Soluble forms of extracellular cytokeratin 18 may differentiate simple steatosis from nonalcoholic steatohepatitis

World J Gastroenterol. 2007 Feb 14;13(6):837-44. doi: 10.3748/wjg.v13.i6.837.

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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Diagnosis, Differential
  • Fatty Liver / blood*
  • Fatty Liver / diagnosis*
  • Female
  • Hepatitis / blood*
  • Hepatitis / diagnosis*
  • Humans
  • Keratin-18 / blood*
  • Liver / diagnostic imaging
  • Liver / pathology
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / diagnosis
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Predictive Value of Tests
  • Sensitivity and Specificity
  • Transaminases / blood
  • Ultrasonography

Substances

  • Biomarkers
  • Keratin-18
  • Transaminases