Treatment of patients with chronic hepatitis C has had limited success because of relapses and nonresponse to interferon alfa therapy (currently the only established therapeutic agent). A retrospective study was done to determine the efficacy of re-treatment with interferon and the predictors of response in patients who failed to achieve sustained response after one standard course of interferon therapy (3 million units three times a week for 24 weeks). One hundred and eleven patients (47 relapsers and 64 nonresponders), mean age 45 years, were included in the study. Eighteen relapsers and 13 nonresponders received a higher dose (5 MU), and 11 relapsers and 6 nonresponders received a longer duration (48 weeks) of interferon therapy. The remaining patients received the same regimen as the first treatment. Eighty-one percent and 23% of relapsers and nonresponders, respectively, had an end-of-treatment response, and 19% and 3% of the corresponding patient groups had a sustained response to re-treatment. Two patients with breakthrough during their first treatment were the only nonresponders with sustained response after re-treatment. Sustained response was observed only in patients who received an increased dose or duration of interferon therapy. No predictor of sustained response was found. In conclusion, sustained response to re-treatment with interferon was only observed with augmentation of dose or duration of therapy in some relapsers and patients who had breakthrough. Established predictors of response to interferon in naive patients, in particular serum hepatitis C virus RNA and genotype, were not associated with sustained response to re-treatment. (HEPATOLOGY 1998;27: 1144-1148.)To date, interferon remains the only established therapeutic agent for the treatment of chronic hepatitis C. Administration of 3 MU of interferon alfa three times a week for 6 months produces a sustained response rate of less than 20%. [1][2][3][4][5][6] Various workers have attempted to re-treat with interferon patients who failed to achieve sustained response after one course of interferon treatment. Discordant results have been reported, with sustained response rates ranging from 0% to 53% in relapsers and nonresponders. 7-10 Most of these studies were of small sample size, and heterogeneous treatment regimens complicate interpretation of results. Others have tried to re-treat with ribavirin, either alone 11,12 or in combination with interferon, 13,14 with variable success. However, these were again small series and their results need to be confirmed with larger randomized trials. Iron reduction, alone 15 or in combination with interferon therapy, 16 has been attempted by others, but no sustained responses were reported in these series. In summary, the appropriate retreatment regimen for relapsers and nonresponders after one course of interferon therapy is yet to be established.It has been shown that virological factors such as viral load and genotype are predictors of sustained response to the first course of interferon treatment...