4.2 Article

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

Journal

ALCOHOL
Volume 41, Issue 4, Pages 271-280

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.alcohol.2007.04.008

Keywords

alcohol; STAT3; liver regeneration; cirrhosis; HCV; cell proliferation

Funding

  1. Intramural NIH HHS [Z01 AA000369-06] Funding Source: Medline
  2. NIDDK NIH HHS [N01-DK-9-2310] Funding Source: Medline

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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. (C) 2007 Elsevier Inc. All rights reserved.

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