Significance of hepatocellular proliferation in the development of hepatocellular carcinoma from anti-hepatitis C virus-positive cirrhotic patients

Background. There is a hypothesis explaining the pathogenesis of carcinoma that increased proliferation of tissue cells correlates with the development of carcinoma, presumably by increased rate of random muta-tions and by promotion. In this study, the significance of hepatocellular proliferation in the development of human hepatocellular carcinoma (HCC) from anti-hepatitis C virus (HCV)-positive cirrhotic patients was studied. Method. Twenty-eight Child A cirrhotic patients who were anti-HCV (C-100 antibody) positive were studied. At the beginning of the study, the in vitro uptake of bromodeoxyuridine (BrdU, a thymidine analogue) by he-patocytes in biopsied liver specimens was investigated as labeling indices (LIs), and they were divided into high-DNA synthetic (BrdU LI 2 1.5%) and low-DNA synthetic (BrdU LI < 1.5%) groups. The patients were then surveyed prospectively with frequent ultrasonography (every 3 months) for the development of HCC for 3 years. Result. The mean BrdU LI plus or minus standard deviation for 14 cirrhotic patients with high-DNA synthesis activity (BrdU LI 2 1.5%) was 2.7 kO.8%, and this was significantly (P < 0.001) higher than that for 14 cirrhotic patients with low-DNA synthesis activity (BrdU LI < 1.5%, 0.5 k 0.3%). Nine of 14 (64.3%) of the cirrhotic patients with high-DNA synthesis activity developed HCC in the 3-year period, in contrast to only 2 of 14 (14.3%) of the cirrhotic patients with low-DNA synthesis activity (P < 0.05). Conclusions. Proliferation of hepatocytes is important in HCC development from anti-HCV-positive cir-rhotic patients.