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Abstract
Although most same-stage non-alcoholic fatty liver disease (NAFLD) patients exhibit similar histologic sequelae, the underlying mechanisms appear to be highly heterogeneous. Therefore, it was recently proposed to redefine NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) in which other known causes of liver disease such as alcohol consumption or viral hepatitis do not need to be excluded. Revised nomenclature envisions speeding up and facilitating anti-MAFLD drug development by means of patient stratification whereby each subgroup would benefit from distinct pharmacological interventions. As human-based in vitro research fulfils an irrefutable step in drug development, action should be taken as well in this stadium of the translational path. Indeed, most established in vitro NAFLD models rely on short-term exposure to fatty acids and use lipid accumulation as a phenotypic benchmark. This general approach to a seemingly ambiguous disease such as NAFLD therefore no longer seems applicable. Human-based in vitro models that accurately reflect distinct disease subgroups of MAFLD should thus be adopted in early preclinical disease modeling and drug testing. In this review article, we outline considerations for setting up translational in vitro experiments in the MAFLD era and allude to potential strategies to implement MAFLD heterogeneity into an in vitro setting so as to better align early drug development with future clinical trial designs.
Original language | English |
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Article number | 161 |
Number of pages | 19 |
Journal | Biomedicines |
Volume | 10 |
Issue number | 1 |
DOIs | |
Publication status | Published - 13 Jan 2022 |
Bibliographical note
Funding Information:This work was funded by grants of Research Foundation Flanders (12H2216N, 1S73019N and G042019N), Onderzoeksraad Vrije Universiteit Brussel, Brussels Environment of the Brussels-Capital Region and the Research Chair Mireille Aerens for the development of Alternatives to Animal Testing. Artwork from Servier Medical Art was partially used for making figures.
Funding Information:
Funding: This work was funded by grants of Research Foundation Flanders (12H2216N, 1S73019N and G042019N), Onderzoeksraad Vrije Universiteit Brussel, Brussels Environment of the Brussels-Capital Region and the Research Chair Mireille Aerens for the development of Alternatives to Animal Testing.
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
Keywords
- NAFLD
- MAFLD
- NASH
- Liver
- Drug development
- Pharmacology
- In vitro
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