Quantitative analysis of liver fibrosis and stellate cell changes in patients with chronic hepatitis C after interferon therapy

Objective: The proliferation and differentiation of stellate (Ito, or fat-s toring) cells into myofibroblast-like cells is responsible for the developm ent of liver fibrosis, Using computer image analysis, we evaluated the chan ges of a smooth muscle actin-positive stellate cells and liver fibrosis aft er interferon-alpha or -beta (IFN-alpha, beta) therapy in patients with chr onic hepatitis C. Methods: Patients with chronic hepatitis C were treated w ith IFN-alpha or -beta and were divided into three groups on the basis of c linical criteria; a complete responder group (CR, 18 of 51), a partial resp onder group (PR, 17 to 51), and a nonresponder group (NR, 16 of 51), Liver fibrosis was assessed from specimens stained with Sirius red and was quanti tated by computer image analysis, We also evaluated alpha-smooth muscle act in expression in the liver before and after IFN therapy by a semiquantitati ve scoring method (the alpha-smooth muscle actin index), Results: Before IF N therapy, a large number of stellate cells expressing alpha-smooth muscle actin were present in the liver biopsy specimens, There was a significant c orrelation (r = 0.699, p < 0.05) between the change in the percent area of fibrosis and the alpha-smooth muscle actin index before and after IFN thera py in all groups, The complete responder group also showed a significant re duction of alpha-smooth muscle actin-expressing cells that was correlated w ith the reduction of serum ALT (r = 0.686, p < 0.05). Conclusion: These res ults suggest alpha-smooth muscle actin-expressing cells are responsible for liver fibrosis, and the elimination of factors stimulating matrix synthesi s (e.g., hepatitis virus) may decrease liver fibrosis. (Am J Gastroenterol 1999;94:489-496. (C) 1999 by Am. Coll. of Gastroenterology).