Serum biomarkers of drug-induced liver injury: current status and future directions.

Drug-induced liver injury (DILI), caused by drugs and herbal or dietary supplements, remains a serious concern for drug developers, regulators, and clinicians; however, the serum biomarkers utilized to detect and monitor for DILI have not changed in decades and have limitations. Data-driven mathematical modeling that incorporates the release and clearance kinetics of traditional biomarkers has improved their use in the prediction of liver safety liabilities for new drug candidates. Several newer biomarkers have shown promise in terms of liver specificity, in predicting outcome of DILI events, and in providing insight into underlying mechanisms. Qualification and regulatory acceptance of new biomarkers will require their assessment in large numbers of subjects who are receiving a wide range of compounds and that develop a broad spectrum of liver injury. The ongoing and evolving international biomarker consortia should have a major role in this effort which is likely to transform assessment of liver safety in clinical trials and in the clinic. This article is protected by copyright. All rights reserved.