Leaky gut in alcoholic cirrhosis: A possible mechanism for alcohol-inducedliver damage

Objective: Only 30% of alcoholics develop cirrhosis, suggesting that the de velopment of alcohol-induced liver injury requires one or more additional f actors, Animal studies have shown that gut-derived endotoxin is one such fa ctor. Because increased intestinal permeability has been shown to cause end otoxemia, we hypothesized that increased gastrointestinal permeability cont ributes to the pathogenesis of alcoholic liver disease. This study aimed to measure gastroduodenal and intestinal permeability in alcoholics with and without chronic liver disease and in nonalcoholic subjects with chronic liv er disease. Methods: Gastroduodenal permeability was assessed by measuremen t of urinary excretion of sucrose after oral administration. Intestinal per meability was assessed by measurement of urinary lactulose and mannitol aft er oral administration of these sugars. Results: Alcoholics with no liver d isease showed a small but significant increase in sucrose excretion. Alcoho lics with chronic liver disease demonstrated a marked and highly significan t increase in urinary sucrose excretion relative to the controls, to the al coholics with no liver disease, and to the nonalcoholics with liver disease , Alcoholics with chronic liver disease demonstrated a marked and highly si gnificant increase in both lactulose absorption and in the urinary lactulos e/mannitol ratio (alcoholics 0.703 vs controls 0.019, p = 0.01). In contras t, alcoholics with no liver disease and nonalcoholics with liver disease sh owed normal lactulose absorption and normal lactulose/mannitol ratio. Concl usion: Because only the alcoholics with chronic Liver disease had increased intestinal permeability, we conclude that a "leaky" gut may be a necessary cofactor for the development of chronic liver injury in heavy drinkers. (C ) 1999 by Am. Cell. of Gastroenterology.