Prospective comparison of four lymphoblastoid interferon alpha schedules for chronic hepatitis C. A multivariate analysis of factors predictive of sustained response to treatment.

Objective: Interferon alpha (IFN-alpha) provides effective treatment in some patients with chronic hepatitis C. Since this drug is costly and causes potentially severe side effects, there is a need for clarification of the optimal dose regimen and treatment duration and of the predictive factors of long-term response to this therapy.

Design: Prospective, randomized study in patients with chronic hepatitis C.

Setting: 'Crespi' Division of Medicine and Centre for Liver Diseases, Niguarda Hospital, Milan, Italy.

Patients And Methods: One hundred and forty-two patients with chronic hepatitis C were randomized to receive IFN-alpha at a dosage of 2-4 mega units/square metre of body surface area thrice weekly for 6-12 months. Eleven baseline variables that might predict sustained response to IFN-alpha were evaluated in this series. Sustained response was defined as normalization of transaminase levels observed by the fourth month of therapy and lasting for at least 6 months after treatment withdrawal.

Results: According to univariate analysis, variables significantly associated with sustained response to treatment were: hepatitis C virus (HCV) genotype, treatment duration, serum HCV-RNA level and duration of hepatitis. On multivariate analysis only two of these variables were found to be independently associated with sustained response to IFN-alpha: HCV genotype (P < 0.0001) and treatment duration (P = 0.0015). In the patients infected with genotype 1b, IFN-alpha was effective only when administered at the higher dosage and for the longer period.

Conclusion: Viral genotype and treatment duration are independently related to sustained response to IFN-alpha in patients with chronic hepatitis C. The patients infected with HCV genotype 1b should receive IFN-alpha at the higher dosage and for the longer period.