Cirrhosis and Liver Failure
Keratin-18 and microRNA-122 complement alanine aminotransferase as novel safety biomarkers for drug-induced liver injury in two human cohorts
Article first published online: 14 OCT 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 34, Issue 3, pages 367–378, March 2014
How to Cite
Liver Int. 2014: 34: 367–378
- Issue published online: 7 FEB 2014
- Article first published online: 14 OCT 2013
- Accepted manuscript online: 11 SEP 2013 01:17AM EST
- Manuscript Accepted: 31 AUG 2013
- Manuscript Received: 19 JUN 2013
- European and Developing Countries Clinical Trial Partnership. Grant Numbers: CG_TA.05.40204_005, CT.2005.32030.001
- Swedish Research Council. Grant Number: 348-2011-7383
- National Center for Advancing Translational Sciences
- National Institutes of Health. Grant Number: UL1TR000083
- Medical Research Council. Grant Number: G0700654
- Wellcome Trust Research Fellowship
- drug development;
- HIV ;
Background & Aims
There is a demand for more sensitive, specific and predictive biomarkers for drug-induced liver injury (DILI) than the gold standard used today, alanine aminotransferase (ALT). The aim of this study was to qualify novel DILI biomarkers (keratin-18 markers M65/M30, microRNA-122, glutamate dehydrogenase and alpha-foetoprotein) in human DILI.
Levels of the novel biomarkers were measured by enzyme-linked immunosorbent assay or real-time quantitative reverse-transcription PCR (qRT-PCR) in two human DILI cohorts: a human volunteer study with acetaminophen and a human immunodeficiency virus (HIV)/tuberculosis (TB) study.
In the acetaminophen study, serum M65 and microRNA-122 levels were significantly increased at an earlier time point than ALT. Furthermore, the maximal elevation of M65 and microRNA-122 exceeded the increase in ALT. In the HIV/TB study, all the analysed novel biomarkers increased after 1 week of treatment. In contrast to ALT, the novel biomarkers remained stable in a human cohort with exercise-induced muscular injury.
M65 and microRNA-122 are potential biomarkers of DILI superior to ALT with respect to sensitivity and specificity.