Effectiveness and safety of daclatasvir/sofosbuvir with or without ribavirin in genotype 3 hepatitis C virus infected patients. Results in real clinical practice.

Direct-acting antivirals have shown high efficacy in all hepatitis C virus (HCV) genotypes, but genotype 3 (G3) treatments continue to be a challenge, mainly in cirrhotic patients. The aim of this study is to analyse effectiveness and safety of daclatasvir associated with sofosbuvir with or without ribavirin in G3-HCV infected patients in real clinical practice. An observational, prospective, cohort study over 2.5 years, in G3-HCV infected adult patients, in all fibrosis stages including patients with decompensated cirrhosis. Treatment was a combination of sofosbuvir 400 mg/day + daclatasvir 60 mg/day, with or without a weight-adjusted dosing of ribavirin for 12 or 24 weeks. The primary efficacy endpoint was sustained virologic response rates 12 weeks after therapy (SVR12). The primary safety endpoint was treatment withdrawal rates secondary to severe adverse events. A total of 111 patients were enrolled, 32.4% cirrhotics and 29.9% treatment-experienced. The global SVR12 rate was 94.6%, while the SVR12 rate in F3-4 fibrosis stage patients was 90.8% versus 100% in patients with F0-2 fibrosis (p=0.03). In cirrhotic patients, SVR12 was 100% versus 40% depending on whether ribavirin was added or not to daclatasvir/sofosbuvir (p=0.001). No other patient or treatment basal variables influenced the treatment effectiveness. No patient treatment withdrawal secondary to severe adverse events was observed. Daclatasvir/sofosbuvir ± ribavirin is highly effective in G3-HCV infected patients. Advanced degrees of fibrosis significantly decrease the effectiveness of this treatment, which motivates the need for the addition of ribavirin in cirrhotic patients. The regimen was safe and well tolerated.

Margusino-Framiñán L ，Cid-Silva P ，Mena-de-Cea A ，Rodríguez-Osorio I ，Pernas-Souto B ，Delgado-Blanco M ，Pertega-Díaz S ，Martín-Herranz I ，Castro-Iglesias A ... -  《-》

Direct-acting antiviral agents in the treatment of chronic hepatitis C-Real-life experience from clinical practices in Pakistan.

This study aims to evaluate the clinical effectiveness in terms of sustained virological response (SVR), predictors of SVR and safety of available second-generation generic direct-acting antivirals in Pakistani chronic hepatitis C patients. This is a retrospective study conducted in multiple centers of Pakistan from January 2015 to January 2019. The samples include patients infected with chronic hepatitis C virus, regardless of virus genotype, cirrhosis, or prior treatment. A total of 993 patients were included in the present study, with the majority receiving sofosbuvir with daclatasvir (95%), sofosbuvir with daclatasvir and ribavirin (4%), and sofosbuvir with ribavirin (1%). There were 96% cases of chronic hepatitis, 3% cases compensated cirrhosis, and 1% cases of decompensated cirrhosis. Genotype 3 (99.6%) was the most common genotype. Overall SVR after 12 weeks was 98% for all treatment regimens. High SVR12 was observed with sofosbuvir in combination with daclatasvir (98.5%), then sofosbuvir in combination with daclatasvir and ribavirin (90.2%) and sofosbuvir in combination with ribavirin (75%). SVR rates were high in chronic hepatitis C patients (98.2%) as compared with cirrhotic patients (92.1%) and it was high in treatment-naive (98.8%) then interferon experienced patients (90.1%). In multivariate binary logistic regression analysis, patients' education status, treatment strategy, viral load, and alanine aminotransferase had a statistically significant association with SVR at 12 weeks. No major adverse events occurred which required treatment discontinuation. Generic oral direct acting antiviralss (sofosbuvir with daclatasvir) achieved higher SVR12 rates and were well tolerated in this large real-world cohort of genotype 3 infected patients.

