[Value of high-dose interferon-alpha in chronic viral hepatitis C patients non-responder to a 1st treatment. Pilot study prospective and randomized trial]

Abstract

Objectives: The aim of this study was to evaluate the efficacy of two different doses of alpha interferon (IFN) for retreatment in chronic hepatitis C patients who were non responders to initial treatment by IFN at a dose of 3 MIU TIW for 6 months.

Methods: This open, pilot, prospective, randomized and bicentric study included patients with biopsy-proven chronic hepatitis C. Non response was defined as serum ALT levels > 2 upper limit of normal for the entire first treatment period, HCV RNA positivity by PCR at the end of the first treatment period, and the persistence of histologically-proven chronic active hepatitis after the first treatment period. Patients were randomized into two groups: group I received IFN alpha 2b 10 MIU TIW for 2 months, then 6 MIU TIW for 4 months, group 2 received IFN alpha 2b 6 MIU TIW for 6 months.

Results: Twenty three patients (17 male, 6 female, mean age: 38.7 +/- 9.1 years) were included: 14 were randomized in group 1 and 9 in group 2. Both groups were similar for the main clinical, biochemical, and histological variables. At the end of retreatment, 2 patients (14.2%) had biochemical and virological response in group 1 and 4 in group 2 (44.4%) (non significant). Only one biochemical and virological sustained response was observed in group 2 (11.1%) (non significant). There was no difference between the groups for complete and sustained response. An overall statistical significant improvement of Knodell score was observed (7.8 +/- 3.8 vs 9.6 +/- 3.2, P < 0.02) in the 18 patients who had a second biopsy 6 months after the end of therapy, while the Knodell score did not change at the end of the first treatment period. This improvement was statistically significant in group 2 (5.4 +/- 3.0 vs 9.2 +/- 9.5 before treatment, P < 0.02) and concerned intralobular necrosis (P < 0.05). The Metavir index did not change. The number of side-effects was similar in both groups.

Conclusions: These results suggest that histological improvement may be obtained after IFN retreatment in some patients who are non-responders to the first treatment, despite an absence of biochemical and/or virological response.