Limited utility of plasma M30 in discriminating non-alcoholic steatohepatitis from steatosis--a comparison with routine biochemical markers

PLoS One. 2014 Sep 3;9(9):e105903. doi: 10.1371/journal.pone.0105903. eCollection 2014.

Abstract

Introduction: The utility of Cytokeratin-18 fragment, namely CK18Asp396 (M30), for the diagnosis of non-alcoholic steatohepatitis (NASH) is currently uncertain. We aimed to provide further data in this area among multi-ethnic Asian subjects with NAFLD.

Materials and methods: The accuracy of M30 for detecting NASH was compared with serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transpeptidase (GGT) levels in consecutive adult subjects with biopsy-proven non-alcoholic fatty liver disease (NAFLD).

Results: Data for 93 NAFLD subjects (mean age 51.0 ± 11.1 years old and 51.6% males) and 20 healthy controls (mean age 50.2 ± 16.4 years old and 33.3% males) were analyzed. There were 39 NASH subjects (41.9%) and 54 non-NASH subjects (58.1%) among the NAFLD subjects. Plasma M30 (349 U/L vs. 162 U/L), and serum ALT (70 IU/L vs. 26 IU/L), AST (41 IU/L vs. 20 IU/L) and GGT (75 IU/L vs. 33 IU/L) were significantly higher in NAFLD subjects than in healthy controls. Serum ALT (86 IU/L vs. 61 IU/L), AST (58 IU/L vs. 34 IU/L) and GGT (97 IU/L vs. 56 IU/L) were significantly higher in NASH subjects compared to non-NASH subjects, but no significant difference was observed with plasma M30 (435 U/L vs. 331 U/L). The accuracy of plasma M30, and serum ALT, AST and GGT was good for predicting NAFLD (AUROC 0.91, 0.95, 0.87 and 0.85, respectively) but less so for NASH (AUROC 0.59, 0.64, 0.75 and 0.68, respectively). Serum ALT and AST, but not plasma M30 showed a significant trend with increasing grades of ballooning and lobular inflammation.

Conclusion: The utility of M30 in the detection of NASH in clinical practice appears limited, in comparison to routine biochemical markers.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alanine Transaminase / blood*
  • Aspartate Aminotransferases / blood*
  • Biomarkers / blood
  • Diagnosis, Differential
  • Fatty Liver / blood
  • Fatty Liver / diagnosis*
  • Fatty Liver / pathology
  • Female
  • Humans
  • Keratin-18 / blood*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / blood
  • Non-alcoholic Fatty Liver Disease / diagnosis*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Peptide Fragments / blood*
  • gamma-Glutamyltransferase / blood*

Substances

  • Biomarkers
  • Keratin-18
  • M30 cytokeratin-18 peptide, human
  • Peptide Fragments
  • gamma-Glutamyltransferase
  • Aspartate Aminotransferases
  • Alanine Transaminase

Grants and funding

This study was funded by the University of Malaya Research Grant. Project No.: RG536-13HTM. URL: http://umresearch.um.edu.my/mainpage.php?module=Maklumat&kategori=86&id=62&papar=1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.