Patients with chronic viral hepatitis are at high risk of developing cirrhosis, but the outcome of the disease in a given patient is unpredictable. Hepatic stellate cells have been demonstrated to be the most important cell type involved in hepatic fibrogenesis, regardless of the cause of the liver injury. The alpha isotype of actin (a phenotypic marker of smooth muscle cells) may be expressed by hepatic stellate cells, reflecting their "activation" to myofibroblast-like cells. The present study aimed to analyze the expression of alpha-smooth muscle actin-positive hepatic stellate cells in liver allografts with recurrent viral hepatitis, and to evaluate whether and how such expression may be related to the outcome of the disease. Using immunohistochemistry and a semi-quantitative scoring system, the expression of a-smooth muscle actin in hepatic stellate cells was analyzed in liver allografts of 17 patients with recurrent viral hepatitis. They included nine patients who developed cirrhosis at the end of follow-up (mean time 23.6 months), and eight patients with no cirrhosis at the end of a comparable follow-up time (mean 30.1 months). In all patients, liver biopsy specimens were obtained between 3 and 6 months (t1) and between 10 and 15 months (t2) after transplantation. Preperfusion biopsy specimens of donor livers served as a baseline (t0). By comparison with the baseline biopsy, an increased number of alpha-smooth muscle actin-expressing hepatic stellate cells was observed in all cases in t1 biopsies. An increase in the amount of alpha-smooth muscle actin-positive hepatic stellate cells in zone 1 at t1 was significantly (P < .006) related to subsequent cirrhotic evolution. In conclusion, in liver allografts with recurrent viral hepatitis, the activation of hepatic stellate cells is an early event. An increased number of alpha-smooth muscle actin-positive hepatic stellate cells in zone 1 may represent an unfavorable event related to cirrhotic evolution.