Daclatasvir With Sofosbuvir and Ribavirin for HCV Infection With Advanced Cirrhosis or Post-Liver Transplant Recurrence.Poordad F, Schiff ER, Vierling JM, Landis C, Fontana RJ, Yang R, McPhee F, Hughes EA, Noviello S, Swenson ES. Hepatology. 2016 Jan 11. [Epub ahead of print]

Chronic hepatitis C virus (HCV) infection with advanced cirrhosis or post-liver transplant 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 once-daily daclatasvir 60 mg (pan-genotypic NS5A inhibitor) in combination with sofosbuvir 400 mg (NS5B inhibitor) and ribavirin 600 mg for 12 weeks with a 24 week follow-up in two cohorts of patients with chronic HCV (any genotype >) infection: those with compensated/decompensated cirrhosis or post-transplant recurrence. Patients with on-treatment transplantation could receive 12 additional weeks of treatment immediately post-transplant. The primary efficacy measure was sustained virologic response at post-treatment week 12 (SVR12) in patients with GT1 infection in each cohort. Sixty patients with advanced cirrhosis and 53 with post-transplant 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% CI 67.9-92.0) with GT1 infection achieved SVR12 while corresponding rates in those with GT 2, 3, and 4 were 80%, 83%, and 100%, respectively; SVR12 rates in were higher with Child-Pugh class A or B (93%) versus class C (56%). In transplant recipients, SVR12 was achieved by 95% (83.5-99.4) and 91% of patients with GT1 and GT3 infection, respectively. Three patients received peri-transplant 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 transplant recurrence or advanced cirrhosis.

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