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 α (TNFα). 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 TNFα-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 TNFα-receptors. Soluble TNFα-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.
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 α (TNFα). However, the hepatic elimination of endotoxin in cirrhoticpatients 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 TNFα-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 TNFα-receptors. Soluble TNFα-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.
Authors: Murat M M Harputluoglu; Ramazan Dertli; Baris Otlu; Ulvi Demirel; Ozkan Yener; Yilmaz Bilgic; Mehmet Ali Erdogan; Yahya Atayan; Yasir Furkan Cagin Journal: Dig Dis Sci Date: 2016-01-02 Impact factor: 3.199
Authors: M J Nielsen; J Lehmann; D J Leeming; R Schierwagen; S Klein; C Jansen; C P Strassburg; F Bendtsen; S Møller; T Sauerbruch; M A Karsdal; A Krag; J Trebicka Journal: Dig Dis Sci Date: 2015-07-03 Impact factor: 3.199
Authors: Jonel Trebicka; Aleksander Krag; Stefan Gansweid; Peter Schiedermaier; Holger M Strunk; Rolf Fimmers; Christian P Strassburg; Fleming Bendtsen; Søren Møller; Tilman Sauerbruch; Ulrich Spengler Journal: PLoS One Date: 2013-12-26 Impact factor: 3.240
Authors: Christian Jansen; Hannah Eischeid; Jan Goertzen; Robert Schierwagen; Evrim Anadol; Christian P Strassburg; Tilman Sauerbruch; Margarete Odenthal; Jonel Trebicka Journal: PLoS One Date: 2014-07-28 Impact factor: 3.240