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- Title
Keratin-18 and micro RNA-122 complement alanine aminotransferase as novel safety biomarkers for drug-induced liver injury in two human cohorts.
- Authors
Thulin, Petra; Nordahl, Gunnar; Gry, Marcus; Yimer, Getnet; Aklillu, Eleni; Makonnen, Eyasu; Aderaye, Getachew; Lindquist, Lars; Mattsson, C. Mikael; Ekblom, Björn; Antoine, Daniel J.; Park, B. Kevin; Linder, Stig; Harrill, Alison H.; Watkins, Paul B.; Glinghammar, Björn; Schuppe‐Koistinen, Ina
- 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, micro RNA-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 micro RNA-122 levels were significantly increased at an earlier time point than ALT. Furthermore, the maximal elevation of M65 and micro RNA-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 micro RNA-122 are potential biomarkers of DILI superior to ALT with respect to sensitivity and specificity.
- Subjects
BIOMARKERS; LIVER injuries; ALANINE aminotransferase; MICRORNA genetics; GLUTAMATE dehydrogenase; ACETAMINOPHEN
- Publication
Liver International, 2014, Vol 34, Issue 3, p367
- ISSN
1478-3223
- Publication type
Article
- DOI
10.1111/liv.12322