Intestinal glutaminase activity is increased in liver cirrhosis and correlates with minimal hepatic encephalopathy

Background/Aims: We performed the current study to assess the intestinal activity of enterocyte phosphate-activated glutaminase (PAG) in cirrhosis. Methods: Forty-nine cirrhotic patients and 36 control subjects underwent endoscopic duodenal biopsies. Minimal hepatic encephalopathy (MHE) was evaluated using three psychometric tests. Oral glutamine challenge (OGC) was performed and MELD, Child-Pugh and the presence of esophageal varices were recorded. PAG was measured by enzymatic methods. Cerebral magnetic resonance spectroscopy was performed in 10 cirrhotics. Results: PAG was found to be higher in cirrhotics than control subjects 2.4 +/- 1.51 vs. 0.68 +/- 0.57 IU/mg protein (P < 0.001). PAG was also increased in patients with MHE and correlated with MELD, INR, esophageal varices and serum bile acids. A negative correlation was observed between PAG activity and intra-cerebral choline/creatine ratio (r = -0.67; P = 0.035) and a positive correlation with glutamine plus glutamate/creatine ratio (r = 0.78; P = 0.007). In multivariate analysis using backward logistic regression, presence of MHE was the only variable independently related to altered enterocyte PAG. Conclusions: Enterocyte PAG is increased in cirrhotic patients and correlates with MHE. These data support a possible role for intestinal glutaminase in the pathogenesis of hepatic encephalopathy (HE) and could be a new target for future therapies. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.