Altered response to oral glutamine challenge as prognostic factor for overt episodes in patients with minimal hepatic encephalopathy

BACKGROUND/AIMS: We assessed the usefulness of oral glutamine challenge (OGC) and minimal hepatic encephalopathy in evaluating risk of overt hepatic encephalopathy in cirrhotic patients.METHODS: Minimal hepatic encephalopathy (MHE) was inferred using neuro-psychological tests. Venous ammonia concentrations were measured pre- and post-60 min (NH(3)-60m) of a 10 g oral glutamine load. Receiver-operating-characteristic curve analysis indicated a pathological glutamine tolerance cut-off value of NH(3)-60m >128 microg/dl. RESULTS: In healthy control subjects (n=10) ammonia concentrations remained unchanged but increased significantly in cirrhotic patients (from 70.41+/-45.2 to 127.43+/-78.6; P<0.001). In multiple logistic regression analysis, altered OGC was related to Child-Pugh (odds ratio, OR=7.69; 95% confidence interval, CI=1.72-33.3; P<0.01) and MHE (OR=5.45; 95% CI=1.17-25.4; P<0.05). In the follow-up 11 patients (15%) developed overt hepatic encephalopathy (HE). In multivariate analysis OGC (OR=14.5; 95% CI=1.26-126.3) and MHE (OR=1.56; 95% CI=1.02-21.9) were independently related with HE in the follow-up. Patients with MHE and altered OGC showed significantly higher risk of overt HE in the follow-up (60%) than patients without MHE and normal OGC (2.8%) (Log rank test=21.60; P<0.0001). CONCLUSIONS: A pathological OGC in patients with MHE appears to be a prognostic factor for the development of overt hepatic encephalopathy, whereas a normal OGC in patients without MHE could exclude risk of overt HE.