Endotoxemia in patients with alcoholic and non-alcoholic cirrhosis and in subjects with no evidence of chronic liver disease following acute alcohol excess

Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: Summary of a symposium

“…Endotoxin is a lipopolysaccharide (LPS) derived from the cell wall of Gram negative bacteria residing in the intestine. The connection between alcohol, endotoxin and liver injury became apparent when researchers observed elevated plasma endotoxin levels in patients affected with ALD (Bode et al, 1987;Fukui et al, 1991). This connection was further confirmed when administration of LPS caused the progression of fatty liver into necroinflammatory changes in a rat model of alcoholic liver injury (Bhagwandeen et al, 1987;Pennington et al, 1997).…”

“…Endotoxemia was reversible in the majority of patients with alcoholic fatty liver and in about 50% of patients with mild alcoholic hepatitis within 1 week following the cessation of alcohol intake (Fukui et al, 1991), further suggesting a direct role of alcohol in increasing plasma endotoxin levels. Liver disease itself may increase plasma endotoxin levels since they were significantly elevated in non-alcoholic cirrhotic patients (Bode et al, 1987;Fukui et al, 1991). However, plasma endotoxin levels were significantly higher in patients with alcoholic cirrhosis than in patients with non-alcoholic cirrhosis (Bode et al, 1987;Fukui et al, 1991), thus implicating alcohol in increasing endotoxin levels.…”

“…Liver disease itself may increase plasma endotoxin levels since they were significantly elevated in non-alcoholic cirrhotic patients (Bode et al, 1987;Fukui et al, 1991). However, plasma endotoxin levels were significantly higher in patients with alcoholic cirrhosis than in patients with non-alcoholic cirrhosis (Bode et al, 1987;Fukui et al, 1991), thus implicating alcohol in increasing endotoxin levels.…”

“…Amount of alcohol appeared to make significant impact on endotoxin levels and liver injury since in these studies healthy control subjects consumed less than 20 g/d of alcohol compared to more than 60 g/d of alcohol by ALD patients. Furthermore, plasma endotoxin levels were also significantly elevated in actively drinking alcoholics without evidence of liver disease (Bode et al, 1987;Nolan, 1989), suggesting that alcohol itself can increase endotoxin levels presumably via increasing intestinal permeability to endotoxin. Endotoxemia was reversible in the majority of patients with alcoholic fatty liver and in about 50% of patients with mild alcoholic hepatitis within 1 week following the cessation of alcohol intake (Fukui et al, 1991), further suggesting a direct role of alcohol in increasing plasma endotoxin levels.…”

Effect of Chronic Coadministration of Endotoxin and Ethanol on Rat Liver Pathology and Proinflammatory and Anti–Inflammatory Cytokines

“…Small amounts of endotoxin regularly pass the mucosal barrier, enter the portal circulation, and are rapidly cleared by the Kupffer cells. However, endotoxin levels are frequently elevated in chronic alcoholics, 4 probably as a result of altered gastrointestinal function including proliferation of gut flora and increased intestinal permeability, as well as reduced phagocytic endotoxin clearance. 5,6 In the experimental intragastric alcohol feeding model blood endotoxin has been found to increase after 2 to 4 weeks of ethanol treatment, 7 and a correlation between endotoxin levels and pathology has been observed.…”