Alcoholic liver disease: a new insight into the pathogenesis of liver disease

Excessive alcohol consumption contributes to a broad clinical spectrum of liver diseases, from simple steatosis to end-stage hepatocellular carcinoma. The liver is the primary organ that metabolizes ingested alcohol and is exquisitely sensitive to alcohol intake. Alcohol metabolism is classified into two pathways: oxidative and non-oxidative alcohol metabolism. Both oxidative and non-oxidative alcohol metabolisms and their metabolites have toxic consequences for multiple organs, including the liver, adipose tissue, intestine, and pancreas. Although many studies have focused on the effects of oxidative alcohol metabolites on liver damage, the importance of non-oxidative alcohol metabolites in cellular damage has also been discovered. Furthermore, extrahepatic alcohol effects are crucial for providing additional information necessary for the progression of alcoholic liver disease. Therefore, studying the effects of alcohol-producing metabolites and interorgan crosstalk between the liver and peripheral organs that express ethanol-metabolizing enzymes will facilitate a comprehensive understanding of the pathogenesis of alcoholic liver disease. This review focuses on alcohol-metabolite-associated hepatotoxicity due to oxidative and non-oxidative alcohol metabolites and the role of interorgan crosstalk in alcoholic liver disease pathogenesis.