Elevated serum levels of caspase-cleaved cytokeratin 18 (CK18-Asp396) in patients with nonalcoholic steatohepatitis and chronic hepatitis C
Yusuf Yilmaz, Enver Dolar, Engin Ulukaya, Semra Akgoz, Murat Keskin, Murat Kiyici, Omer Yerci, Arzu Yilmaztepe Oral, Cuma Bulent Gul, Selim Gurel, Selim Giray Nak, Macit Gulten
Med Sci Monit 2009; 15(4): CR189-193
Available online: 2009-03-30
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.
Material and Method: 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.
Keywords: Keratin-18 - blood, Hydrolysis, Hepatitis C, Chronic - blood, Fatty Liver - blood, Enzyme-Linked Immunosorbent Assay, Caspases - metabolism, Adult, Adolescent, young adult