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

Stanislas Pol; Marc Bourlière; Sandy Lucier; Christophe Hézode; Céline Dorival; Dominique Larrey; Jean-Pierre Bronowicki; Victor D. E. Ledinghen; Fabien Zoulim; Albert Tran; Sophie Metivier; Jean-Pierre Zarski; Didier Samuel; Dominique Guyader; Patrick Marcellin; Anne Minello; Laurent Alric; Dominique Thabut; Olivier Chazouillères; Ghassan Riachi; Valérie Bourcier; Philippe Mathurin; Véronique Loustaud-Ratti; Louis D’alteroche; Isabelle Fouchard-Hubert; François Habersetzer; Xavier Causse; Claire Geist; Isabelle Rosa; Jérôme Gournay; Eric Saillard; Eric Billaud; Ventzislava Petrov-Sanchez; Alpha Diallo; Hélène Fontaine; Fabrice Carrat

doi:10.1016/j.jhep.2016.08.021

Journal articles

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

Stanislas Pol ^{1, *} Marc Bourlière ^{2, 3} Sandy Lucier ^{4, 5} Christophe Hézode ⁶ Céline Dorival ⁵ Dominique Larrey ^{7, 8} Jean-Pierre Bronowicki ^{9, 10} Victor D. E. Ledinghen ¹¹ Fabien Zoulim ¹² Albert Tran ¹³ Sophie Metivier ¹⁴ Jean-Pierre Zarski ^{15, 16} Didier Samuel ^{17, 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 Eric Saillard ⁴⁰ Eric Billaud ⁴¹ Ventzislava Petrov-Sanchez ⁴² Alpha Diallo ⁴² Hélène Fontaine ¹ Fabrice Carrat ⁵

* Corresponding author

1 Service d'hépatologie médicale [CHU Cochin]

2 Service d'hépato-gastro-entérologie

3 Hôpital Saint-Joseph [Marseille]

4 Département de la recherche clinique et du développement

5 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique

6 AP HP, Departement Gastroenterologie

7 CHU Saint-Eloi

8 Cellules souches normales et cancéreuses

9 Service d'Hépato-gastro-entérologie [CHRU Nancy]

10 NGERE - Nutrition-Génétique et Exposition aux Risques Environnementaux

11 Physiopathologie du cancer du foie

12 Centre de Recherche sur le Cancer de Lyon

13 C3M - Centre méditerranéen de médecine moléculaire

14 Service de Gastro-entérologie - Hépatologie [Purpan]

15 Département d'hépato-gastroentérologie

16 INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble

17 Physiopathologie et traitement des maladies du foie

18 Centre hépato-biliaire - CHB [Paul Brousse, Paris]

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-Gastroentérologie [CHU Pitié-Salpêtrière]

25 CR Saint-Antoine - Centre de Recherche Saint-Antoine

26 Service d'hépatologie [Saint-Antoine]

27 Service d'Hépato-Gastroentérologie [CHU Rouen]

28 Service d'Hépato-gastroentérologie

29 Service d'Hépato-gastroentérologie

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 Service Hépato-gastro-entérologie et oncologie digestive [CHR Orléans]

37 CHR Metz-Thionville - Centre hospitalier régional Metz-Thionville

38 Service d'hépato-gastro-entérologie

39 Service d'hépato-gastro-entérologie

40 CHU Pointe-à-Pitre/Abymes [Guadeloupe]

41 Service des maladies infectieuses [Nantes]

42 Recherches fondamentales, cliniques et thérapeutiques sur les hépatites virales

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

Document type :

Journal articles

Domain :

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

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

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

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