Background: Antiviral therapy has not been adequately evaluated in patients with hepatitis C virus (HCV)-related advanced liver disease due to apprehensions of adverse events and intolerance. The titrable dose of interferon (IFN)-alpha and ribavirin was evaluated in a flexible regimen in a pilot study.
Methods: Twenty-five patients with HCV-related advanced chronic liver disease received IFN-alpha 1-3 MIU daily with ribavirin 200-600 mg daily for 9 months-3 years. Careful assessment of safety, tolerability and efficacy was made.
Results: Improvement in Child-Pugh score (8.4 +/- 1.2 to 7.4 +/- 2.0; P = 0.010) and serum albumin (3.0 +/- 0.5 g/dL to 3.6 +/- 0.5 g/dL; P = 0.007) occurred at follow up after antiviral therapy (median dose and duration: IFN-alpha 1.5 MIU/day for 12 months and ribavirin 400 mg/day for 7.5 months) as compared to baseline. Ascites regressed in 53% of patients (11/21). Thirteen patients (52%) lost HCV-RNA on therapy and eight (32%) achieved sustained virological response (SVR). Death occurred in three patients (12%) while on therapy, in two due to infection. No patient died in the responder group compared to five deaths (29%) in the non-responder group. However, there was no difference in the cumulative probability of survival in the sustained virological responder versus non-responder (P = 0.09). Adverse events were common (92%), but permanent withdrawal was required in only five patients (20%).
Conclusions: Low and titrable dose IFN-alpha and ribavirin therapy in patients with HCV-related advanced chronic liver disease achieves improvement in hepatic synthetic function, Child-Pugh score and ascites. However, close monitoring for serious adverse events is warranted.