Portal venous and systemic endotoxaemia in patients without liver disease and systemic endotoxaemia in patients with cirrhosis.
Systemic endotoxaemia without evidence of gram-negative bacterial infection occurs in liver diseases in man. The endotoxaemia is probably due to impaired hepatic clearance of endotoxin absorbed from the gastrointestinal tract, but portal venous endotoxaemia has never been reported in man. By means of the limulus gelation test, portal venous blood from 21 patients without parenchymal liver disease and arterial blood from 21 patients without parenchymal liver disease and 31 patients with cirrhosis was examined for endotoxin. Portal venous endotoxaemia was found in 9 of 21 samples and systemic endotoxaemia was found in 2 of 21 samples from patients without liver disease. Systemic endotoxaemia in cirrhosis occurred with a frequency of 15/31. No relationship to gram-negative bacteraemia was found. Leucocytosis was only seen in endotoxin-positive patients with cirrhosis. In cirrhosis higher levels of E. coli O antibodies were found in endotoxin-positive than in endotoxin-negative patients, supporting the view that the limulus gelation test specifically detects endotoxin (i.e. E. coli O antigen). The study suggests that endotoxin is a normal constituent of portal venous blood in man. The normal human liver clears endotoxin from the portal venous blood. This effect is diminished in cirrhosis, most probably owing to decreased phagocytic function of the liver. The increased humoral immune response in cirrhosis may be related to spillover of endotoxin from the liver.