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  • 1. Thulin, Petra
    et al.
    Nordahl, Gunnar
    Gry, Marcus
    Yimer, Getner
    Aklillu, Eleni
    Makonnen, Eyasu
    Aderaye, Getachew
    Lindquist, Lars
    Mattsson, C. Mikael
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's and Mats Börjesson's research group.
    Antoine, Daniel J.
    Park, B Kevin
    Linder, Stig
    Harrill, Alison H
    Watkins, Paul B.
    Glinghammar, Björn
    Schuppe-Koistinen, Ina
    Keratin-18 and microRNA-122 complement alanine aminotransferase as novel safety biomarkers for drug-induced liver injury in two human cohorts2014In: Liver international (Print), ISSN 1478-3223, E-ISSN 1478-3231, Vol. 34, no 3, p. 367-378Article in journal (Refereed)
    Abstract [en]

    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.

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