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.
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: Jennifer D Hosford; Michael E von Fricken; Michael Lauzardo; Myron Chang; Yunfeng Dai; Jennifer A Lyon; John Shuster; Kevin P Fennelly Journal: Tuberculosis (Edinb) Date: 2014-12-18 Impact factor: 3.131
Authors: Rachel J Church; Gerd A Kullak-Ublick; Jiri Aubrecht; Herbert L Bonkovsky; Naga Chalasani; Robert J Fontana; Jens C Goepfert; Frances Hackman; Nicholas M P King; Simon Kirby; Patrick Kirby; John Marcinak; Sif Ormarsdottir; Shelli J Schomaker; Ina Schuppe-Koistinen; Francis Wolenski; Nadir Arber; Michael Merz; John-Michael Sauer; Raul J Andrade; Florian van Bömmel; Thierry Poynard; Paul B Watkins Journal: Hepatology Date: 2018-06-27 Impact factor: 17.425
Authors: Xi Yang; William F Salminen; Qiang Shi; James Greenhaw; Pritmohinder S Gill; Sudeepa Bhattacharyya; Richard D Beger; Donna L Mendrick; William B Mattes; Laura P James Journal: Toxicol Appl Pharmacol Date: 2015-02-21 Impact factor: 4.219