Alcohol-related Liver Disease

Alcohol injures the liver through a predictable metabolic sequence, not a single hit

The liver metabolises alcohol via alcohol dehydrogenase to acetaldehyde, a directly toxic and reactive compound, and this metabolism itself generates excess NADH, which shifts hepatocyte metabolism towards fat synthesis and away from fat oxidation. The result is progressive fat accumulation within hepatocytes (steatosis) with continued drinking. Acetaldehyde and the oxidative stress of alcohol metabolism also directly injure hepatocytes and activate an inflammatory response, so with sustained heavy intake the picture progresses from simple fatty change to alcoholic hepatitis (hepatocyte injury, inflammation and necrosis) and, with ongoing injury and repair cycles, to fibrosis and ultimately cirrhosis.