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


CONCLUSIONS
liver regeneration is suppressed in alcoholic cirrhotic livers, which may be partly due to decreased STAT3 activation.
Horiguchi
Norio
N
Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Rm 2S-33, Bethesda, MD 20892, USA.
Ishac
Edward J N
EJ
Gao
Bin
B
D000328:Adult; D000368:Aged; D000418:Albumins / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D001652:Bile Ducts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism; D001711:Biotransformation / Q000502:physiology; D049109:Cell Proliferation; D003404:Creatinine / Q000097:blood; D005260:Female; D022781:Hepatocytes / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism* / Q000473:pathology*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D050796:STAT3 Transcription Factor / Q000502:physiology*
D000418:Albumins; D019394:Ki-67 Antigen; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase; D001663:Bilirubin