Document Detail


Serum markers of hepatocyte death and apoptosis are non invasive biomarkers of severe fibrosis in patients with alcoholic liver disease.
MedLine Citation:
PMID:  21445263     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Quantification of hepatocyte death is useful to evaluate the progression of alcoholic liver diseases. Our aims were to quantify and correlate the circulating levels of Cytokeratin 18 (CK18) and its caspases-generated fragment to disease severity in heavy alcoholics.
METHODOLOGY/PRINCIPAL FINDINGS: CK18 and CK18-fragment were evaluated in the serum of 143 heavy alcoholics. Serum levels of markers of hepatocyte death (CK18), apoptosis (CK18 fragment) and necrosis (CK18 -CK18 fragment) increased in patients with severe fibrosis compared to patients with mild fibrosis. These markers strongly correlated with Mallory-Denk bodies, hepatocyte ballooning, fibrosis and with hepatic TNFα and TGFβ assessed in the liver of 24 patients. Elevated levels of serum hepatocyte death and apoptotic markers were independent risk factors in predicting severe fibrosis in a model combining alkaline phosphatase, bilirubin, prothrombin index, hyaluronate, hepatocyte death and apoptotic markers. The level of markers of hepatocyte death and apoptosis had an area under the receiving operator curve that predicted severe fibrosis of 0.84 and 0.76, respectively.
CONCLUSION/SIGNIFICANCE: Death of hepatocytes can be easily evaluated with serum markers and correlated with severe fibrosis in heavy alcohol drinkers. These biomarkers could be useful to rapidly evaluate liver injuries and the efficacy of therapies.
Authors:
Vanessa Jeannette Lavallard; Stéphanie Bonnafous; Stéphanie Patouraux; Marie-Christine Saint-Paul; Déborah Rousseau; Rodolphe Anty; Yannick Le Marchand-Brustel; Albert Tran; Philippe Gual
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-03-18
Journal Detail:
Title:  PloS one     Volume:  6     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2011  
Date Detail:
Created Date:  2011-03-29     Completed Date:  2011-08-02     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e17599     Citation Subset:  IM    
Affiliation:
Team 8, Hepatic complications of obesity, INSERM, U895, Nice, France.
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MeSH Terms
Descriptor/Qualifier:
Adult
Apoptosis*
Biological Markers / blood*
Female
Hepatocytes / pathology*
Humans
Liver Cirrhosis / blood*,  pathology
Liver Diseases, Alcoholic / blood*,  pathology
Male
Middle Aged
Polymerase Chain Reaction
Transforming Growth Factor beta / blood
Tumor Necrosis Factor-alpha / blood
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Transforming Growth Factor beta; 0/Tumor Necrosis Factor-alpha
Comments/Corrections

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