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

Publication date

2020

Authors

Weaver, Richard J
Blomme, Eric A
Chadwick, Amy E
Copple, Ian M
Gerets, Helga H J
Goldring, Christopher E
Guillouzo, Andre
Hewitt, Philip G
Ingelman-Sundberg, Magnus
Jensen, Klaus Gjervig

Editors

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Supervisors

Document Type

Article
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Abstract

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.

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Citation

Weaver, R J, Blomme, E A, Chadwick, A E, Copple, I M, Gerets, H H J, Goldring, C E, Guillouzo, A, Hewitt, P G, Ingelman-Sundberg, M, Jensen, K G, Juhila, S, Klingmüller, U, Labbe, G, Liguori, M J, Lovatt, C A, Morgan, P, Naisbitt, D J, Pieters, R H H, Snoeys, J, van de Water, B, Williams, D P & Park, B K 2020, 'Managing the challenge of drug-induced liver injury : a roadmap for the development and deployment of preclinical predictive models', Nature Reviews. Drug Discovery, vol. 19, pp. 131–148. https://doi.org/10.1038/s41573-019-0048-x