title: Toward predictive models for drug-induced liver injury in humans: are we there yet?
abstract: Drug-induced liver injury (DILI) is a frequent cause for the termination of drug development programs and a leading reason of drug withdrawal from the marketplace. Unfortunately, the current preclinical testing strategies, including the regulatory-required animal toxicity studies or simple in vitro tests, are insufficiently powered to predict DILI in patients reliably. Notably, the limited predictive power of such testing strategies is mostly attributed to the complex nature of DILI, a poor understanding of its mechanism, a scarcity of human hepatotoxicity data and inadequate bioinformatics capabilities. With the advent of high-content screening assays, toxicogenomics and bioinformatics, multiple end points can be studied simultaneously to improve prediction of clinically relevant DILIs. This review focuses on the current state of efforts in developing predictive models from diverse data sources for potential use in detecting human hepatotoxicity, and also aims to provide perspectives on how to further improve DILI prediction.
authors: Division of Bioinformatics & Biostatistics, National Center for Toxicological Research, The US Food & Drug Administration, Jefferson, AR, USA.
authors: Minjun
authors: M
authors: Chen
authors: Halil
authors: H
authors: Bisgin
authors: Lillian
authors: L
authors: Tong
authors: Huixiao
authors: H
authors: Hong
authors: Hong
authors: H
authors: Fang
authors: Jürgen
authors: J
authors: Borlak
authors: Weida
authors: W
authors: Tong
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology*; D019295:Computational Biology; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000145:classification / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D043922:Toxicogenetics / Q000639:trends
chemical_list: D015415:Biomarkers; D004364:Pharmaceutical Preparations