title: Serum markers of hepatocyte death and apoptosis are non invasive biomarkers of severe fibrosis in patients with alcoholic liver disease.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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: Team 8, Hepatic complications of obesity, INSERM, U895, Nice, France.
authors: Vanessa Jeannette
authors: VJ
authors: Lavallard
authors: Stéphanie
authors: S
authors: Bonnafous
authors: Stéphanie
authors: S
authors: Patouraux
authors: Marie-Christine
authors: MC
authors: Saint-Paul
authors: Déborah
authors: D
authors: Rousseau
authors: Rodolphe
authors: R
authors: Anty
authors: Yannick
authors: Y
authors: Le Marchand-Brustel
authors: Albert
authors: A
authors: Tran
authors: Philippe
authors: P
authors: Gual
mesh_terms: D000328:Adult; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood*; D005260:Female; D022781:Hepatocytes / Q000473:pathology*; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000097:blood* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha