EFFICACY OF ALPHA-INTERFERON IN CHRONIC H EPATITIS-C PATIENTS NON RESPONDER TO A FIRST TREATMENT - A PILOT PROSPECTIVE AND RANDOMIZED TRIAL

Objectives. - The aim of this study was to evaluate the efficacy of tw o 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 bio psy-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 gro ups: group 1 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 month s. 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 i n group 2. Both groups were similar for the main clinical, biochemical , and histological variables. At the end of retreatment, 2 patients (1 4.2 %) had biochemical and virological response in group 1 and 4 in gr oup 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 sustaine d 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 pa tients 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 pe riod. This improvement was statistically significant in group 2 (5.4 /- 3.0 vs 9.2 +/- 9.5 before treatment, P < 0.02) and concerned intral obular necrosis (P < 0.05). The Metavir index did not change. The numb er of side-effects was similar in both groups. Conclusions. - These re sults suggest that histological improvement may be obtained after IFN retreatment in some patients who are non-responders to the first treat ment, despite an absence of biochemical and/or virological response.