Pathogenesis of alcoholic fatty liver disease: Molecular and cellular changes

Alcohol-related liver disease (ALD) is a significant public health issue, leading to liver injuries, including fatty liver, hepatitis, and cirrhosis. The COVID-19 pandemic has exacerbated the problem by increasing alcohol abuse and hospitalisations for ALD. Since there are no approved therapies for ALD, promoting abstinence from alcohol is the primary approach. However, the mechanisms by which alcohol induces fat accumulation in the liver, the disease's initial stage, are not fully understood. This knowledge gap hampers the development of new treatments for ALD. This review aims to explore research on alcohol-induced fatty liver and compare it with metabolic-associated fatty liver disease. The goal is to merge these findings with current knowledge of ALD and hepatic lipid metabolism, including fatty acid oxidation, lipogenesis, and very-low-density lipoprotein (VLDL) secretion. Besides lipid metabolism, factors like inflammation, oxidative stress, cellular hypoxia, and autophagy also contribute to ALD's development and progression. By identifying gaps in understanding the molecular mechanisms of ALD progression, this review suggests future research directions. It emphasises how alcohol disrupts hepatic lipid metabolism, highlighting mechanisms leading to alcohol-associated fatty liver disease and other harmful effects of alcohol abuse.