The transhepatic endotoxin gradient is present despite liver cirrhosis and is attenuated after transjugular portosystemic shunt (TIPS)

Background: Translocation of gut-derived bacterial products such as endotoxin is a major problem in liver cirrhosis. Methods: To assess the hepatic clearance of bacterial products in individuals with cirrhosis, we tested concentrations of Gram-negative bacterial lipopolysaccharide (LPS), LPS-binding protein (LBP), and the precursor of nitric oxide (NO), L-arginine, in a cohort of 8 stable patients with liver cirrhosis before and after elective transjugular portosystemic shunt (TIPS) implantation, including central venous, hepatic venous, and portal venous measurements. Results: Using an adapted LPS assay, we detected high portal venous LPS concentrations (mean 1743 +/- 819 pg/mL). High concentrations of LPS were detectable in the central venous blood (931 +/- 551 pg/mL), as expected in persons with cirrhosis. The transhepatic LPS gradient was found to be 438 +/- 287 pg/mL, and 25 +/- 12% of portal LPS was cleared by the cirrhotic liver. After TIPS, central venous LPS concentrations increased in the hepatic and central veins, indicating shunting of LPS with the portal blood through the stent. This paralleled a systemic increase of L-arginine, whereas the NO synthase inhibitor asymmetric dimethylarginine (ADMA) remained unchanged, suggesting that bacterial translocation may contribute to the pathogenesis of circulatory dysfunction post-TIPS. Conclusions: This study provides quantitative estimates of the role of the liver in the pathophysiology of bacterial translocation. The data indicate that the cirrhotic liver retains the capacity for clearance of bacterial endotoxin from the portal venous blood and that TIPS implantation attenuates this clearance. Thus, increased endotoxin concentrations in the systemic circulation provide a possible link to the increased encephalopathy in TIPS patients.