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Non alcoholic steatohepatitis (NASH) could be present in one third of non alcoholic fatty liver disease (NAFLD) cases and appears to have a higher likelihood of progression to cirrhosis. An increased risk of hepatocellular carcinoma and endstage liver disease has been reported among patients with NASH. However, liver biopsy is an invasive procedure with unavoidable risks and limitations and it is not relevant to the choice of treatment. Therefore, the development of non invasive tests for assessing hepatic inflammation and fibrosis has become an active area of research. The present study aimed to investigate whether serum levels of two soluble forms of extracellular cytokeratin 18 (M30-antigen and M65-antigen) may differentiate NASH from simple fatty liver in patients with NAFLD. Fifty eight patients with suspected NAFLD were classified according to their liver histology into two groups (27 of NASH and 31 of simple steatosis), and 25 healthy ageand gendermatched volunteers were enrolled in the study. Clinical examination, anthropometric measurements, abdominal ultrasound and liver biopsy were done to all patients. Laboratory investigations which included lipid profile, liver function tests and fasting insulin level were done. Serum levels of two soluble forms of extracellular cytokeratin 18 (M30-antigen and M65-antigen) were measured. Serum levels of M30-antigen and M65-antigen were significantly higher in patients with definitive NASH compared to the group of simple steatosis and control group. At cut-off value >114.7 U/L of M30antigen yielded an 81.5% sensitivity and a 93.5% specificity and M65-antigen at the cut-off level >254.5 U/L gave a sensitivity of 70.4% and specificity of 77.5% for the diagnosis of NASH. The level of each M30 and M65 antigens correlated positively with AST & ALT activities and histological features of NAFLD patients. In conclusion: these findings suggest that determination of CK-18 fragments in the blood could be used as a non invasive predictor of NASH and highlight the potential usefulness of that test as a noninvasive diagnostic means of determining histological disease severity in patients with NAFLD. Bull. Egypt. Soc. Physiol. Sci. 31 (2) 2011 Ali et al.

The Clinical Value of Soluble Cytokeratin-18 in Differentiating Simple Steatosis from Non Alcoholic Steatohepatitis