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

Document Type : Original Article

Authors

1 Department of Internal Medicine, Al Azhar Faculty of Medicine

2 Department of I Tropical Medicine, Al Azhar Faculty of Medicine

3 Department of Internal Medicine, National Liver Institute-Menofia University

4 Department of Clinical Biochemistry, National Liver Institute-Menofia University

5 Department of Clinical Pathology, National Liver Institute-Menofia University

6 Department of Pathology, Al Azhar Faculty of Medicine

Abstract

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 age- and 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 M30-
antigen 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.

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