Hepatocyte proliferation in chronic hepatitis C: correlation with degree of liver disease and serum alpha-fetoprotein.
OBJECTIVE
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.
Wilfredo Canchis
P
P
Center for the Study of Hepatitis C, Weill Medical College of Cornell University, New York, NY 10021, USA.
Gonzalez
Stevan A
SA
Isabel Fiel
M
M
Chiriboga
Luis
L
Yee
Herman
H
Edlin
Brian R
BR
Jacobson
Ira M
IM
Talal
Andrew H
AH
D000328:Adult; D000375:Aging; D002455:Cell Division; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood / Q000150:complications* / Q000473:pathology*; D022781:Hepatocytes / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008107:Liver Diseases / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D012720:Severity of Illness Index; D000509:alpha-Fetoproteins / Q000032:analysis*
D000509:alpha-Fetoproteins