Viral Hepatitis
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World J Gastroenterol. Feb 14, 2007; 13(6): 837-844
Published online Feb 14, 2007. doi: 10.3748/wjg.v13.i6.837
Soluble forms of extracellular cytokeratin 18 may differentiate simple steatosis from nonalcoholic steatohepatitis
Yusuf Yilmaz, Enver Dolar, Engin Ulukaya, Semra Akgoz, Murat Keskin, Murat Kiyici, Sibel Aker, Arzu Yilmaztepe, Selim Gurel, Macit Gulten, Selim Giray Nak
Yusuf Yilmaz, Uludag University Medical School, Department of Internal Medicine, Bursa, Turkey
Enver Dolar, Murat Keskin, Murat Kiyici, Selim Gurel, Macit Gulten, Selim Giray Nak, Uludag University Medical School, Department of Gastroenterology, Bursa, Turkey
Engin Ulukaya, Arzu Yilmaztepe, Uludag University Medical School, Department of Biochemistry, Bursa, Turkey
Semra Akgoz, Uludag University Medical School, Department of Statistics, Bursa, Turkey
Sibel Aker, Uludag University Medical School, Department of Pathology, Bursa, Turkey
Author contributions: All authors contributed equally to the work.
Correspondence to: Yusuf Yilmaz, MD, Uludag Universitesi Tip Fakultesi Ic Hastaliklari Gorukle, Bursa 16059, Turkey. yusufyilmaz@uludag.edu.tr
Telephone: +90-533-4403995 Fax: +90-224-4434119
Received: November 17, 2006
Revised: December 1, 2006
Accepted: December 19, 2006
Published online: February 14, 2007
Abstract

AIM: To investigate whether serum levels of two soluble forms of extracellular cytokeratin 18 (M30-antigen and M65-antigen) may differentiate nonalcoholic steatohepatitis (NASH) from simple steatosis in patients with nonalcoholic fatty liver disease (NAFLD).

METHODS: A total of 83 patients with suspected NAFLD and 49 healthy volunteers were investigated. Patients with suspected NAFLD were classified according to their liver histology into four groups: definitive NASH (n = 45), borderline NASH (n = 24), simple fatty liver (n = 9), and normal tissue (n = 5). Serum levels of caspase-3 generated cytokeratin-18 fragments (M30-antigen) and total cytokeratin-18 (M65-antigen) were determined by ELISA.

RESULTS: Levels of M30-antigen and M65-antigen were significantly higher in patients with definitive NASH compared to the other groups. An abnormal value (> 121.60 IU/L) of M30-antigen yielded a 60.0% sensitivity and a 97.4% specificity for the diagnosis of NASH. Sensitivity and specificity of an abnormal M65-antigen level (> 243.82 IU/L) for the diagnosis of NASH were 68.9% and 81.6%, respectively. Among patients with NAFLD, M30-antigen and M65-antigen levels distinguished between advanced fibrosis and early-stage fibrosis with a sensitivity of 64.7% and 70.6%, and a specificity of 77.3% and 71.2%, respectively.

CONCLUSION: Serum levels of M30-antigen and M65-antigen may be of clinical usefulness to identify patients with NASH. Further studies are mandatory to better assess the role of these apoptonecrotic biomarkers in NAFLD pathophysiology.

Keywords: Steatosis; Steatohepatitis; Cytokeratin 18; M30-antigen; M65-antigen