Efficacy and Safety of Sofosbuvir-based Regimens in Hepatitis C Patients With Decompensated Cirrhosis: A Systematic Review and Meta-analysis

Background and Aims: Decompensated cirrhotic patients with hepatitis C (HCV) are often under-represented in clinical trials. We aimed to evaluate pooled data on the efficacy and safety of sofosbuvir (SOF)-based regimens in these patients. Methods: We conducted a systemic review and meta-analysis by searching multiple databases for studies published from October 2010 to October 2020. Outcomes of interest were sustained virologic response (SVR) and safety of SOFbased regimens in decompensated HCV patients. Two reviewers independently performed the study selection and data extraction. Results: We included 33 studies that enrolled 5,302 HCV patients. The pooled SVR rate in decompensated patients with SOF-based regimens was 85.1% (95% CI: 82.8–87.3). Patients on SOF/velpatasvir±ribavirin achieved a significantly higher SVR (91.0%, 95% CI: 87.7–93.9) than that of SOF/ledipasvir±ribavirin [(86.3%, 95% CI: 84.6– 87.8); p=0.004)], or on SOF/daclatasvir±ribavirin (82.4%, 95% CI: 78.2–86.2%; p<0.001). Adding ribavirin to SOFbased regimens (pooled SVR 84.9%, 95% CI: 81.7–87.9) did not significantly increase the SVR [(83.8% (95% CI: 76.8– 89.8%; p=0.76)] in decompensated patients, which was also true in subgroup analyses for each regimen within the same treatment duration. However, adding ribavirin significantly increased the frequency of adverse events from 52.9% (95% CI: 28.0–77.1) to 89.2% (95% CI: 68.1–99.9) and frequency of severe events. The pooled incidence of hepatocellular carcinoma and case-fatality of decompensated patients were 3.1% (95% CI: 1.5–5.0) and 4.6% (95% CI: 3.1–6.3), respectively. The overall heterogeneity was high. There was no publication bias. Conclusions: The analysis found that 12 weeks of SOF/velpatasvir without ribavirin is the preferred therapy, with a significantly higher SVR compared with other SOF-based regimens in decompensated HCV patients.