Alcoholic liver disease.
Research has substantiated the role of several mechanisms responsible for alcohol-induced hepatotoxicity. These mechanisms include: oxidative stress and lipid peroxidation; immunogenic processes initiated by formation of protein adducts of acetaldehyde, other aldehydes and 1-hydroxyethyl radicals; and activation of Kupffer cells by endotoxin and subsequent cascade of events that involved cytokines, chemokines, and adhesion molecules. Increasing evidence implicates enhanced intestinal permeability caused by alcohol ingestion as the culprit that leads to endotoxemia. While oxidative stress is important, the principal source of reactive oxygen species that causes alcohol-induced liver injury is hotly debated. Potential sources may include cytochrome P450IIE1, activated Kupffer cells, and mitochondrial electron transfer chain. Apoptosis is likely an important pathway that culminates in hepatocyte cell death. Abstinence, corticosteroids, and enteral nutrition remain the cornerstones in the treatment of alcoholic hepatitis. The efficacies of medications such as S-adenosylmethionine and pentoxifylline will need further confirmation by additional randomized trials before they can be recommended as standard therapies for alcoholic hepatitis.
Lumeng
L
L
Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. llumeng@iupui.edu
Crabb
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DW