Interferon alpha (IFN-alpha) therapy is currently the treatment of choice for chronic hepatitis C (HCV) infection, but it fails to achieve a sustained response in approximately 75% of those treated. The factors which determine whether or not an individual will respond to IFN-alpha are uncertain, although a number of potentially predictive factors have been proposed. In this study a wide range of clinical, demographic, and virological parameters were evaluated in relation to therapeutic outcome in a group of 30 Italian patients with chronic hepatitis C. All patients received 3 MU leukocyte-derived IFN-alpha three times a week for 6 months and were then followed prospectively for at least 12 months. 53% of patients responded initially, but a sustained response was observed in only 17%. Responders were found to be significantly younger than nonresponders (45.6 +/- 3.1 vs. 55.4 +/- 2.7), and less frequently cirrhotic (2/16 vs. 7/14). Sustained responders had a mean pretreatment HCV-RNA titer approximately tenfold lower than that of those who did not have a sustained response, but the difference was not statistically significant. HCV genotype was found to be significantly associated with both initial and sustained response. Patients infected with HCV-2a were more likely to respond (89%) than those who were infected with HCV-1b (37%), and they were also more likely to sustain that response (33% vs. 6%).(ABSTRACT TRUNCATED AT 250 WORDS)