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EASL position paper on preclinical models of steatotic liver disease

Lookup NU author(s): Professor Quentin AnsteeORCiD, Dr Dina Tiniakos, Professor Fiona OakleyORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2026 European Association for the Study of the Liver.Steatotic liver disease (SLD) comprises a heterogeneous group of liver diseases defined by pathological hepatic lipid accumulation with varying degrees of steatohepatitis and progressive fibrosis, which may culminate in cirrhosis and/or hepatocellular carcinoma. SLD encompasses metabolic dysfunction-associated steatotic liver disease (MASLD), formerly called non-alcoholic fatty liver disease (NAFLD); MetALD, describing patients with MASLD consuming moderately high amounts of alcohol; and alcohol-associated/related liver disease (ALD). In addition, SLD encompasses less common aetiologies, including drug-induced and monogenic causes, as well as cryptogenic disease, which lacks metabolic risk factors or an identifiable cause. As the leading cause of chronic liver disease worldwide, MASLD, including metabolic dysfunction-associated steatohepatitis (MASH), is a complex multisystem disorder associated with extrahepatic organ dysfunction. Consequently, MASLD has become a major focus of multidisciplinary research, driving innovation across hepatology, immunology, cardiometabolism, addiction medicine, nutrition, prevention, and beyond. Over the past two decades, a broad array of in vivo, in vitro, and ex vivo experimental models have been developed to recapitulate diverse aspects of SLD pathophysiology, genetics, inflammation, treatment response, and multi-organ crosstalk, substantially advancing mechanistic understanding and therapeutic development. However, the rapid expansion and heterogeneity of available models have also highlighted the need for improved categorisation, standardisation, and harmonisation in line with evolving disease definitions and clinical concepts. In this EASL position paper, we critically review and classify currently available experimental SLD models and propose key criteria required for their appropriate use across distinct SLD subtypes. These criteria encompass systemic and hepatic metabolism, cardiometabolic comorbidities, histopathology, immunopathology, and molecular features relevant to disease stage and aetiology. This position paper aims to guide informed model selection, promote consistent nomenclature, and enhance rigour and translational relevance in preclinical and experimental SLD research.


Publication metadata

Author(s): Gallage S, Castro RE, Estall J, Tabas I, Anstee QM, Tiniakos DG, Szabo G, Yu J, Desdouets C, Tacke F, Oakley F, Heikenwalder M

Publication type: Article

Publication status: Published

Journal: Journal of Hepatology

Year: 2026

Volume: 85

Issue: 2

Pages: 345-382

Print publication date: 01/08/2026

Online publication date: 26/05/2026

Acceptance date: 28/04/2026

Date deposited: 17/08/2026

ISSN (print): 0168-8278

ISSN (electronic): 1600-0641

Publisher: Elsevier B.V.

URL: https://doi.org/10.1016/j.jhep.2026.04.029

DOI: 10.1016/j.jhep.2026.04.029

ePrints DOI: 10.57711/2nwk-ng79

Data Access Statement: Supplementary data to this article can be found online at https://doi.org/10.1016/ j.jhep.2026.04.029.


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Funding

Funder referenceFunder name
(EP PerMed) and Fundação para a Ciência e a Tecnologia (FCT) grant (PMTargets/0002/2024) and by UID/04138/2025 from FCT (https://doi.org/10.54499/UID/04138/2025)
Agence Nationale de la Recherche (ANR-AAPG2022-CE14-DNAFAT)
CIHR grants; PJT-175155 and PJT-198065.
ERC POC (Faith), the European Commission (Horizon Europe- Mission Cancer, THRIVE, Ref. 101136622)
European Research Council (ERC) Synergy grant ‘Hepatomodulator’
German Research Foundation (SFB/TR 412, Project-ID 535081457, and SFB1382, Project-ID 403224013)
Germany's Excellence Strategy – EXC 3118/1 – project number 533770413. G.S was supported by the NIH R01AAA011576, R01AA020744,
Helmholtz Future topic Inflammation and Immunology, Zukunftssthema ‘Immunology and Inflammation’ (ZT-0027), SFB/TR 412 (Project ID: 535081457)
la Fondation pour la Recherche Médicale (Equipe FRM: EQU201903007824)
IMI2 and IHI research and innovation programs of the European Union under Grant Agreements 777377 (LITMUS), 101132901 (LIVERAIM), 101136259 (EDC-MASLD) and 101136622 (THRIVE)
Institut National de la Santé et de la Recherche Médicale (INSERM)
Max-Eder Junior Research Group Program of the Deutsche Krebshilfe (German Cancer Aid - Project ID: 70116308)
Medical Research Council (MRC) grants; MR/K0019494/1, MR/R023026/1 & UKRI526
Ligue Nationale contre le Cancer (Equipe Labellisée LIGUE 2023)
Newcastle NIHR Biomedical Research Centre, and the Horizon Europe,
NIH grant R01DK133694 and by the Digestive and Liver Disease Research Center of Columbia University Irving Medical Center, funded by NIH grant 5P30DK132710.
R01AA017729, R01AA032418 grants.
nstitut National du Cancer (PAIR obésité INCA/Inca_18713)
seed funding from HI-TRON.
Rainer Hoenig Stiftung, Research Foundation Flanders (FWO) under grant 30826052 (EOS Convention MODEL-IDI)
Rosetrees Trust project grant (PGL22/100014).
SFB/TR 209 (Project ID: 314905040), SFB 1479 (Project ID: 441891347), SFBTR 179 (Project ID: 272983813)

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