Safety and efficacy of daclatasvir-sofosbuvir in HCV genotype 1-mono-infected patients

Stanislas Pol (1, 2) , Marc Bourlière (3) , Sandy Lucier (4) , Christophe Hézode (5, 6) , Céline Dorival (4) , Dominique Larrey (7, 8, 9) , Jean-Pierre Bronowicki (10, 11) , Victor D. E. Ledinghen (12) , Fabien Zoulim (13) , Albert Tran (14) , Sophie Metivier (15) , Jean-Pierre Zarski (16, 17) , Didier Samuel (18) , Dominique Guyader (19) , Patrick Marcellin (20) , Anne Minello (21, 22) , Laurent Alric (23) , Dominique Thabut (24, 25) , Olivier Chazouillères (26, 25) , Ghassan Riachi (27) , Valérie Bourcier (28) , Philippe Mathurin (29) , Véronique Loustaud-Ratti (30, 31) , Louis D’alteroche (32) , Isabelle Fouchard-Hubert (33, 34) , François Habersetzer (35) , Xavier Causse (36) , Claire Geist (37) , Isabelle Rosa (38) , Jérôme Gournay (39, 40) , Eric Saillard (41) , Eric Billaud (42) , Ventzislava Petrov-Sanchez (43) , Alpha Diallo (43) , Hélène Fontaine (1) , Fabrice Carrat (4)

1 Service d'hépatologie médicale [CHU Cochin]
2 Nutrition et cerveau (U1213, U855)
3 Hôpital Saint-Joseph [Marseille]
4 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
5 Inserm U955 - Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18)
6 Service d'hépato-gastro-entérologie [APHP Henri Mondor]
7 Cellules souches normales et cancéreuses
8 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
9 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
10 Service d'Hépato-gastro-entérologie [CHRU Nancy]
11 NGERE - Nutrition-Génétique et Exposition aux Risques Environnementaux
12 Physiopathologie du cancer du foie
13 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
14 C3M - Centre méditerranéen de médecine moléculaire
15 Pôle Maladies de l'appareil digestif [CHU Toulouse]
16 Département d'hépato-gastroentérologie
17 INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble
18 Physiopathologie et traitement des maladies du foie
19 Foie, métabolismes et cancer
20 Service d’Hépatologie [Hôpital Beaujon]
21 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
22 Service d'Hépato-Gastro-Entérologie (CHU de Dijon)
23 PHARMA-DEV - Pharmacochimie et Biologie pour le Développement
24 Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière]
25 UMRS893 - Centre de Recherche Saint-Antoine
26 Service d'hépatologie [CHU Saint-Antoine]
27 Service d'Hépato-Gastroentérologie [CHU Rouen]
28 Hôpital Jean Verdier [AP-HP]
29 CHRU Lille - Centre Hospitalier Régional Universitaire [Lille]
30 PIST - Pharmacologie des Immunosuppresseurs et de la Transplantation
31 Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges]
32 CHU Trousseau [Tours]
33 CHU Angers - Centre Hospitalier Universitaire d'Angers
34 HIFIH - Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques
35 Interactions Virus-Hôte et Maladies Hépatiques
36 CHRO - Centre Hospitalier Régional d'Orléans
37 CHR Metz-Thionville - Centre hospitalier régional Metz-Thionville
38 CHIC - Centre Hospitalier Intercommunal de Créteil
39 Hôtel-Dieu de Nantes
40 CHU Nantes - Centre hospitalier universitaire de Nantes
41 CHU Pointe-à-Pitre/Abymes [Guadeloupe]
42 Service des maladies infectieuses et tropicales [CHU Nantes]
43 ANRS France Recherche Nord & sud Sida-hiv hépatites

Background & aims - We report the first real-life results of the sofosbuvir+daclatasvir combination in hepatitis C virus (HCV) genotype 1 infected patients. Methods - The France REcherche Nord&Sud Sida-hiv Hépatites (ANRS) CO22 HEPATHER "Therapeutic options for hepatitis B and C: A French cohort" is a multicentre observational cohort which aims to include 15,000 HCV- and 10,000 HBV-infected patients. We selected all participants (n=768) with a HCV genotype 1 who initiated sofosbuvir (400mg/day) and daclatasvir (60mg/day) before October 1st 2014, with or without ribavirin (1-1.2g/day) for a duration of 12weeks or 24weeks. The main endpoint criterion was sustained virological response at 12weeks (SVR12), defined by the absence of detectable HCV-RNA 12weeks after the last treatment intake. Missing SVR12 measurements were imputed using SVR24 measurements (n=45), otherwise considered as virological failure (n=18). Results - A SVR12 was obtained in 729/768 (95%) patients, ranging from 92% (12-week sofosbuvir+daclatasvir) to 99% (24-week sofosbuvir+daclatasvir+ribavirin). The SVR12 rates did not significantly differ between the 24-week (550/574 (96%)) and the 12-week (179/194 (92%); p=0.0688) durations or between regimens with (165/169 (98%)) or without ribavirin (564/599 (94%); p=0.0850). The SVR12 rate was greater than 97% in non-cirrhotic patients irrespective of the treatment duration or the addition of ribavirin. Among cirrhotic patients, the SVR12 rate was higher with 24 than 12-week regimen (423/444 (95%) vs. 105/119 (88%); p=0.0054). Conclusion - The sofosbuvir+daclatasvir combination is associated with a high rate of SVR12 in patients infected by genotype 1, with an optimal duration of 12weeks in non-cirrhotic and 24weeks in cirrhotic patients. The number of patients receiving ribavirin was too low to adequately assess its impact. Lay summary - The sofosbuvir+daclatasvir combination of antiviral drugs is associated with a high rate (95%) of viral eradication in patients infected by HCV genotype 1. The best duration of a ribavirin-free sofosbuvir+daclatasvir combination seems to be 12weeks in non-cirrhotic patients and 24weeks for those with cirrhosis. Clinical trial number: NCT01953458.

Keywords: Hepather cohort; Genotype 1; Sofosbuvir; Treatment; Chronic hepatitis C; Severe fibrosis; Cirrhosis; Direct antiviral agents; Daclatasvir

Domains: Life Sciences [q-bio]; Pharmaceutical sciences; Pharmacology; Life Sciences [q-bio]; Human health and pathology; Infectious diseases; Life Sciences [q-bio]; Human health and pathology; Hépatology and Gastroenterology

Stanislas Pol, Marc Bourlière, Sandy Lucier, Christophe Hézode, Céline Dorival, et al.. Safety and efficacy of daclatasvir-sofosbuvir in HCV genotype 1-mono-infected patients. Journal of Hepatology, 2017, 66 (1), pp.39-47. ⟨10.1016/j.jhep.2016.08.021⟩. ⟨hal-01435007⟩