Abstract Background/Aims: Liver stellate cell proliferation and differentiation into myofibroblast-like cells is related to the development of liver fibrosis. Several cytokines, including interferons, regulate liver stellate cell proliferation and phenotypic modulation. Recent studies indicate that human liver stellate cells express the α-isotype of actin, specific to smooth muscle cell differentiation. We aimed to evaluate the expression of α-smooth muscle actin-positive liver stellate cells in patients with chronic viral hepatitis and to evaluate whether and how such expression can be modified by α-interferon treatment. Methods: Using immunohistochemistry and a semi-quantitative scoring method, we evaluated α-smooth muscle actin expression in liver stellate cells before and after α-interferon therapy in a series of liver biopsies from 44 patients with chronic viral hepatitis Results: Before therapy, a large number of liver stellate cells expressing α-smooth muscle actin were present throughout all acinar zones. A significant reduction in α-smooth muscle actin expression by liver stellate cells was demonstrated in biopsies performed after suspending the interferon treatment. The drop in the number of α-smooth muscle actin-labelled cells after therapy correlated closely with the improvement in the histological index of activity. Conclusions: The results suggest a specific effect of interferon on liver stellate cells, possibly related to its anti-inflammatory action.