Treatment of chronic hepatitis C with interferon alpha: long-term follow-up and prognostic relevance of HCV genotypes.

To evaluate the importance of hepatitis C virus (HCV) genotypes for the long-term response to interferon alpha (IFN alpha) therapy, we retrospectively investigated 81 patients with chronic hepatitis C treated within two randomized multicenter studies with comparable inclusion criteria. Forty patients received recombinant IFN alpha 3 MU three times a week for 12 months and 41 patients lymphoblastoid IFN alpha 3 or 5 MU three times a week for 6 or 12 months (total dosage 216-720 MU). The patients were followed up for up to 4 yr (2-4 yr, mean 3.2 yr). A sustained remission defined as normalization of aminotransferases and negative PCR for HCV-RNA was achieved in 23% of patients treated with recombinant IFN alpha and in 25% of the group with lymphoblastoid IFN alpha therapy. All patients with sustained remission showed a normalization of aminotransferases during the first 3 months of therapy. Determination of HCV genotypes revealed a major prevalence of type 1 (77%) versus type 2 (5%) and type 3 (18%). The response rate was significantly higher in patients with type 2 and 3 infections (75 and 73%) than in patients infected with genotype 1 (37%) (p = 0.005). Sustained remission was observed in 13% for genotype 1, in 75% for genotype 2, and in 33% for genotype 3 (differences between type 2/3 versus type 1, p = 0.03). There were no significant differences between responders and non-responders concerning age, level of aminotransferases before therapy or the dosage and type of IFN alpha administered. The data indicate that the determination of HCV genotypes may have prognostic relevance in the responsiveness to IFN alpha therapy.