High sustained response rate in patients with histologically mild (low grade and stage) chronic hepatitis C infection. A randomized, double blind, placebo controlled trial of interferon alpha-2b with and without ribavirin.

OBJECTIVE : To evaluate the efficacy and safety of therapy for patients with histologically mild hepatitis C virus (HCV) liver disease. DESIGN : A randomized, double blind, placebo controlled trial of interferon alpha-2b with or without ribavirin. SETTING : Regional and university hospitals. PARTICIPANTS : One hundred and sixteen treatment naive patients with mild chronic HCV infection. Mild HCV infection was defined according to Knodell as a grade score of >/= 1 and </= 6 and a stage score of </= 1. INTERVENTIONS : Interferon alpha-2b (3 MU three times weekly) for 52 weeks in combination with either ribavirin or a matched placebo. MAIN OUTCOME MEASURES : The study endpoint was the absence of HCV RNA in plasma and liver tissue 26 weeks post-treatment. In addition, liver histology was compared pre- and post-treatment. RESULTS : Combination therapy was superior to interferon monotherapy, with a virological sustained response rate of 54% (31/57) and 20% (12/59), respectively, in both serum and liver tissue (P = 0.001). The sustained response rate was higher with combination therapy than monotherapy both in genotype non-1 (81% vs 36%) and in genotype 1 (28% vs 4%). There was a significant improvement in mean grade score in all sustained responders, irrespective of treatment arm. CONCLUSION : Combination therapy with interferon and ribavirin was safe and as effective in patients with histologically mild HCV infection as previously reported for more advanced disease.