Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease.

Background/Aims: No information is yet available about the influence of alcohol abuse on the translocation of larger molecules (M(r)>1200) through the intestinal mucosa in man. The present study aimed to determine the intestinal permeability to macromolecules in patients with chronic alcohol abuse and mild to more advanced stages of liver disease, and to measure the concentration of endotoxins in the plasma, as these compounds derive from the intestinal flora and are suspected to contribute to the development of alcoholic liver disease (ALD). Methods: The permeability to polyethylene glycol M(r) 400, M(r) 1500, M(r) 4000, and M(r) 10 000 and endotoxin plasma concentrations were measured in 54 patients with alcoholic liver disease, 19 of them with cirrhosis, and in 30 non-alcoholic healthy controls. Results: Permeability to polyethylene glycol M(r) 400 was found to be unchanged in patients with ALD in comparison to healthy controls, whereas polyethylene glycol M(r) 1500 and M(r) 4000 were recovered in about twice as high concentrations in the urine of ALD patients (p<0.01). Polyethylene glycol M(r) 10 000 was detected significantly less frequently in urine from healthy controls (0/30) than in urine of patients with alcoholic liver disease (20/54, p<0.01). Endotoxin concentrations in the plasma of alcoholics were increased more than 5-fold compared to healthy controls (p<0.01). Conclusions: The results of this study indicate that alcohol abuse impairs the function of the intestinal barrier, which might enhance the translocation of bacterial toxins, thereby contributing to inflammatory processes in alcoholic liver disease.