Trebicka_2011_Eur.J.Gastroenterol.Hepatol_23_1218

BACKGROUND/AIMS: In cirrhosis portal hypertension can promote bacterial translocation and increase serum endotoxin levels. Vice versa, endotoxin aggravates portal hypertension by induction of systemic and splanchnic vasodilation, and by triggering hepatic inflammatory response via tumor necrosis factor alpha (TNFalpha). However, the hepatic elimination of endotoxin in cirrhotic patients with severe portal hypertension, in the absence of acute complications, has not been investigated so far. METHODS: Twenty patients with alcoholic liver cirrhosis received transjugular intrahepatic portosystemic shunt at an event-free interval for either refractory ascites or recurrent bleeding. During the transjugular intrahepatic portosystemic shunt procedure portal and hepatic venous blood samples were obtained and endotoxin levels were measured by a chromogenic limulus-assay. In 16 of these patients an enzyme-linked immunosorbent assay was used to measure levels of the soluble TNFalpha-receptors sTNF-R55 and sTNF-R75. RESULTS: Portal venous endotoxin levels correlated with portal vein velocity (P=0.03) and arterial systolic blood pressure (P=0.007). Portal endotoxin levels correlated with portal venous sTNF-R75-levels (P=0.039; r=0.521) and hepatic venous sTNF-R55-levels (P=0.009; r=0.669). Hepatic venous levels of both sTNF-R55 and sTNF-R75 correlated directly with the model for end-stage liver disease-score, and inversely with cholinesterase. However, we did not find significant differences in endotoxin levels nor in sTNF-R55-levels and sTNF-R75-levels between portal and hepatic venous blood. CONCLUSION: Endotoxin levels correlated with hemodynamic derangement in cirrhotic severe portal hypertension, and with levels of soluble TNFalpha-receptors. Soluble TNFalpha-receptor levels correlated with the severity of liver dysfunction. However, in this study an endotoxin concentration gradient across the liver was absent, suggesting negligible primary hepatic endotoxin elimination in the absence of complications.