title: Elevated serum levels of caspase-cleaved cytokeratin 18 (CK18-Asp396) in patients with nonalcoholic steatohepatitis and chronic hepatitis C.
abstract: BACKGROUND
  Caspase-cleaved cytokeratin 18 (CK18-Asp396) is released from hepatocytes during apoptosis. Recent studies have indicated that serum levels of CK18-Asp396 could be a clinically useful biomarker of chronic liver disease. To shed more light on the rate of hepatocyte loss by apoptosis in chronic liver disease, serum levels of CK18-Asp396 were examined in patients with nonalcoholic steatohepatitis (NASH) and chronic hepatitis C.
  
  
  METHODS
  Apoptotic CK18-Asp396 levels were quantified in sera from 35 patients with nonalcoholic steatohepatitis (NASH), 21 patients with chronic hepatitis C (HCV), and 18 healthy controls.
  
  
  RESULTS
  Analysis of serum CK18-Asp396 levels showed an increasing trend starting from healthy controls (median: 54.5 U/l), to HCV patients (80.1 U/l), to patients with NASH (144.1 U/l, Kruskall-Wallis test: P<0.001). Post hoc analyses revealed that CK18-Asp396 levels were significantly higher in the NASH patients than in both HCV patients (P=0.008) and healthy controls (P<0.001). Moreover, the levels were significantly higher in patients with HCV than in control individuals (P<0.05). In patients with chronic HCV infection there was a significant positive correlation between serum CK18-Asp396 levels and AST (r=0.442, P<0.05), the ultrasonographic grade of steatosis (r=0.446, P<0.05), and the histological steatosis score (r=0.759, P<0.001).
  
  
  CONCLUSIONS
  Although subject to future confirmation, these pilot findings seem to indicate that serum levels of caspase-cleaved cytokeratin 18 (CK18-Asp396) are higher in patients with NASH than in those with chronic HCV infection. These data suggest that NASH patients have an increased hepatocyte loss by apoptosis compared with chronic hepatitis C patients.
authors.affiliation: Department of Internal Medicine, Uludag University Medical School, Bursa, Turkey. yusufyilmaz@uludag.edu.tr
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Yilmaz
authors.forename: Enver
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authors.lastname: Dolar
authors.forename: Engin
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authors.lastname: Ulukaya
authors.forename: Semra
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authors.lastname: Akgoz
authors.forename: Murat
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authors.lastname: Keskin
authors.forename: Murat
authors.initials: M
authors.lastname: Kiyici
authors.forename: Omer
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authors.lastname: Yerci
authors.forename: Arzu Yilmaztepe
authors.initials: AY
authors.lastname: Oral
authors.forename: Cuma Bulent
authors.initials: CB
authors.lastname: Gul
authors.forename: Selim
authors.initials: S
authors.lastname: Gurel
authors.forename: Selim Giray
authors.initials: SG
authors.lastname: Nak
authors.forename: Macit
authors.initials: M
authors.lastname: Gulten