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From NAFLD to MAFLD: Aligning Translational In Vitro Research to Clinical Insights. | LitMetric

From NAFLD to MAFLD: Aligning Translational In Vitro Research to Clinical Insights.

Biomedicines

Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.

Published: January 2022

AI Article Synopsis

  • - The text discusses the proposal to redefine non-alcoholic fatty liver disease (NAFLD) as metabolic dysfunction-associated fatty liver disease (MAFLD) due to the varied underlying mechanisms among patients, suggesting that existing liver disease causes do not need to be excluded.
  • - This redefinition aims to enhance drug development by allowing for better patient stratification, leading to targeted pharmacological treatments for different subgroups of MAFLD.
  • - The article emphasizes the importance of adapting human-based in vitro models to reflect the specific characteristics of MAFLD for effective preclinical research and drug testing, ultimately improving alignment with clinical trial designs.

Article 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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773802PMC
http://dx.doi.org/10.3390/biomedicines10010161DOI Listing

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