Apoptotic Shards of Cytokeratin 18 Point to Steatohepatitis in Patients with non-Alcoholic Hepatic Steatosis,HALA I.M. HUSSIEN, HEBA F. PASHA and NAGLAA A. MOSTAFA
Abstract
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 pa-rameters 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.