In addition to disrupting fatty acid synthesis and oxidation, ethanol alters the metabolism of lipid droplets (LD, the storage form of TG) in hepatocytes and the secretion of very low density lipoproteins by the liver. This effect, together with the inhibition of mitochondrial β-oxidation of fatty acids, contributes to the pathogenesis of fatty liver (hepatosteatosis), the initial stage of ALD. Another important pathway of ethanol metabolism involving CYP2E1, involves an increase in the production of ROS, highly reactive molecules that interact and alter lipoprotein lipids, mitochondrial membranes, DNA and proteins, causing the state known as stress oxidative. Unlike ADH and ALDH, which are essentially found only in the liver, CYP2E1 is present in other organs, including the brain, heart, and lungs, so the consequences of ethanol metabolism via this pathway affect numerous tissues. Ethanol-induced ROS formation may also be attributable to overproduction of NADH, damage to mitochondria, and activation of Kupffer cells. Furthermore, ROS stimulate the release of TNF-α from Kupffer cells, which play an important role in the development of inflammatory reactions and are implicated in tissue damage and fibrosis formation in the liver. Metabolites formed after the degradation of alcohol in the liver can also lead to the formation of ROS. Additionally, alcohol facilitates ROS production by reducing levels of antioxidants, agents that can scavenge ROS (e.g., mitochondrial and cytosolic glutathione, vitamin E). Acetaldehyde formed following ethanol oxidation and ROS interact with amino acids and other molecules, potentially resulting in the formation of stable and unstable adducts (e.g., malondialdehyde adduct). Formation of protein adducts in hepatitis... middle of paper ......d of chronic liver disease. Typically, AH is described as a type of acute and chronic liver injury, in which acute events exceed the liver's ability to respond to alcohol-induced damage. The true prevalence is not known, but histological studies of ALD patients suggest that AH may be present in approximately 10%-35% of hospitalized alcoholic patients. However, even individuals with a relatively mild presentation of AH are at high risk of progressive liver damage, with cirrhosis developing in up to 50% of cases. Although abstinence from alcohol does not guarantee complete recovery, the likelihood of AH progressing to permanent damage is greater among those who continue to abuse alcohol. Elucidating the molecular mechanisms and processes associated with the development of alcoholic liver disease in humans is critical to its treatment and prevention..