Safety and efficacy of daclatasvir-sofosbuvir in HCV genotype 1-mono-infected patients.
We report the first real-life results of the sofosbuvir+daclatasvir combination in hepatitis C virus (HCV) genotype 1 infected patients.



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).



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).



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.



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.
Université Paris Descartes, AP-HP, Unité d'Hépatologie, Hôpital Cochin, INSERM U-1213 et USM20, Institut Pasteur, Paris, France. Electronic address: stanislas.pol@aphp.fr.
Stanislas
S
Pol
Department of Hepatology and Gastroenterology, Hôpital Saint Joseph, Marseille, France.
Marc
M
Bourliere
Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), F75012 Paris, France.
Sandy
S
Lucier
Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, AP-HP, Université Paris-Est, INSERM U955, Créteil, France.
Christophe
C
Hezode
Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), F75012 Paris, France.
Céline
C
Dorival
Liver unit-IRB-INSERM1040, Hôpital Saint Eloi, Montpellier, France.
Dominique
D
Larrey
Department of Hepatology and Gastroenterology, Centre Hospitalier Universitaire de Nancy, Université de Lorraine, INSERM U954, Vandoeuvre-lès-nancy, France.
Jean-Pierre
JP
Bronowicki
Department of Hepatology and Gastroenterology, Hôpital Haut-Lévêque, Pessac, France; INSERM, U1053, Université Bordeaux Segalen, Bordeaux, France.
Victor D E
VD
Ledinghen
Department of Hepatology, Hospices Civils de Lyon, INSERM U1052, Université de Lyon, Lyon, France.
Fabien
F
Zoulim
Digestive Centre, Centre Hospitalier Universitaire de Nice, INSERM U1065-8, Nice, France.
Albert
A
Tran
Department of Hepatology and Gastroenterology, CHU Purpan, Toulouse, France.
Sophie
S
Metivier
Department of Hepatology and Gastroenterology, Centre Hospitalo-Universitaire, INSERM U823, Grenoble, France.
Jean-Pierre
JP
Zarski
Centre Hépato-Biliaire, Hôpital Paul Brousse, AP-HP, UMR-S785, Université Paris-Sud, INSERM U785, Villejuif, France.
Didier
D
Samuel
Liver Disease Unit, CHU Rennes, Université de Rennes 1, INSERM U991, Rennes, France.
Dominique
D
Guyader
Department of Hepatology, Hôpital Beaujon, AP-HP, Université Paris-Diderot, INSERM CRB3, Clichy, France.
Patrick
P
Marcellin
Department of Hepatology and Gastroenterology, Dijon University Hospital, Burgundy University, INSERM U866, France.
Anne
A
Minello
Internal Medicine-Digestive Department CHU Purpan, UMR152, IRD, Toulouse 3 University, France.
Laurent
L
Alric
Department of Hepatology and Gastroenterology, Groupe Hospitalier Pitié-Salpétrière, AP-HP, Université Pierre et Marie Curie Paris 6, INSERM UMR-S938, Paris, France.
Dominique
D
Thabut
Department of Hepatology, Hôpital Saint-Antoine, AP-HP, Université Pierre et Marie Curie Paris 6, Paris, France.
Olivier
O
Chazouilleres
Department of Hepatology and Gastroenterology, CHU Charles Nicolle, Rouen, France.
Ghassan
G
Riachi
Department of Hepatology and Gastroenterology, Hôpital Jean Verdier, AP-HP, Université Paris 13, Bondy, France.
Valérie
V
Bourcier
Department of Hepatology and Gastroenterology, Centre Hospitalier Régional et Universitaire Claude Huriez, Lille, France.
Philippe
P
Mathurin
Department of Hepatology and Gastroenterology, CHU Limoges, U850 INSERM, Univ. Limoges, F-87000 Limoges, France.
Véronique
V
Loustaud-Ratti
Unit of Hepatology, Hépatogastroenterologie, CHU Trousseau, 37044 Tours, France.
Louis
L
D'Alteroche
Liver-Gastroenterology Department, CHU Angers, France.
Isabelle
I
Fouchard-Hubert
Inserm CIC-1434, Inserm 1110 et Pôle Hépato-digestif des Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
François
F
Habersetzer
Department of Hepatology and Gastroenterology, CHR La Source, Orléans, France.
Xavier
X
Causse
Department of Hepatology and Gastroenterology, Centre Hospitalier Régional, Metz, France.
Claire
C
Geist
Department of Hepatology and Gastroenterology, Centre Hospitalier Intercommunal, Créteil, France.
Isabelle
I
Rosa
Department of Hepatology and Gastroenterology, Hôpital Hôtel-Dieu, Nantes, France.
Jérôme
J
Gournay
Department of Gastroenterology, CHU de Pointe-à-Pitre, Guadeloupe, France.
Eric
E
Saillard
Division of Infectious Diseases, University Hospital of Nantes, Nantes, France.
Eric
E
Billaud
ANRS (France REcherche Nord&sud Sida-vih Hépatites), Unit for Basic and Clinical Research on Viral Hepatitis, Paris, France.
Ventzislava
V
Petrov-Sanchez
ANRS (France REcherche Nord&sud Sida-vih Hépatites), Clinical Trial Safety and Public Health, Paris, France.
Alpha
A
Diallo
Université Paris Descartes, AP-HP, Unité d'Hépatologie, Hôpital Cochin, INSERM U-1213 et USM20, Institut Pasteur, Paris, France.
Hélène
H
Fontaine
Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), F75012 Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Unité de Santé Publique, F-75012 Paris, France.
Fabrice
F
Carrat
D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D002219:Carbamates; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005602:France / Q000453:epidemiology; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D012367:RNA, Viral / Q000032:analysis*; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects; D000069474:Sofosbuvir / Q000008:administration & dosage / Q000009:adverse effects; D000072230:Sustained Virologic Response; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives
D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D012367:RNA, Viral; D012254:Ribavirin; D014633:Valine; C549273:daclatasvir; D000069474:Sofosbuvir
Chronic hepatitis C; Cirrhosis; Daclatasvir; Direct antiviral agents; Genotype 1; Hepather cohort; Severe fibrosis; Sofosbuvir; Treatment