Liver regeneration is suppressed in alcoholic cirrhosis: correlation with decreased STAT3 activation

Alcohol. 2007 Jun;41(4):271-80. doi: 10.1016/j.alcohol.2007.04.008.

Abstract

Liver regeneration is suppressed in alcoholic patients; however, the underlying mechanisms are not fully understood. We examined liver regeneration and signal transducer and activator of transcription 3 (STAT3) activation (an important signal for liver regeneration) in cirrhotic livers from alcoholics, hepatitis C virus (HCV) infection, and alcoholic plus HCV infection. Liver regeneration and STAT3 activation were determined by immunohistochemistry analysis of Ki67 and STAT3 phosphorylation, respectively, in 20 alcoholic cirrhosis, 13 HCV cirrhosis, 13 alcoholic+HCV cirrhosis. Alcoholic or alcoholic plus HCV cirrhotic livers had significantly lower Ki67+ and phospho-STAT3+ (pSTAT3+) hepatocytes and bile duct cells than HCV cirrhotic livers. The pSTAT3 positive staining did not correlate with liver injury (elevation of serum levels of aspartate transaminase [AST] and alkaline phosphatase [ALP]) but correlated positively with cell proliferation (Ki67 positive staining).

In conclusion: liver regeneration is suppressed in alcoholic cirrhotic livers, which may be partly due to decreased STAT3 activation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Albumins / metabolism
  • Alkaline Phosphatase / metabolism
  • Aspartate Aminotransferases / blood
  • Bile Ducts / cytology
  • Bile Ducts / drug effects
  • Bile Ducts / metabolism
  • Bilirubin / metabolism
  • Biotransformation / physiology
  • Cell Proliferation
  • Creatinine / blood
  • Female
  • Hepatocytes / physiology
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism
  • Liver Cirrhosis, Alcoholic / metabolism*
  • Liver Cirrhosis, Alcoholic / pathology*
  • Liver Regeneration / physiology*
  • Male
  • Middle Aged
  • STAT3 Transcription Factor / physiology*

Substances

  • Albumins
  • Ki-67 Antigen
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Creatinine
  • Aspartate Aminotransferases
  • Alkaline Phosphatase
  • Bilirubin