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Liver histology was compared in patients with chronic hepatitis C to clarify the difference between responders and non-responders to interferon therapy. We have treated 50 patients with chronic hepatitis C by natural IFN-alpha 6.0 MU/day for 2 weeks, daily, followed by intermittent therapy for 3-6 months. The overall effect of IFN was a complete response (CR) in 16 (32%), transient response (TR) in 14 (28%), and no response (NR) in 20 (40%). According to the pre-treatment liver histology, CR had a lower total numerical scores than TR and NR. Histological difference between CR and TR appeared to be the degree of portal inflammation and piecemeal necrosis, though NR showed an increase in portal fibrosis compared of CR and also TR. Response to IFN may depend on the degree of liver fibrosis rather than other histological factors. To assess the degree of liver fibrosis is thought to be important for the prediction of the efficacy of IFN therapy.