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Glutamine synthetase expression in activated hepatocyte progenitor cells and loss of hepatocellular expression in congestion and cirrhosis.
MedLine Citation:
PMID:  23362937     Owner:  NLM     Status:  Publisher    
BACKGROUND AND AIMS: In normal human liver, glutamine synthetase (GS) is expressed in a rim of hepatocytes surrounding hepatic veins. GS expression is decreased in cirrhosis and increased in chronic hepatitis, focal nodular hyperplasia, peritumoural hyperplasia and some hepatocellular neoplasms. For the non-neoplastic conditions, there is limited information available on histological pattern of altered GS expression and the mechanisms of these changes. METHODS: We examined GS expression in 58 large specimens and 45 needle biopsies with a variety of non-neoplastic human liver conditions and in 12 normal control livers. Expression was correlated with clinical and histological disease states. RESULTS: We identified four patterns of GS expression: (i) Loss of normal perivenular expression was seen in states of chronic congestion, severe cirrhosis and zone 3 necrosis. (ii) Diffuse expression was seen in states with active hepatocellular injury and correlated with Ki-67 expression. (iii) Interface expression was seen in feathery degeneration of chronic cholestasis. (iv) GS expression in activated hepatocyte progenitor cells (HPCs) associated with small ducts and ductules was seen in fulminant hepatic failure and in early and late chronic liver disease and rarely in normal livers. CONCLUSIONS: Glutamine synthetase expression is increased in regenerating hepatocytes and in early HPCs prior to morphological evidence of hepatocellular differentiation. This may be the earliest marker of HPCs yet demonstrated. Loss of expression may be a reflection of disrupted endothelium-hepatocyte contact in hepatic vein walls caused by congestive injury as found in congestive heart failure and advanced cirrhosis.
Kirsten E Fleming; Ian R Wanless
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-3
Journal Detail:
Title:  Liver international : official journal of the International Association for the Study of the Liver     Volume:  -     ISSN:  1478-3231     ISO Abbreviation:  Liver Int.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101160857     Medline TA:  Liver Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 John Wiley & Sons A/S.
Department of Pathology, Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada.
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