An Update on Animal Models of Alcohol-Associated Liver Disease.

Am J Pathol

Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas 66160, USA; Department of Internal Medicine, Division of Gastroenterology, Hepatology & Mobility, University of Kansas Medical Center, Kansas City, Kansas 66160, USA. Electronic address:

Published: January 2025

Alcohol-associated liver disease (ALD) is a significant global health concern and a leading cause of liver disease-related deaths. However, the treatment options are limited due to the lack of animal models that accurately replicate ALD pathogenesis. An ideal ALD animal model should have pathological characteristics similar to those of human ALD, with a clear pathological process and ease of drug intervention. Over the years, researchers have focused on developing ideal ALD pre-clinical animal models by testing various methods, such as ad libitum drinking water with ethanol, acute single large doses of ethanol gavage, multiple alcohol gavages in a short period, the Lieber-Decarli liquid diet feeding model, the intragastric infusion model, and the Gao-binge model. With the increasing occurrence of obesity and metabolic dysfunction-associated steatotic liver disease, a new category of metabolic and alcohol-associated liver disease (MetALD) is also emerging. Studies have investigated the combined effects of a high-fat diet combined with binge alcohol or drinking water containing ethanol to mimic MetALD. In addition to mice, other species such as rats, guinea pigs, zebrafish, and non-human primates have also been tested to establish ALD pre-clinical models. This review aims to summarize current animal ALD models, particularly the emerging MetALD models, with the hope of providing a valuable reference for establishing more effective animal models in ALD studies in the future.

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http://dx.doi.org/10.1016/j.ajpath.2024.11.011DOI Listing

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