Novel biomarkers for drug-induced liver injury

[Speaker] Chris Goldring:1
1:MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK

Drug-induced liver injury (DILI) is a leading cause of pharmaceutical attrition and acute liver failure. Challenges in this field include deficiencies in our current endpoints and biomarkers used in preclinical in vivo models, which mean that these models are not sufficiently predictive of human DILI, as well as the fact that no single in vitro model (with associated endpoints and biomarkers) can yet adequately recapitulate the complex nature and multifarious forms of DILI that occur in humans. Therefore there is considerable interest in improving and adopting new human-relevant biomarkers of liver injury, and ensuring that they can help to bridge the current gaps between these models and human DILI. Worldwide efforts are now being directed to improve the liver biomarker status quo, for example evaluating the application of protein biomarkers of liver degeneration and regeneration. In parallel with protein biomarkers, the application of microRNA biomarkers of liver damage will be particularly explored in this talk, building on current knowledge of the strengths and weaknesses of miR-122 as a relatively selective biomarker of liver damage, its measurement, variability and relationship to tissue levels in in vitro and in vivo models and humans. This talk will also explore the broader miR field by assessing other liver miRs, including the role of zonation in expression of liver miRs as well as non-hepatocyte miRs, such as biliary epithelial cell miRs, as these are likely to inform on more than simple damage to one region of the hepatocyte compartment of the liver. Finally, recent improvements in preclinical testing strategies through the assessment of preclinical imaging methods, allowing the field to explore the value of imaging biomarkers, such as magnetic resonance imaging, bioluminescence imaging, as well as functional imaging will also be discussed.
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