Oral glutamine challenge improves the performance of psychometric tests for the diagnosis of minimal hepatic encephalopathy in patients with liver cirrhosis.

BACKGROUND & AIMS Minimal hepatic encephalopathy is difficult to diagnose due to the lack of a gold standard test. Oral glutamine challenge has been found to increase blood ammonia in cirrhosis leading to secondary cognitive impairment. The aim of this study was to evaluate the value of oral glutamine challenge in improving the psychometric performance for the diagnosis of minimal hepatic encephalopathy, and the risk of this condition for overt hepatic encephalopathy in cirrhotic patients. METHODS Fifty-four cirrhotics (34 males; mean age 55.2 years) and 16 healthy controls were included. Minimal hepatic encephalopathy was assessed by the psychometric hepatic encephalopathy score. Arterial ammonia concentrations and psychometric tests were evaluated 60 minutes before and after a 20 g oral glutamine load. Follow-up lasted 12 months. RESULTS At baseline, 29 (53.7%) of 54 patients had minimal hepatic encephalopathy and significantly more (79.63%) post-glutamine (p<0.0001). Baseline arterial ammonia levels significantly raised post-glutamine in cirrhotics (85.2+/-20.8μg/dL versus 159.82 +/- 66.01μg/dL, p<0.0001), while in controls they remained unchanged (p=0.064). For the diagnosis of minimal hepatic encephalopathy, baseline arterial blood ammonia showed an area under the ROC curve of 0.54 (CI95%: 0.402-0.680, p=0.58), with no significant post-glutamine changes (0.53, CI95%: 0.389-0.667, p=0.77). Ten patients (18.51%) developed overt hepatic encephalopathy, among which 9 had minimal hepatic encephalopathy (4 at baseline, 5 post-glutamine). At multivariate analysis, MELD score (1.5187, CI95%: 1.0690-2.1574, p=0.0197) was an independent predictor of the overt hepatic encephalopathy. CONCLUSIONS In cirrhotic patients, an oral glutamine load improves the psychometric diagnostic performance for minimal hepatic encephalopathy. MELD score has been independently related to overt hepatic encephalopathy.