Apoptotic Shards of Cytokeratin 18 Point to Steatohepatitis in Patients with non Alcoholic Hepatic Steatosis

Background: Non-alcoholic fatty liver disease may exhibit a benign nature or sometimes progress to more aggressive steatohepatitis or even liver cirrhosis, hepatocyte apoptosis may play a role in this progression, caspase-dependent cleavage of cytokeratin (CK)18 generates a new antigen (M 30) which could be detected in patients sera. Aim of the Study: Evaluation of serum caspase-generated shards of CK 18 (M30 antigen) as a non invasive biomarker to distinguish steatohepatitis from simple hepatic steatosis in patients with non-alcoholic fatty liver disease. Subjects and Methods: The present study was conducted on 11 patients with non-alcoholic steatohepatitis and 8 patients with simple non-alcoholic hepatic steatosis who were diag-nosed histo-pathologically. In addition to 10 healthy controls. All individuals underwent liver ultrasonograhpy and laboratory investigations including assessment of lipid profile and parameters of insulin resistance. We excluded causes of chronic liver diseases rather than non-alcoholic fatty liver disease. Serum levels of CK18 fragments (M30 antigen ) were measured in patients and controls using enzyme linked immunosorbent assay. Results: Serum levels of M30 antigen in patients with non-alcoholic steatohepatitis were significantly higher than those in patients with simple non-alcoholic hepatic steatosis and controls (p 0.001). The receiver operating characteristic curve showed that, area under the curve (AUC) was=0.88 (95% CI; 0.762-1.006). At a cutoff value 124 (U/L), the sensitivity was 72.7% while the specificity was 88.9%. There were significant positive correlations between serum levels of M30 antigen and parameters of insulin resistance, degree of inflammatoin and stage of fibrosis. Conclusions: Apoptotic marker (M30 antigen) could distinguish steatohepatitis from simple hepatic steatosis in patients with nonalcoholic fatty liver disease and correlated to the degree of hepatic fibrosis.