Sofosbuvir plus daclatasvir with or without ribavirin is safe and effective for post-transplant hepatitis C recurrence and severe fibrosis and cirrhosis: A prospective study.

In 2012, an Italian Named Patient Program began for hepatitis C virus (HCV)-infected liver transplant (LT) recipients with advanced fibrosis, before approval of direct antiviral agents (DAA), to benefit severely ill patients. The aim of this "real-life" study was to assess treatment efficacy and safety with an extended course of daclatasvir (DCV) plus sofosbuvir (SOF) with or without ribavirin (RBV). All HCV LT recipients with severe fibrosis in 15 Italian transplant centers were treated with DCV+SOF±RBV for 24 weeks; sustained virological response was assessed at 12 weeks post-treatment (SVR12). Eighty-seven patients were enrolled (75.9% males, mean age 58.4 ± 7.2 years, 83.9% genotype 1, 81.6% cirrhosis); 52 (59.8%) received RBV. Overall, 79 obtained SVR12 (90.8%): 100% in F3 and 88.7% in cirrhotics (91.5% in Child-Pugh A, 83.3% in Child-Pugh B and C). According to the treatment group, SVR was 80% in DCV + SOF group and 98.1% in SOF + DCV + RBV. Two virological relapses occurred during follow-up in cirrhotic patients who received DCV + SOF. Four cirrhotic patients in DCV + SOF group and 1 in DCV + SOF + RBV group died on treatment. An extended course of SOF plus DCV for 24 weeks, with or without RBV, is effective and well tolerated for the treatment of post-LT HCV recurrence with severe fibrosis.

Lionetti R ，Calvaruso V ，Piccolo P ，Mancusi RL ，Mazzarelli C ，Fagiuoli S ，Montalbano M ，Lenci I ，Carrai P ，Guaraldi G ，Visco-Comandini U ，Milana M ，Biolato M ，Loiacono L ，Valente G ，Craxì A ，Angelico M ，D'offizi G ... -  《-》

Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection.

Daclatasvir (DCV) is a potent, pangenotypic nonstructural protein 5A inhibitor with demonstrated antiviral efficacy when combined with sofosbuvir (SOF) or simeprevir (SMV) with or without ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection. Herein, we report efficacy and safety data for DCV-based all-oral antiviral therapy in liver transplantation (LT) recipients with severe recurrent HCV. DCV at 60 mg/day was administered for up to 24 weeks as part of a compassionate use protocol. The study included 97 LT recipients with a mean age of 59.3 ± 8.2 years; 93% had genotype 1 HCV and 31% had biopsy-proven cirrhosis between the time of LT and the initiation of DCV. The mean Model for End-Stage Liver Disease (MELD) score was 13.0 ± 6.0, and the proportion with Child-Turcotte-Pugh (CTP) A/B/C was 51%/31%/12%, respectively. Mean HCV RNA at DCV initiation was 14.3 × 6 log10 IU/mL, and 37% had severe cholestatic HCV infection. Antiviral regimens were selected by the local investigator and included DCV+SOF (n = 77), DCV+SMV (n = 18), and DCV+SMV+SOF (n = 2); 35% overall received RBV. At the end of treatment (EOT) and 12 weeks after EOT, 88 (91%) and 84 (87%) patients, respectively, were HCV RNA negative or had levels <43 IU/mL. CTP and MELD scores significantly improved between DCV-based treatment initiation and last contact. Three virological breakthroughs and 2 relapses occurred in patients treated with DCV+SMV with or without RBV. None of the 8 patient deaths (6 during and 2 after therapy) were attributed to therapy. In conclusion, DCV-based all-oral antiviral therapy was well tolerated and resulted in a high sustained virological response in LT recipients with severe recurrent HCV infection. Most treated patients experienced stabilization or improvement in their clinical status.

