Ledipasvir-sofosbuvir with or without ribavirin to treat patients with HCV genotype 1 infection and cirrhosis non-responsive to previous protease-inhibitor therapy: a randomised, double-blind, phase 2 trial (SIRIUS)

The combination of ledipasvir and sofosbuvir (± ribavirin) was associated with high sustained virological response rates (96-97%) in patients with HCV genotype 1 and compensated cirrhosis who had not responded to previous treatment with pegIFN and protease-inhibitor regimens.

This study evaluated both a 12 week regimen of ledipasvir, sofosbuvir plus ribavirin and a 24-week regimen of ledipasvir and sofosbuvir. Both were associated with high sustained virological response rates (SVR; 96% and 97%, respectively). The authors of a related comment note that efficacy of the 12 week regimen obviates the high costs of 24 weeks of treatment in those who can tolerate ribavirin. Although the short duration of follow-up did not allow assessment of the effects of treatment on progression of liver disease and occurrence of decompensation and hepatocellular carcinoma, patients with SVR are eligible for enrolment in a registry that will provide longer-term data. 

 

Of note the study excluded patients with decompensated cirrhosis, and so did not address optimum therapy for this patient group. Two studies evaluating the efficacy and safety of ledipasvir-sofosbuvir with ribavirin in patients with recurrent HCV infection after liver transplantation (including those with decompensated cirrhosis) are however underway.