Quantitative Systems Toxicology Approaches to Understand and Predict Drug-Induced Liver Injury.

The DILI-sim Initiative is a public-private partnership using quantitative systems toxicology to build a model (DILIsym) capable of understanding and predicting liver safety liabilities in drug candidates. The effort has provided insights into mechanisms underlying dose-dependent drug-induced liver injury (DILI) and interpatient differences in susceptibility to dose-dependent DILI. DILIsym may be useful in identifying drugs capable of causing idiosyncratic hepatotoxicity. DILIsym is used to optimize interpretation of traditional and newer serum biomarkers of DILI. DILIsym results are considered in drug development decisions. In the future, it may be possible to use DILsym predictions to justify reduction in size of some clinical trials.