Keratin-18 and microRNA-122 complement alanine aminotransferase as novel safety biomarkers for drug-induced liver injury in two human cohorts
2014 (English)In: Liver international (Print), ISSN 1478-3223, E-ISSN 1478-3231, Vol. 34, no 3, 367-378 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2014. Vol. 34, no 3, 367-378 p.
HIV, acetaminophen, biomarkers, drug development, hepatotoxicity, liver, plasma, safety, toxicology, tuberculosis
Medical and Health Sciences
Research subject Medicine/Technology
IdentifiersURN: urn:nbn:se:gih:diva-3013DOI: 10.1111/liv.12322OAI: oai:DiVA.org:gih-3013DiVA: diva2:661140
FunderSwedish National Centre for Research in Sports