Animal models of drug-induced liver injury

Drug-induced liver injury (DILI) presents unique challenges for consumers, clinicians, and regulators. It is the most common cause of acute liver failure in the US. It is also one of the most common reasons for termination of new drugs during pre-clinical testing and withdrawal of new drugs post-marketing. DILI is generally divided into two forms: intrinsic and idiosyncratic. Many of the challenges with DILI are due in large part to poor understanding of the mechanisms of toxicity. Although useful models of intrinsic DILI are available, they are frequently misused. Modeling idiosyncratic DILI presents greater challenges, but promising new models have recently been developed. The purpose of this manuscript is to provide a critical review of the most popular animal models of DILI, and to discuss the future of DILI research. •Drug-induced liver injury (DILI) is important clinically and during drug development.•Intrinsic and idiosyncratic DILI are the two principal categories if DILI.•Most relevant models for intrinsic DILI are acetaminophen overdose and CCL4.•Idiosyncratic DILI models are less well developed but new ideas are being tested.•Review provides critical discussion on validated and newly emerging models of DILI.