Fontana RJ ，Brown RS Jr ，Moreno-Zamora A ，Prieto M ，Joshi S ，Londoño MC ，Herzer K ，Chacko KR ，Stauber RE ，Knop V ，Jafri SM ，Castells L ，Ferenci P ，Torti C ，Durand CM ，Loiacono L ，Lionetti R ，Bahirwani R ，Weiland O ，Mubarak A ，ElSharkawy AM ，Stadler B ，Montalbano M ，Berg C ，Pellicelli AM ，Stenmark S ，Vekeman F ，Ionescu-Ittu R ，Emond B ，Reddy KR ... -  《-》

High Efficacy and Safety of Flat-Dose Ribavirin Plus Sofosbuvir/Daclatasvir in Genotype 3 Cirrhotic Patients.

Pellicelli A ，Messina V ，Giannelli V ，Distefano M ，Palitti VP ，Vignally P ，Tarquini P ，Izzi A ，Moretti A ，Babudieri S ，Dell'Isola S ，Marignani M ，Scifo G ，Iovinella V ，Cariti G ，Pompili M ，Candilo FD ，Fontanella L ，Ettorre GM ，Vennarecci G ，Ippolito AM ，Barbarini G ... -  《-》

Sofosbuvir plus Daclatasvir with or without ribavirin for treatment of chronic HCV genotype 4 patients: real-life experience.

Shiha G ，Soliman R ，ElBasiony M ，Hassan AA ，Mikhail NNH ... -  《-》

Real-world effectiveness of daclatasvir plus sofosbuvir and velpatasvir/sofosbuvir in hepatitis C genotype 2 and 3.

Understanding the real-world effectiveness of all-oral hepatitis C virus (HCV) regimens informs treatment decisions. We evaluated the effectiveness of daclatasvir + sofosbuvir ± ribavirin (DCV + SOF ± RBV) and velpatasvir/sofosbuvir (VEL/SOF) ± RBV in patients with genotype 2 and genotype 3 infection treated in routine practice. This observational analysis was carried out in an intent-to-treat cohort of patients with HCV genotype 2 and genotype 3. Sustained virologic response (SVR) analysis was performed in 5,400 patients initiated on DCV + SOF ± RBV or VEL/SOF ± RBV at any Department of Veterans Affairs facility. For genotype 2, SVR rates did not differ between DCV + SOF (94.5%) and VEL/SOF (94.4%) or between DCV + SOF + RBV (88.1%) and VEL/SOF + RBV (89.5%). For genotype 3, SVR rates did not differ between DCV + SOF (90.8%) and VEL/SOF (92.0%) or between DCV + SOF + RBV (88.1%) and VEL/SOF + RBV (86.4%). In multivariate models of patients with genotype 2 and 3 infection, the treatment regimen was not a significant predictor of the odds of SVR. For genotype 3, significant predictors of reduced odds of SVR were prior HCV treatment-experience (odds ratio [OR] 0.51, 95% CI 0.36-0.72; p <0.001), FIB-4 >3.25 (OR 0.60; 95%CI 0.43-0.84; p = 0.002) and a history of decompensated liver disease (OR 0.68; 95%CI 0.47-0.98; p = 0.04). For patients with genotype 2 and 3, treated with VEL/SOF ± RBV, 89% and 85% received 12-weeks of treatment, respectively. For DCV + SOF ± RBV, 56% and 20% of patients with HCV genotype 2 received 12-weeks and 24-weeks of treatment, respectively; while 53% and 23% of patients with HCV genotype 3 received 12-weeks and 24-weeks, with most direct-acting antiviral experienced patients receiving 24-weeks. In patients infected with HCV genotype 2 and 3, DCV + SOF ± RBV and VEL/SOF ± RBV produced similar SVR rates within each genotype, and the regimen did not have a significant impact on the odds of SVR. For patients with genotype 3, prior treatment-experience and advanced liver disease were significant predictors of reduced odds of SVR regardless of regimen. In clinical practice, cure rates for hepatitis C virus (HCV) genotype 2 were 94% and cure rates for HCV genotype 3 were 90%. The chance of achieving cure was the same whether a person received daclatasvir plus sofosbuvir or velpatasvir/sofosbuvir. Ribavirin did not affect cure rates. The chance of a cure was lowest in people who had received HCV medication in the past.

Belperio PS ，Shahoumian TA ，Loomis TP ，Mole LA ，Backus LI ... -  《-》