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Biomarkers of drug-induced liver injury: progress and utility in research,medicine, and regulation |
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| Authors: | Mitchell R. McGill |
| Affiliation: | 1. Department of Environmental and Occupational Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, USA;2. Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA |
| Abstract: | Introduction: The difficulty of understanding and diagnosing drug-induced liver injury (DILI) has led to proliferation of serum and genetic biomarkers. Many applications of these biomarkers have been proposed, including investigation of mechanisms, prediction of DILI during early trials or before initiation of therapy in patients, and diagnosis of DILI during therapy. Areas covered: We review the definition and categories of DILI, describe recent developments in DILI biomarker development, and provide guidance for future directions in DILI biomarker research. Expert commentary: There are major obstacles to DILI biomarker development and implementation, including the low prevalence of idiosyncratic DILI (IDILI), weak associations of IDILI with genetic variants, and lack of specificity of many biomarkers for the liver. Certain serum biomarkers, like miR-122, may have clinical utility in early-presenting patients with either intrinsic or idiosyncratic DILI in the future, while others likely will not find use. Future research should focus on implementation of biomarkers to predict later injury and outcome in early presenters with intrinsic DILI, and on development of biomarkers of adaptation and repair in the liver that can be used to determine if a liver test abnormality is likely to be clinically significant in IDILI. |
| Keywords: | Hepatotoxicity adverse drug reactions idiosyncratic drug toxicity acetaminophen |