Abstract
Background & AimsThere 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.
MethodsLevels 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.
ResultsIn 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.
ConclusionsM65 and microRNA-122 are potential biomarkers of DILI superior to ALT with respect to sensitivity and specificity.
Original language | English |
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Pages (from-to) | 367-378 |
Number of pages | 12 |
Journal | Liver International |
Volume | 34 |
Issue number | 3 |
DOIs | |
Publication status | Published - Mar 2014 |
Keywords / Materials (for Non-textual outputs)
- acetaminophen
- biomarkers
- drug development
- hepatotoxicity
- HIV
- liver
- plasma
- safety
- toxicology
- tuberculosis
- CIRCULATING MICRORNAS
- ALPHA-FETOPROTEIN
- CELL-DEATH
- ACETAMINOPHEN HEPATOTOXICITY
- HEPATOCELLULAR-CARCINOMA
- TRANSAMINASE ACTIVITY
- SERUM BIOMARKERS
- FUNCTION TESTS
- MARKERS
- PROGNOSIS