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

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• 作者：Stanislas Pol¹ ; ^{stanislas.pol@aphp.fr} ; Marc Bourliere² ; Sandy Lucier³ ; Christophe Hezode⁴ ; C&eacute ; line Dorival³ ; Dominique Larrey⁵ ; Jean-Pierre Bronowicki⁶ ; Victor D.E. Ledinghen⁷ ; ⁸ ; Fabien Zoulim⁹ ; Albert Tran¹⁰ ; Sophie Metivier¹¹ ; Jean-Pierre Zarski¹² ; Didier Samuel¹³ ; Dominique Guyader¹⁴ ; Patrick Marcellin¹⁵ ; Anne Minello¹⁶ ; Laurent Alric¹⁷ ; Dominique Thabut¹⁸ ; Olivier Chazouilleres¹⁹ ; Ghassan Riachi²⁰ ; Val&eacute ; rie Bourcier²¹ ; Philippe Mathurin²² ; V&eacute ; ronique Loustaud-Ratti²³ ; Louis D&rsquo ; Alteroche²⁴ ; Isabelle Fouchard-Hubert²⁵ ; Franç ; ois Habersetzer²⁶ ; Xavier Causse²⁷ ; Claire Geist²⁸ ; Isabelle Rosa²⁹ ; J&eacute ; rô ; me Gournay³⁰ ; Eric Saillard³¹ ; Eric Billaud³² ; Ventzislava Petrov-Sanchez³³ ; Alpha Diallo³⁴ ; H&eacute ; lè ; ne Fontaine¹ ; Fabrice Carrat³ ; ³⁵ ; on behalf of the ANRS/AFEF HEPATHER study group
• 关键词：Chronic hepatitis C ; Treatment ; Sofosbuvir ; Daclatasvir ; Direct antiviral agents ; Cirrhosis ; Severe fibrosis ; Genotype 1 ; Hepather cohort
• 刊名：Journal of Hepatology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：66
• 期：1
• 页码：39-47
• 全文大小：798 K
• 卷排序：66

文摘

We report the first real-life results of the sofosbuvir + daclatasvir combination in hepatitis C virus (HCV) genotype 1 infected patients.MethodsThe 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 (400 mg/day) and daclatasvir (60 mg/day) before October 1st 2014, with or without ribavirin (1–1.2 g/day) for a duration of 12 weeks or 24 weeks. The main endpoint criterion was sustained virological response at 12 weeks (SVR12), defined by the absence of detectable HCV-RNA 12 weeks after the last treatment intake. Missing SVR12 measurements were imputed using SVR24 measurements (n = 45), otherwise considered as virological failure (n = 18).ResultsA 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).ConclusionThe sofosbuvir + daclatasvir combination is associated with a high rate of SVR12 in patients infected by genotype 1, with an optimal duration of 12 weeks in non-cirrhotic and 24 weeks in cirrhotic patients. The number of patients receiving ribavirin was too low to adequately assess its impact.Lay summaryThe 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 12 weeks in non-cirrhotic patients and 24 weeks for those with cirrhosis.Clinical trial number: NCT01953458.