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Liver progenitor cell markers correlate with liver damage and predict short-term mortality in patients with alcoholic hepatitis.
MedLine Citation:
PMID:  22278680     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Alcoholic Hepatitis (AH) is a severe condition developed in patients with underlying alcoholic liver disease. Ductular reaction has been associated with chronic alcohol consumption but there is no information regarding the extent of liver progenitor cell (LPC) proliferation in AH. The aim of this study was to investigate LPC markers in AH, and its correlation with disease severity. Fifty-nine patients with clinical and histological diagnosis of AH were included in the study. LPC markers were assessed by real time PCR and immunohistochemistry. Standard logistic regression analysis and classification and regression trees (CART) analysis were used for statistical analysis. A microarray analysis showed an up-regulation of LPC markers in patients with AH. Real time PCR demonstrated that epithelial cell adhesion molecule (EpCAM), Prominin-1, and Keratin7 were significantly increased in patients with AH compared to normal livers (p≤0,01), chronic hepatitis C (p≤0,01), and HCV-induced cirrhosis (p≤0,01). Immunohistochemistry scores generated for Keratin7 and EpCAM demonstrated a good correlation with gene expression. Keratin7 gene expression correlated with liver failure as assessed by MELD score (r=0.41, p =0.006) and Maddrey's discriminant function (r=0.43, p=0.004). Moreover, Keratin7 (HR1.14, p=0.004) and Prominin-1 (HR1.14, p=0.002), but not EpCAM (HR1.16, p=0.06), were identified as independent predictors of 90-days mortality. CART analysis generated an algorithm based-on the combination of Keratin7 and EpCAM gene expression that stratified three groups of patients with high, intermediate and low short-term mortality (89%, 33% and 6% respectively; AUROC 0.73, CI 95%: 0.60-0.87). Keratin7 expression provided additional discrimination potential to ABIC score. CONCLUSION: LPC markers correlate positively with severity of liver disease and short-term mortality in AH patients. This study suggests that LPC proliferation may be an important feature of AH pathophysiology. (HEPATOLOGY 2012.).
Authors:
Pau Sancho-Bru; José Altamirano; Daniel Rodrigo-Torres; Mar Coll; Cristina Millán; Juan José Lozano; Rosa Miquel; Vicente Arroyo; Juan Caballería; Pere Ginès; Ramon Bataller
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-25
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  -     ISSN:  1527-3350     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 American Association for the Study of Liver Diseases.
Affiliation:
Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain. psancho@clinic.ub.es.
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