Journal Article

Managing the challenge of drug-induced liver injury: a roadmap for the development and deployment of preclinical predictive models

Williams, Dominic P, Klingmüller Ursula, Lovatt, Cerys A, Goldring, Christopher E, Guillouzo Andre, Jensen, Klaus Gjervig, Juhila Satu, Liguori, Michael J, Ingelman-Sundberg Magnus, Blomme, Eric A, Pieters Raymond H H, Gerets Helga H J, Morgan, Paul, Naisbitt, Dean J, Chadwick, Amy E, Kevin, Park B, Labbe Gilles, Snoeys, Jan, van de Water Bob, Copple, Ian M, Hewitt, Philip G, Weaver, Richard J

2020

Overview

Drug-induced liver injury (DILI) is a patient-specific, temporal, multifactorial pathophysiological process that cannot yet be recapitulated in a single in vitro model. Current preclinical testing regimes for the detection of human DILI thus remain inadequate. A systematic and concerted research effort is required to address the deficiencies in current models and to present a defined approach towards the development of new or adapted model systems for DILI prediction. This Perspective defines the current status of available models and the mechanistic understanding of DILI, and proposes our vision of a roadmap for the development of predictive preclinical models of human DILI.Current preclinical models poorly predict the potential of a new drug candidate to cause drug-induced liver injury (DILI) in humans. Here, Park and colleagues discuss current understanding of the mechanisms mediating DILI and, through an academic–industry collaboration, propose a roadmap for the development of predictive preclinical models of human DILI.

• Publisher: Nature Publishing Group
• Subject: Drugs / Liver / Mortality / Pharmaceutical industry / Physiology / Test systems