Title :

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

Author(s) :

Carrat, Fabrice [Auteur]
Institut Pierre Louis d'Epidémiologie et de Santé Publique [iPLESP]
Fontaine, Helene [Auteur]
Dorival, Celine [Auteur]
Institut Pierre Louis d'Epidémiologie et de Santé Publique [iPLESP]
Simony, Melanie [Auteur]
Agence Nationale de Recherches sur le Sida et les Hépatites Virales [ANRS]
Diallo, Alpha [Auteur]
Hezode, Christophe [Auteur]
Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) [Inserm U955]
De Ledinghen, Victor [Auteur]
Université de Bordeaux Ségalen [Bordeaux 2]
Larrey, Dominique [Auteur]
Haour, Georges [Auteur]
Institut Pierre Louis d'Epidémiologie et de Santé Publique [iPLESP]
Bronowicki, Jean-Pierre [Auteur]
Université de Lorraine [UL]
Zoulim, Fabien [Auteur]
Asselah, Tarik [Auteur]
Université Paris Diderot - Paris 7 [UPD7]
Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)]
Marcellin, Patrick [Auteur]
Université Paris Diderot - Paris 7 [UPD7]
Thabut, Dominique [Auteur]
Leroy, Vincent [Auteur]
Université Grenoble Alpes [2016-2019] [UGA [2016-2019]]
Tran, Albert [Auteur]
Habersetzer, Francois [Auteur]
Université de Strasbourg [UNISTRA]
Samuel, Didier [Auteur]
Université Paris-Sud - Paris 11 [UP11]
Guyader, Dominique [Auteur]
Université de Rennes [UR]
Chazouilleres, Olivier [Auteur]
Mathurin, Philippe [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Metivier, Sophie [Auteur]
Alric, Laurent [Auteur]
Immunologie et virologie des cancers. Immunologie des interactions cellulaires et moléculaires [Inserm U152]
Riachi, Ghassan [Auteur]
Gournay, Jerome [Auteur]
Abergel, Armand [Auteur]
Image Science for Interventional Techniques [ISIT]
Cales, Paul [Auteur]
Ganne, Nathalie [Auteur]
Génomique Fonctionnelle des Tumeurs Solides [U1162]
Université Paris 13 [UP13]
Loustaud-Ratti, Veronique [Auteur]
Université de Limoges [UNILIM]
D'alteroche, Louis [Auteur]
Causse, Xavier [Auteur]
Geist, Claire [Auteur]
Minello, Anne [Auteur]
Lipides - Nutrition - Cancer [Dijon - U1231] [LNC]
Rosa, Isabelle [Auteur]
Gelu-Simeon, Moana [Auteur]
Institut de recherche en santé, environnement et travail [Irset]
Portal, Isabelle [Auteur]
Raffi, Francois [Auteur]
Bourliere, Marc [Auteur]
Pol, Stanislas [Auteur]
Université Paris Descartes - Paris 5 [UPD5]

Journal title :

The Lancet

Abbreviated title :

Lancet

Volume number :

393

Pages :

1453-1464

Publication date :

2019-04-06

ISSN :

1474-547X

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

BACKGROUND: 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 ...
Show more >BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. BACKGROUND: INSERM-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.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
Inserm
Université de Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Submission date :

2019-10-22T08:09:25Z
2023-12-15T09:46:38Z