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

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

doi:10.1038/s41573-019-0048-x

Journal articles

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

Christopher E Goldring ¹ André Guillouzo ² Philip G Hewitt ³ Magnus Ingelman-Sundberg ⁴ Klaus Gjervig Jensen Satu Juhila Ursula Klingmüller ⁵ Gilles Labbe ⁶ Michael J Liguori ⁷ Cerys A Lovatt ⁸ Paul Morgan ⁹ Dean J Naisbitt ¹ Raymond H H Pieters ¹⁰ Jan Snoeys ¹¹ Bob van de Water ¹² Dominic P Williams ⁹ B Kevin Park ^{1, *} Richard J Weaver ^{13, *} Eric A Blomme ⁷ Amy E Chadwick ¹ Ian M Copple ¹ Helga H J Gerets ¹⁴

* Corresponding author

1 University of Liverpool

2 NuMeCan - Nutrition, Métabolismes et Cancer

3 Merck Research Laboratories

4 Karolinska Institutet [Stockholm]

5 Division Systems Biology of Signal Transduction, German Cancer Research Center (DKFZ)

6 SANOFI Recherche

7 Abbvie Inc. [North Chicago]

8 GlaxoSmithKline

9 AstraZeneca

10 University Medical Center [Utrecht]

11 Janssen Research & Development

12 Leiden University

13 IRIS - Institut de Recherches Internationales Servier [Suresnes]

14 UCB BioPharma [Braine l’Alleud, Belgium]

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.

Keywords : Adverse effects Drug discovery Preclinical research

Document type :

Journal articles

Domain :

Life Sciences [q-bio]

Life Sciences [q-bio] / Human health and pathology / Hépatology and Gastroenterology

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https://hal-univ-rennes1.archives-ouvertes.fr/hal-02397617
Contributor : Laurent Jonchère <>
Submitted on : Wednesday, June 16, 2021 - 4:11:06 PM
Last modification on : Monday, June 21, 2021 - 4:08:59 PM

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

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

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