HEPATOCYTE PROLIFERATIVE ACTIVITY IN CHRONIC LIVER-DAMAGE AS ASSESSEDBY THE MONOCLONAL-ANTIBODY MIB1 KI67 IN ARCHIVAL MATERIAL - THE ROLE OF ETIOLOGY, DISEASE-ACTIVITY, IRON, AND LIPID-PEROXIDATION

Hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related liver dam age is linked to an increased risk of hepatocellular carcinoma, but th e mechanisms underlying hepatitis C viral activity are not known. We t herefore compared hepatocellular proliferative activity in chronic C v irus-related hepatitis and in liver damage of other etiology, Hepatocy te proliferation rate was investigated in 56 patients with chronic hep atitis using the Ki67 MIB1 monoclonal antibody in archival material, A ccording to etiology, the patients were subgrouped as follows: HCV (34 ), HBV (11), Alcohol (4), HCV + Alcohol (4), and Hemochromatosis (3). Proliferation rate was correlated with age, sex, etiology, disease act ivity, liver iron storage, free-radical production, and glutathione le vels by regression and discriminant analysis. HCV-positive patients ha d significantly more MIB1-positive hepatocytes in the periportal area (P < .011) and in the low-proliferating perivenular area (zones 2 and 3) (P < .05). The number of MIB1-positive cells correlated directly wi th alanine transaminase (ALT) levels, Knodell index (KI), and, inverse ly, with iron saturation. By stepwise discriminant analysis, ALT level s and etiology were identified as single independent variables. These data suggest that HCV infection induces increased and abnormal hepatoc yte proliferation, which might be related to the increased risk of hep atocellular carcinoma in patients with HCV-related liver damage.