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 mutations 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. METHODS: 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 hepatocytes in biopsied liver specimens was investigated as labeling indices (LIs), and they were divided into high-DNA synthetic (BrdU LI > or = 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. RESULTS: The mean BrdU LI plus or minus standard deviation for 14 cirrhotic patients with high-DNA synthesis activity (BrdU LI > or = 1.5%) was 2.7 +/- 0.8%, 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 +/- 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).