• Fabrice Carrat, Hélène Fontaine, Céline Dorival, Mélanie Simony, Alpha Diallo, Christophe Hezode, Victor De Ledinghen, Dominique Larrey, Georges Haour, Jean-Pierre Bronowicki, Fabien Zoulim, Tarik Asselah, Patrick Marcellin, Dominique Thabut, Vincent Leroy, Albert Tran, François Habersetzer, Didier Samuel, Dominique Guyader, Olivier Chazouilleres, Philippe Mathurin, Sophie Metivier, Laurent Alric, Ghassan Riachi, Jérôme Gournay, Armand Abergel, Paul Cales, Nathalie Ganne, Véronique Loustaud-Ratti, Louis D'Alteroche, Xavier Causse, Claire Geist, Anne Minello, Isabelle Rosa, Moana Gelu-Simeon, Isabelle Portal, François Raffi, Marc Bourliere, Stanislas Pol, and French ANRS CO22 Hepather cohort.
• Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France; Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Antoine, Unité de Santé Publique, Paris, France. Electronic address: fabrice.carrat@iplesp.upmc.fr.
• Lancet. 2019 Apr 6; 393 (10179): 1453-1464.

BackgroundAlthough 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.MethodsWe 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.FindingsBetween 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).InterpretationTreatment 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.FundingINSERM-ANRS (France Recherche Nord & Sud Sida-HIV Hépatites), ANR (Agence Nationale de la Recherche), DGS (Direction Générale de la Santé), MSD, Janssen, Gilead, AbbVie, Bristol-Myers Squibb, and Roche.Copyright © 2019 Elsevier Ltd. All rights reserved.

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