Hepatocyte proliferation in chronic hepatitis C:: correlation with degree of liver disease and serum α-fetoprotein

Aims: Hepatocyte proliferation (HP) is an adaptive response to liver injury. The relationships between HP and necroinflammation, fibrosis, and serum alpha-fetoprotein (AFP) levels in chronic hepatitis C virus (HCV) infection, however, are not well understood. Methods: Proliferative hepatocytes (Ki-67(+)) were identified using immunohistochemical staining in formalin-fixed, paraffin-embedded liver tissue from 156 HCV RNA-positive patients with different degrees of liver histopathology. Twenty high-power fields (HPFs) in lobular areas were counted in each specimen. Results: HP increased by 1.22+/-0.25 cells/HPF per increase in necroinflammation from grade 0 (median: 0.13; range: [0.1-0.5] cells/HPF) through grade 3 (median: 1.80; range: [0.0-25.2] cells/HPF; P=0.002). HP increased by 0.81 +/-0.20 cells/HPF per increase in fibrosis from stage 0 (median: 0.33; range: [0.0-1.3] cells/HPF) through stage 3 (median: 1.70; range: [0.0-25.2] cells/HPF) and then decreased in stage 4 (to median: 0.90; range: [0.0-5.3] cells/HPF). HP also increased with advancing age (P=0.03). Among patients with advanced liver disease, HP was no higher in patients with elevated serum AFP levels (median: 1.68; range: [0.1-5.3] cells/HPF) than in those with normal serum AFP levels (median: 1.70; range: [0.0-25.2] cells/HPF; P=0.26). Conclusions: In patients with chronic HCV infection, HP increases with histologic progression of liver disease, but is impaired in cirrhosis. HP was not increased in patients with elevated serum AFP levels.