Mushtaq S ，Mansoor A ，Umar M ，Khan A ，Siddiqi S ，Manzoor S ... -  《-》

Daclatasvir plus sofosbuvir, with or without ribavirin, for hepatitis C virus genotype 3 in a French early access programme.

Optimally effective treatment for hepatitis C virus genotype 3 (GT3) is urgently needed, particularly in advanced liver disease. Daclatasvir plus sofosbuvir was efficacious in phase 3 studies. Real-world data for daclatasvir+sofosbuvir in advanced GT3 infection are presented from the French Temporary Authorisation for Use programme, which allowed patients in need without other treatment options access to daclatasvir ahead of its market authorization. Patients with F3/F4 fibrosis and/or extrahepatic hepatitis C virus manifestations, post-liver transplant hepatitis C virus recurrence and/or indication for liver/kidney transplant, were treated with daclatasvir+sofosbuvir (60+400 mg daily) for a recommended duration of 24 weeks. Addition of ribavirin and/or shorter treatment was at physician's discretion. The primary efficacy analysis was sustained virological response at post-treatment week 12 (SVR12; modified intention-to-treat). Safety was assessed by spontaneous adverse event reporting. The efficacy population comprised 333 patients, mostly cirrhotic (77%, of whom 18% were decompensated) and treatment experienced (72%). After 24 weeks of daclatasvir+sofosbuvir, SVR12 was 89% (174/196) overall (95% CI 83.6-92.5%), 98% (43/44) without cirrhosis (95% CI 88.2-99.6%) and 86% (129/150) with any degree of cirrhosis (95% CI 79.5-90.7%), without SVR12 increase in those who received additional ribavirin for 24 weeks (SVR12 82% [50/61; 95% CI 70.5-89.6%]). Among 516 GT3-infected patients with safety data, 5 discontinued for adverse events and 11 died. Daclatasvir+sofosbuvir achieved high SVR12 rates and was well tolerated in this large real-world cohort of GT3-infected patients with advanced liver disease, without benefit of ribavirin in those treated 24 weeks.

Hézode C ，Lebray P ，De Ledinghen V ，Zoulim F ，Di Martino V ，Boyer N ，Larrey D ，Botta-Fridlund D ，Silvain C ，Fontaine H ，D'Alteroche L ，Leroy V ，Bourliere M ，Hubert-Fouchard I ，Guyader D ，Rosa I ，Nguyen-Khac E ，Fedchuk L ，Akremi R ，Bennai Y ，Filipovics A ，Zhao Y ，Bronowicki JP ... -  《-》

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.

Pol S ，Bourliere M ，Lucier S ，Hezode C ，Dorival C ，Larrey D ，Bronowicki JP ，Ledinghen VD ，Zoulim F ，Tran A ，Metivier S ，Zarski JP ，Samuel D ，Guyader D ，Marcellin P ，Minello A ，Alric L ，Thabut D ，Chazouilleres O ，Riachi G ，Bourcier V ，Mathurin P ，Loustaud-Ratti V ，D'Alteroche L ，Fouchard-Hubert I ，Habersetzer F ，Causse X ，Geist C ，Rosa I ，Gournay J ，Saillard E ，Billaud E ，Petrov-Sanchez V ，Diallo A ，Fontaine H ，Carrat F ，ANRS/AFEF HEPATHER study group ... -  《-》

High efficacy of resistance-guided retreatment of HCV patients failing NS5A inhibitors in the real world.

Pérez AB ，Chueca N ，García-Deltoro M ，Martínez-Sapiña AM ，Lara-Pérez MM ，García-Bujalance S ，Aldámiz-Echevarría T ，Vera-Méndez FJ ，Pineda JA ，Casado M ，Pascasio JM ，Salmerón J ，Alados-Arboledas JC ，Poyato A ，Téllez F ，Rivero-Juárez A ，Merino D ，Vivancos-Gallego MJ ，Rosales-Zábal JM ，García F ，GEHEP-004 Study Group ... -  《-》