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 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.

Material/Methods: Apoptotic CK18-Asp396 levels were quantified in sera from 35 patients with nonalcoholic steato-hepatitis (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: 34.5 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 and increased hepatocyte loss by apoptosis compared with chronic hepatitis C patients.