Alcoholic liver disease

Important mechanisms responsible for alcohol-induced liver injury include m itochondrial damage and loss of ATP, formation of acetaldehyde- and other a ldehyde-protein adducts, release of reactive oxygen species (ROS) from mito chondrial electron transfer chain, CYP2E1, and activated Kupffer cells (KCs ); weakening of antioxidant defense systems; and increased intestinal perme ability with endotoxemia. Endotoxin interacts with ethanol and/or acetaldeh yde, and such interaction leads to a complex cascade of autocrine and parac rine pathways that involve the release of cytokines (proinflammatory, anti- inflammatory, and mutagenic), chemokines, and eicosanoids. These pathways a re mediated by activation of KCs, induction of proliferation, and other phe notype changes in hepatic stellate cells (HSCs) leading to transformation t o myofibroblasts (the latter is responsible for fibrogenesis, chemotaxis, a nd contractility, therefore contributing to portal hypertension, angiogenic response, and release of additional cytokines), and stimulation of sinusoi dal cells (SECs) to release adhesive molecules and cytokines. Recent data i mplicate a likely role of apoptosis as a mechanism of hepatocyte cell death in alcoholic liver disease. Curr Opin Gastroenterol 2000. 16:208-218 (C) 2 000 Lippincott Williams & Wilkins, Inc.