1. Sofosbuvir-velpatasvir with or without ribavirin resulted in sustained virologic response at 12 weeks across all hepatitis C virus (HCV) genotypes in patients with decompensated cirrhosis.
2. Rates of adverse events were similar across all treatment groups.
Evidence Rating Level: 1 (Excellent)
Study Rundown: HCV infection has the potential to become a chronic infection causing cirrhosis and thus decompensated liver failure. Currently one of the main management options is liver transplantation. However recent developments in antivirals have opened the doors to medical management that may lead to complete viral suppression. The NS5B nucleotide inhibitor is currently approved for HCV infection however the new velpatasvir is currently in Phase 3 clinical trials. This open-label randomized controlled trial compared sofosbuvir-velpatasvir with and without ribavirin for 12 weeks or sofosbuvir-velpatasvir for 24 weeks in patients infected with HCV genotypes 1 to 6 and decompensated cirrhosis to assess for efficacy and safety.
All three treatment regimens resulted in sustained virologic responses at 12 weeks across all HCV genotypes; meeting the prespecified primary efficacy end point set by study investigators. There was evidence for improvement in liver function as measured by Child-Pugh-Turcotte (CPT) and Model for End-Stage Liver Disease (MELD) scores. Strengths of the study include being a multicenter and randomized study looking at efficacy of these medications in the sick decompensated cirrhosis patient population. A major limitation of this study is that it was not statistically powered to detect significant differences between efficacy and adverse events across treatment groups. Also it must be cautioned extrapolating these results to very ill patients with severe liver disease as the patient population in this study had moderate hepatic decompensation.
In-Depth [randomized controlled trial]: This 1:1:1 randomized, open-label controlled trial was conducted at 47 sites across the United States. Patients had HCV infection of any genotype and CPT Class B. Both patients not treated and previously treated were included, however those who received liver transplants were excluded. Patients were randomly assigned to either sofosbuvir-velpatasvir for 12 weeks, sofosbuvir-velpatasvir plus ribavirin for 12 weeks or sofosbuvir-velpatasvir for 24 weeks (current duration for standard of care). The primary end point was sustained virologic response at 12 weeks after end of therapy. Liver function as represented by changes in CPT and MELD scores were also analyzed.
In total 438 patients were screened and underwent randomization. Demographics and baseline characteristics were generally well balanced and had representation of almost all HCV genotypes (missing genotype 5). Seventy-eight percent of patients had genotype 1. The median CPT score was 8, Class B, (range 5-10) and MELD score was 10 (range 6 to 24). Overall rates of sustained virologic response for the sofosbuvir-velpatasvir x 12 weeks, sofosbuvir-velpatasvir plus ribavirin and sofosbuvir-velpatasvir x 24 weeks were 83% (95% CI 74%-90%), 94% (95% CI 87%-98%) and 86% (95% CI 77%-92%) respectively.
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