Sofosbuvir-Based DAA Regimens Effective for Achieving 12-Week SVR in Chronic HCV

In a study of chronic hepatitis C virus patients with compensated liver cirrhosis, sofosbuvir, a direct-acting antiviral (DAA) nucleotide analog inhibitor of the viral NS5B protein, was effective for achieving a sustained virologic response (SVR) in the majority of patients in a community care setting. The study was led by researcher Vijay Gayam, MD, of the Interfaith Medical Center in Brooklyn, New York.

“Successful treatment of chronic [hepatitis C virus infection], also described as a sustained virological response (SVR), is defined as an absence of detectable hepatitis C virus RNA 12 weeks after the completion of treatment. [Chronic hepatitis C] patients who achieve SVR have both lower rates of complications and lower overall mortality,” the investigators wrote. “Until recently, chronic [hepatitis C virus] treatment was primarily based on interferon-based regimens, but disappointing response rates, particularly amongst patients with advanced liver disease, necessitated the need for a new regimen.”

A total of 112 patients with chronic hepatitis C virus and compensated liver cirrhosis who received 12 weeks or more of combination hepatitis C virus treatment in a community clinic were included in the retrospective analysis. Combination regimens included either 90 mg/day of ledipasvir (LDV) plus 400 mg/day of sofosbuvir (SOF) ± 1000 mg/day (for <75 kg) (n = 87) or 1200 mg/day (for ≥75 kg) ribavirin (RBV) or 400 mg/day SOF plus 100 mg/day velpatasvir (VEL) (n = 25). Treatment durations were either 12 weeks (n = 98) or 24 weeks (n = 14).

The investigators assessed the safety and tolerability of therapies by retrospectively reviewing adverse events, treatment completion, dosage reductions, and medication discontinuation. Additionally, they compared pre- and post-treatment patient characteristics as well as treatment efficacy and 12-week SVR (SVR12). An undetectable viral load at 12-week follow-up comprised the SVR12. Response to therapy was evaluated using HCV RNA viral load (IU/mL) at 4-week intervals, following treatment completion, and 12 weeks after treatment.

On average, approximately 90% of patients who were treated with the DAA combination regimens achieved SVR12. In the LDV/SOF arm, 89.7% achieved SVR12, whereas 92% of patients in the SOF/VEL group achieved SVR12.

Although the univariate analysis found that higher mean body mass index, higher Child-Pugh score, low mean platelet count, low mean albumin, and low mean bilirubin levels were associated with a greater likelihood of achieving SVR12, low platelet count was the only significant predictor of therapy response in the adjusted multivariable logistic regression analysis (P = .020).

Common adverse events included fatigue (33%) and thrombocytopenia (7%), with headache (7%) and rash (8%) reported only in the LDV/SOF combination group.

“We noted an excellent [SVR] rate in patients with compensated cirrhosis irrespective of genotypes in both treatment groups, and these results are consistent with the landmark literature described above,” the authors concluded. “Our study is distinct from most studies in current literature as it establishes real-world effectiveness, tolerability, and safety of sofosbuvir-based regimens in [chronic hepatitis C] patients with compensated cirrhosis.”

The relatively small sample size, lack of randomization, and the retrospective nature of the analysis represent primary limitations of the study. To determine the true clinical applicability of the findings, randomized, placebo-controlled trials are warranted.

The study, “Sofosbuvir Based Regimens in the Treatment of Chronic Hepatitis C with Compensated Liver Cirrhosis in Community Care Setting,” was published in the International Journal of Hepatology.