Abstract: Objective To observe the histological changes in the fibrotic and inflammatory tissues in response to interferon alpha treatment in patients with chronic viral hepatitis B. Methods Sixteen patients with chronic viral hepatitis B in S₃-S₄ stages established by pathological examination were treated with interferon alpha for 6-9 months, and the degree of liver fibrosis and inflammation were examined 3 times during the treatment. The expression of Fas, transforming growth factor β1 (TGFβ1) and HBcAg in the liver tissues were detected by immunohistochemistry, and DNA fragmentation was examined by TUNEL assay. The levels of the serum markers for liver fibrosis and liver function were also measured. Results Patients with liver fibrosis in S₃-S₄ stages had high pathological expression of Fas and TGFβ1 with severe DNA damage in the liver tissues. After 3 months of interferon therapy, the expression of Fas and TGFβ1 were lowered (P<0.05), and further treatment till 3-9 months resulted in gradual decrease in the degree of hepatic fibrosis and cell apoptosis (P<0.05), with improved serum liver fibrosis indices and liver function. Conclusion Interferon alpha may alleviate liver fibrosis and suppress cell apoptosis in patients in S₃-S₄ stages after a 6- to 9-month continuous treatment.