Assessment of non-alcoholic fatty liver disease using serum total cell death and apoptosis markers
Article first published online: 16 OCT 2012
© 2012 Blackwell Publishing Ltd
Alimentary Pharmacology & Therapeutics
Volume 36, Issue 11-12, pages 1057–1066, December 2012
How to Cite
Shen, J., Chan, H. L.-Y., Wong, G. L.-H., Chan, A. W.-H., Choi, P. C.-L., Chan, H.-Y., Chim, A. M.-L., Yeung, D. K.-W., Yu, J., Chu, W. C.-W. and Wong, V. W.-S. (2012), Assessment of non-alcoholic fatty liver disease using serum total cell death and apoptosis markers. Alimentary Pharmacology & Therapeutics, 36: 1057–1066. doi: 10.1111/apt.12091
- Issue published online: 7 NOV 2012
- Article first published online: 16 OCT 2012
- Manuscript Accepted: 28 SEP 2012
- Manuscript Revised: 27 SEP 2012
- Manuscript Received: 15 JUN 2012
- General Research Fund of the Research Grant Council. Grant Number: 477710
The diagnosis of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and fibrosis relies on liver biopsy. Non-invasive assessments are urgently needed.
To evaluate cell apoptotic marker cytokeratin-18 M30 and total cell death markers cytokeratin-18 M65/M65ED for the assessment and monitoring of NAFLD.
A cohort of 147 patients with biopsy-proven NAFLD and 73 controls were enroled, including 51 patients who received paired liver biopsies 36 months apart. Biomarkers were determined by enzyme-linked immunosorbent assay.
M30, M65 and M65ED increased in a stepwise fashion in control subjects, patients with non-NASH, NAFLD and NASH (all P < 0.001). All biomarkers had similarly high accuracy over 0.9 in predicting NAFLD and moderate accuracy around 0.7 in predicting NASH. Among patients with paired liver biopsies, changes in M30, M65 and M65ED positively correlated with disease progression (rho = 0.42, 0.32 and 0.39; P = 0.002, 0.023 and 0.005 respectively), and only changes in M65 and M65ED correlated with fibrosis progression (rho = 0.29, 0.34; P = 0.038, 0.015 respectively). Both M30 and M65 had area under receiver-operating characteristics curve above 0.8 in predicting disease progression. At cut-off of 236 U/L, changes of M65ED had 88% NPV and 59% PPV to exclude and predict fibrosis progression.
Cytokeratin-18 M30 and M65/M65ED have moderate accuracy in detecting non-alcoholic steatohepatitis. Changes in the biomarkers also correlate with histological progression. However, development of new biomarkers is still required to improve the diagnostic accuracy.