Maintenance therapy with gradual reduction of the interferon dose over one year improves histological response in patients with chronic hepatitis C with biochemical response: results of a randomized trial.

BACKGROUND/AIMS: Our aim was to assess whether histological response was improved by continuing interferon-alpha (IFN) treatment in patients with chronic hepatitis C (HCV) with a biochemical response and no viral clearance after a usual IFN treatment. METHODS: Fifty-seven patients with normal alanine aminotransferase (ALAT) levels and positive HCV RNA at the end of a 1 year IFN treatment were randomly assigned to either group 1 (n = 28) where IFN was stopped, or group 2 (n = 29) where IFN was continued for 1 more year with gradual reduction of the dose to keep serum ALAT activity below the upper limit of normal. Liver biopsies were obtained before, and then 6 months after the end of treatment. RESULTS: Knodell's index improved between paired biopsies in group 2 (8.2+/-2.4 vs. 5.5+/-2.1), but not in group 1 (8+/-2.3 vs. 6.5+/-2). In post-treatment biopsies, the METAVIR activity score was significantly lower in group 2 than in group 1 (0.7+/-0.2 vs. 1.1+/-0.3, P < 0.05). In group 2, an improvement of the METAVIR fibrosis score was observed (1.3+/-0.4 vs. 1.1+/-0.2), whereas fibrosis progressed in group 1 (1.3+/-0.4 vs. 1.6+/-0.4). CONCLUSIONS: Maintenance therapy by the minimal dose of IFN able to maintain biochemical response prevents histological progression in the sub-group of patients without virological response.

Study of host- and virus-related factors associated with spontaneous hepatitis C virus clearance.

Epidemiologic parameters, virologic characteristics and frequency of HLA class II DR and DQ antigens were compared between 63 subjects with spontaneous hepatitis C virus clearance (group 1) and 282 patients with chronic active hepatitis C virus infection (group 2). DRB1*1101 and moreover DQB1*0301 alleles were more frequent in group 1 than in group 2 (33.8% vs. 14.7% and 64.4% vs. 28.6%; P=0.012 and P=0.003, respectively). The frequency of DQB1*02 was lower in group 1 than in group 2 (25.4% vs. 49%; P=0.04). No difference was observed in viral genotype distribution between group 1 and group 2. Univariate analysis showed that female sex and contamination by intravenous drug use were associated with self limited infection. However, by multivariate analysis, the only independent factor associated with hepatitis C virus RNA clearance was female sex (P=0.004). In conclusion, spontaneous hepatitis C virus RNA clearance is determined by class II antigens (mainly DQB1*0301) and female sex, while viral genotype plays no role.