4.7 Review

Animal models of drug-induced liver injury

Journal

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2018.08.037

Keywords

Acetaminophen; Carbon tetrachloride; Intrinsic hepatotoxicity; Idiosyncratic hepatotoxicity; Immune tolerance

Funding

  1. AASLD Foundation Pinnacle Research Award
  2. University of Arkansas for Medical Sciences
  3. National Institutes of Health (NIH) [R01 DK102142, P20 GM103549, P30 GM118247]
  4. UAMS - NIH [U54 TR001629]

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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.

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