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1. 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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2. 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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3. 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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4. 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

5. 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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6. 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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7. 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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8. 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

9. 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

10. 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

11. 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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12. 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

13. 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

14. 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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15. 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

16. 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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17. 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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18. 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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19. 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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20. 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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21. 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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22. 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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23. 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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24. Hépatite sub-fulminante mortelle secondaire à l'acétate de cyprotérone: à propos d'un cas

Author: Isabelle Portal, P Castellani, Christophe Renou, D Botta-Fridlund, C. Zamora, Bernardini D, and A Gautier
Subjects: Gastroenterology, Internal Medicine
Published: 1996
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25. 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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25 results on '"Isabelle Portal"'

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

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

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

4. Sofosbuvir plus ledipasvir in combination for the treatment of hepatitis C infection

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

6. 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

7. 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

8. Chronic hepatitis C: treatments of the future

9. Future treatment of patients with HCV cirrhosis

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

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

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

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

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

15. Covert transmission of hepatitis C virus during bloody fisticuffs

16. 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

17. P.363 Validation of hepascore for diagnosis of liver fibrosis in HCV patients and determination of a new algorithm

19. 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

20. 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

21. 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

22. 68 Independent prospective multicenter validation of biochemical markers (fibrotest-actitest) for the prediction of liver fibrosis and activity in patients with chronic hepatitis C

23. Retreatment with interferon-riravirine according to viremia of interferon responder-relapser patients: French multicenter randomized controlled study

24. Hépatite sub-fulminante mortelle secondaire à l'acétate de cyprotérone: à propos d'un cas

25. Liver fibrosis and all‐cause mortality in chronic HCV‐infected diabetic patients: A paradoxical association? (ANRS CO22 HEPATHER)

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