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

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Abstract
Aims: Hepatocyte proliferation (HP) is an adaptive response to liver injury. The relationships between HP and necroinflammation, fibrosis, and serum α-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.