Pathogenesis of Alcoholic Liver Disease: Current Insights
Objective of the Review: To take a Look at current insights into the pathogenesis of alcoholic liver disease (ALD). Key Points: Based on the clinical and morphological features, the following three forms (stages) of liver damage can be identified: alcoholic steatosis, steatohepatitis and cirrhosis. Alcoholic steatosis is triggered by alcohol and results from enhanced lipogenesis caused by the activation of lipogenic gene expression and the inhibition of fatty acid oxidation. When inflammation develops, it leads to alcoholic steatohepatitis; ethanol metabolic products, endotoxins, ethanol-induced hypoxia, autophagy and other factors are important contributors. Fibrosis related to ALD is mediated by the activation of TLR4 receptors that is induced by bacterial lipopolysaccharides, the activation of hepatic stellate cells caused by acetaldehyde and the "profibrotic" effects of ethanol. The authors also discuss the mechanisms and conditions required for the transformation of alcoholic liver cirrhosis into hepatocellular carcinoma. Conclusion: In addition to ethanol, there are a number of other factors that contribute to the development of ALD, such as genetic, immune and epigenetic factors. The role of epigenetic factors should be further clarified.