Keratin-18 and microRNA-122 complement alanine aminotransferase as novel safety biomarkers for drug-induced liver injury in two human cohorts.

Abstract

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

M65 and microRNA-122 are potential biomarkers of DILI superior to ALT with respect to sensitivity and specificity.

• Authors: Petra Thulin, Gunnar Nordahl, Marcus Gry, Getnet Yimer, Eleni Aklillu, Eyasu Makonnen, Getachew Aderaye, Lars Lindquist, C Mikael Mattsson, Björn Ekblom, Daniel J Antoine, B Kevin Park, Stig Linder, Alison H Harrill, Paul B Watkins, Björn Glinghammar, Ina Schuppe-Koistinen
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 34 Issue 3 Pg. 367-78 (Mar 2014) ISSN: 1478-3231 [Electronic] United States
• PMID: 24118944 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Biomarkers
• Keratin-18
• M65 antigen, human
• MIRN122 microRNA, human
• MicroRNAs
• Peptide Fragments
• Alanine Transaminase

Topics

• Alanine Transaminase (blood)
• Biomarkers (blood)
• Chemical and Drug Induced Liver Injury (blood, diagnosis)
• Cohort Studies
• Enzyme-Linked Immunosorbent Assay
• Humans
• Keratin-18 (blood)
• MicroRNAs (blood)
• Peptide Fragments (blood)
• Sensitivity and Specificity