Post-feeding hyperammonaemia in patients with transjugular intrahepatic portosystemic shunt and liver cirrhosis: role of small intestinal ammonia release and route of nutrient administration

Background-Hyperammonaemia is a pathogenetic factor for hepatic encephalopa thy that may be augmented after a transjugular intrahepatic portosystemic s hunt (TIPS). Experimental data suggest that hyperammonaemia may be caused t o a large extent by metabolism of small intestinal enterocytes rather than colonic bacteria. Aims-To evaluate if ammonia release and glutamine metabolism by small intes tinal mucosa contribute to hyperammonaemia in vivo in patients with liver c irrhosis. Methods-Using TIPS to examine mesenteric venous blood, we measured mesenter ic venous-arterial concentration differences in ammonia and glutamine in pa tients with liver cirrhosis before, during, and after enteral (n=8) or pare nteral (n=8) isonitrogenous infusion of a glutamine containing amino acid s olution. Results-During enteral nutrient infusion, ammonia release increased rapidly compared with the post-absorptive state (65 (58-73) nu 107 (95-119) mu mol /l after 15 min; mean (95% confidence interval)) in contrast with parentera l infusion (50 (41-59) nu 62 (47-77) mu mol/l). This resulted in a higher p ortal ammonia load (29 (21-36) v 14 (8-21) mmol/l/240 minutes) and a higher degree of systemic hyperammonaemia (14 (11-17) nu 9 (6-12) mmol/l/240 minu tes) during enteral than parenteral infusion. The mesenteric venous-arteria l concentration difference in glutamine changed from net uptake to release at the end of the enteral infusion period (-100 (-58 to -141) nu 31 (-47-11 0) mu mol/l) with no change during parenteral nutrition. Conclusions-These data suggest that small intestinal metabolism contributes to post-feeding hyperammonaemia in patients with cirrhosis. When artificia l nutrition is required, parenteral nutrition may be superior to enteral nu trition in patients with portosystemic shunting because of the lower degree of systemic hyperammonaemia.