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


  • This work was supported in part by The Starr Foundation for Biomedical Research and The Rita J. and Stanley H. Kaplan Comprehensive Cancer Center, National Institutes of Health Grant DK 02573, funded in part from the Speakers' Fund for Public Health Research, awarded by the City of New York.

Andrew H. Talal, MD, Center for the Study of Hepatitis C, Weill Medical College of Cornell University, 525 East 68th Street, Suite A-354, New York, NY 10021, USA.
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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.