Daclatasvir with sofosbuvir and ribavirin for hepatitis C virus infection with advanced cirrhosis or post‐liver transplantation recurrence

Abstract

Chronic hepatitis C virus (HCV) infection with advanced cirrhosis or post‐liver transplantation recurrence represents a high unmet medical need with no approved therapies effective across all HCV genotypes. The open‐label ALLY‐1 study assessed the safety and efficacy of a 60‐mg once‐daily dosage of daclatasvir (pan‐genotypic NS5A inhibitor) in combination with sofosbuvir at 400 mg once daily (NS5B inhibitor) and ribavirin at 600 mg/day for 12 weeks with a 24‐week follow‐up in two cohorts of patients with chronic HCV infection of any genotype and either compensated/decompensated cirrhosis or posttransplantation recurrence. Patients with on‐treatment transplantation were eligible to receive 12 additional weeks of treatment immediately after transplantation. The primary efficacy measure was sustained virologic response at posttreatment week 12 (SVR12) in patients with a genotype 1 infection in each cohort. Sixty patients with advanced cirrhosis and 53 with posttransplantation recurrence were enrolled; HCV genotypes 1 (76%), 2, 3, 4, and 6 were represented. Child‐Pugh classifications in the advanced cirrhosis cohort were 20% A, 53% B, and 27% C. In patients with cirrhosis, 82% (95% confidence interval [CI], 67.9%‐92.0%) with genotype 1 infection achieved SVR12, whereas the corresponding rates in those with genotypes 2, 3, and 4 were 80%, 83%, and 100%, respectively; SVR12 rates were higher in patients with Child‐Pugh class A or B, 93%, versus class C, 56%. In transplant recipients, SVR12 was achieved by 95% (95% CI, 83.5%‐99.4%) and 91% of patients with genotype 1 and 3 infection, respectively. Three patients received peritransplantation treatment with minimal dose interruption and achieved SVR12. There were no treatment‐related serious adverse events. Conclusion: The pan‐genotypic combination of daclatasvir, sofosbuvir, and ribavirin was safe and well tolerated. High SVR rates across multiple HCV genotypes were achieved by patients with post‐liver transplantation recurrence or advanced cirrhosis. (Hepatology 2016;63:1493‐1505)

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

“…Therefore, the standard immunosuppression does not need any change with the DAAs described in this review. 67 The efficacy and safety data for DCV-based all-oral antiviral therapy in LT has been shown by Fontana et al 79 in 97 cases after LT [(DCV/SOF (n = 77), DCV/ simeprevir (n = 18), and DCV/SOF/simeprevir (n = 2)]. Overall, 35% of the patients received RBV.…”

“…As in most trials studying decompensated cirrhotics, the initial dose of RBV was 600 mg/day, and this was gradually escalated up to 1000 mg/day based on creatinine clearance values, as well as the hemoglobin values. 67 In the French early access program (EAP), SOF and DCV, with or without RBV, were given for 12 or 24 weeks. For SOF/DCV, SVR rate was higher in patients treated for 24 weeks rather than 12 weeks.…”

Paritaprevir-Ritonavir, Ombitasvir and Dasabuvir plus Ribavirin to Treat Hepatitis C Genotype 1 Infection after Liver Transplantation: A Single-Center Experience

“…Several studies have been published recently on sofosbuvir-based regimens combined with other DAAs in transplant recipients with genotype 1 infection. SVR rates at 12 weeks post-treatment were consistently higher than 85% (9,10).…”

“…These results were surpassed by other more effective combinations such as sofosbuvir and simprevir [9] or sofusbuvir and daclatasvir [10].…”

Sofosbuvir and velpatasvir: a stellar option for patients with decompensated hepatitis C virus (HCV) cirrhosis

“…The advent of highly effective direct acting antiviral (DAA) therapy in the management of these difficult-totreat chronic hepatitis C subpopulation has significantly improved sustained virologic response (SVR, absence of HCV RNA in plasma 12 weeks after cessation of therapy), while maintaining an excellent safety profile (3)(4)(5). Achieving SVR has resulted in reversal of the degree of fibrosis, reduction in the risk of hepatocellular carcinoma, lowers the rate of hepatic decompensation, and perhaps curtails the need for liver transplantation (2,6,7).…”