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Interferon-alpha is currently the only available treatment for HCV hepatitis. We assessed the safety and efficacy of 6 month course of interferon therapy in 18 consecutive liver transplant recipients with recurrent HCV hepatitis and report the long-term response with maintenance interferon. Median follow-up after the institution of interferon was 24 months. Complete response was defined as normalization of both aspartate and alanine aminotransferase. Complete response after 6 months of interferon was observed in 28% (5/18); an additional 33% (6/18) of the patients were late responders. Overall, 61% (11/18) of the patients had long-term sustained normal response at a median follow-up of 24 months. Long-term sustained response was observed in 73% (8/11) of the patients who continued interferon beyond 6 months vs. 43% (3/7) in those who received 6 months of interferon. Fatigue, headache and cytopenia were the most commonly observed side-effects occurring in 39%, 22% and 28% of the patients, respectively. Discontinuation of interferon, however, was not required in any of the patients. Rejection was documented in 6% (1/18) patients receiving interferon; this incidence was not higher than rejection episodes occurring >6 months post-transplant in other recipients transplanted during the same period and who did not receive interferon. Responders had a trend towards later recurrence of HCV hepatitis after transplantation. In conclusion, maintenance interferon was well tolerated and appeared to improve the long-term outcome in our patients; however, future studies should evaluate this in a controlled trial.