Tours, France), Nisserine Ben Amara, Danièle Botta‐Fridlund, Isabelle Portal (CHU Timone, Marseille, France), Moana Gelu‐Simeon, Marie‐Josée Lafrance (CHU de Pointe‐à‐Pitre, Pointe‐à‐Pitre, Guadeloupe)., Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Eloi, 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
Liver Cirrhosis, cannabis, medicine.medical_specialty, Population, HIV Infections, 030209 endocrinology & metabolism, marijuana smoking, Lower risk, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Diabetes mellitus, Internal medicine, medicine, Humans, Risk factor, education, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, education.field_of_study, Hepatology, biology, business.industry, 1. No poverty, Hepatitis C, Hepatitis C, Chronic, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, biology.organism_classification, 3. Good health, chronic, Cross-Sectional Studies, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cohort, diabetes mellitus, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030211 gastroenterology & hepatology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Cannabis, France, business
Abstract

International audience; Chronic hepatitis C virus (HCV) infection is a risk factor of insulin resistance, and HCV-infected patients are at a high risk of developing diabetes. In the general population, research has shown the potential benefit of cannabis use for the prevention of diabetes and related metabolic disorders. We aimed to test whether cannabis use is associated with a lower risk of diabetes in chronic HCV-infected patients. Chronic HCV-infected patients (n = 10 445) were selected from the French national, multicenter, observational ANRS CO22 Hepather cohort. Cross-sectional data collected at cohort enrollment were used to assess the association between patients’ clinical and behavioural characteristics and the risk of diabetes. Logistic regression model was performed with cannabis use as the main independent variable and a significance level set at 5%. A similar model stratified by the presence of advanced liver fibrosis (FIB-4 > 3.25) was also run. After multivariable adjustment, current (AOR [95%CI]: 0.49 [0.38-0.63]) and former (0.81 [0.67-0.98], P

Published
2020
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