Cutting-edge topics in the pathophysiology of alcoholic liver disease

Abstract

Chronic alcohol abuse elicits a wide spectrum of liver diseases ranging from fatty liver to cirrhosis. The initial, modest form of alcoholic liver disease (ALD) is fatty liver, which is reversible upon abstinence, whereas alcoholic hepatitis results in advanced fibrosis and hepatocarcinogenesis. Only a portion of heavy drinkers develop advanced liver diseases, which cannot be simply explained by the differences in genetic polymorphisms of alcohol metabolizing enzymes. Susceptibility to ALD varies among various ethnic groups and gender, and genetic factors such as patatin-like phospholipase encoding 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), and membrane bound O-acyltransferase domain containing 7 (MBOAT7) share a certain role as similar to nonalcoholic steatohepatitis (NASH). Emerging lines of evidence indicate that novel forms of cell death (necroptosis and pyloptosis), dysbiosis of gut microbiota, and altered innate immune responses profoundly contribute to the development of ALD, suggesting potential therapeutic targets.