Abstract: Aims/Background: The purpose of the present study was to evaluate the effects of interferon-α (IFNα) treatment on necro-inflammatory changes, viral antigen expression and hepatocytic proliferation rate assessed by Ki-67 protein in liver biopsies of children with chronic hepatitis B virus (HBV) infection. Methods: The study included 18 children at prepubertal age. Histologic changes were assessed using a modified scoring system for grading of histological activity index and staging of fibrosis. The hepatocytic expression of Ki-67 and HBV antigens including HBV surface antigen (HBsAg) and HBV core antigen (HBcAg) were evaluated using a semi-quantitative immunohistochemical scoring system. Results: We found a significant decrease in the scores of intralobular confluent and spotty necrosis, periportal piecemeal necrosis, and in Ki-67 immunopositivity after treatment. Serologic response with clearance of HBV e antigen in 9 patients (50%) was associated with this improvement. The extent of fibrosis and scoring of portal inflammation, however, did not show any difference. HBcAg expression showed a significant decrease after treatment, whereas HBsAg expression either increased or remained unchanged. Conclusion: We conclude that IFNα treatment might provide an improvement in hepatic histology with a reduction in hepatocytic injury. It might also provide a serologic response associated with a decrease in hepatocytic HBV replication.