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Background: Interaction between Fas antigen on hepatocytes and Fas ligand on cytotoxic T cells induces apoptosis, a major mechanism of hepatitis C virus (HCV)-induced hepatocyte injury. We investigated the usefulness of Fas expression on hepatocytes as a predictor of short- and long-term response to interferon (IFN) therapy in 72 patients with chronic hepatitis C. Methods: Ten million units of recombinant IFN-α2b were administered daily for the first 2 weeks, and three times a week for another 22 weeks. The short-term efficacy of IFN therapy was evaluated after 12-month follow-up from cessation of treatment. We also examined the long-term response to IFN at 56.6 ± 10.8 (mean ± s) months after termination of IFN therapy in 55 of 72 patients. Results: Univariate analysis showed that serum HCV-RNA levels, HCV genotype and Fas expression significantly correlated with the short-term efficacy of IFN therapy (P = 0.005, 0.006, and 0.04, respectively). Fas antigen expression did not correlate with serum HCV-RNA levels (P = 0.286), but significantly correlated with HCV genotype (P = 0.003). Multivariate analysis indicated that Fas expression and serum HCV-RNA levels were independent determinants of the shortterm response to IFN therapy. Combined together, Fas expression and serum HCV-RNA levels accurately predicted the short-term response to IFN therapy. On the other hand, in 55 patients who were examined the long-term response to IFN, about 60% of Fas-positive patients were HCV-RNA negative, whereas 30% of Fas-negative patients were HCV-RNA negative (P = 0.04). Among Fas-positive patients, the percentage of those with serum ALT levels persistently lower than twice the normal upper limit in long-term study (81.8%; 9/11) was significantly higher than those in short-term study even among patients who failed to show elimination of HCV-RNA (36.4%; 4/11, P = 0.03). Conclusion: Our results indicate that Fas expression on hepatocytes is a good predictor of the short-and long-term response to IFN therapy. [ABSTRACT FROM AUTHOR]