Viral and host factors in the prediction of response to interferon-alpha therapy in chronic hepatitis C after long-term follow-up

Acute infection with hepatitis C virus (HCV) develops into a chronic hepati tis in about 50-70% of patients. Treatment of these patients with interfero n-alpha (IFN-alpha) results in a sustained long-term response in only 15-20 % but causes numerous unwanted side-effects in a higher percentage of patie nts. The aim of our study was to define host or viral parameters that would allow identification of responders and non-responders to IFN-alpha prior t o the onset of treatment. We studied a group of 87 patients suffering from chronic hepatitis C who were treated with IFN-alpha. After long-term follow -up, 18: patients (21%) showed a sustained response to IFN-alpha therapy (n ormalization of serum transaminases and loss of viral RNA from serum) for u p to 7 years after therapy had ceased. By univariate and multivariate analy ses, no; host factors were found to be predictive of response to. therapy. Neither the degree of inflammation or fibrosis in liver biopsy samples obta ined before treatment nor immunogenetic factors (major histocompatibility c omplex II haplotype and tumour necrosis factor-alpha promoter polymorphism) were associated with response to therapy. In contrast, viral parameters sh owed a strong association with response to therapy. HCV genotype 3 was foun d significantly more frequently in responders (P = 0.034), and mean HCV RNA concentration was lower in responders (3.1 x 10(4)) than in non-responders (2.5 x 10(5)) (P = 0.01). By multivariate analysis, both HCV genotype and HCV RNA concentration were independent predictors of response to therapy. H owever, exact prediction of response to treatment for an individual patient was not possible on the basis of pretreatment viral RNA concentration or v iral genotype. The best association with response to therapy was found to b e clearance of HCV RNA from serum 3 months after the start of treatment (32 of 34 partial and sustained responders vs 0 of 53 non-responders; P = 0.00 1). In conclusion, determination of pretreatment; viral factors, but not ho st factors, was significantly correlated with treatment response but did no t give an accurate prediction for patients, whereas clearance of HCV RNA fr om serum after 3 months of therapy was predictive of response to therapy.