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In chronic hepatitis C (HCV) infection, treatment with interferon is associated with a rather low rate of sustained response and many treated patients do not achieve significant benefit. Efforts have therefore been made to identify non-responders as early as possible to avoid unjustified costs and side-effects. We treated 106 cases of HCV with an algorithm based on the results of sequential alanine aminotransferase (ALT) and HCV RNA determinations, using an initial dose of 6 MU thrice weekly for 4 months, and modified the subsequent treatment according to the biochemical and virological profile. Thirty-three out of 48 patients (68.7%) who were HCV RNA negative with normal ALT at 4 months after initiation of treatment were sustained responders when treated for an additional 4-month period with a reduced 3 MU dose, while sustained response was achieved in 12.5% of HCV RNA positive patients treated with a higher dosage and for a more prolonged period of time. Our findings indicate that HCV RNA monitoring during interferon therapy may be useful in modifying of the treatment schedule for the individual patient.