Abstract

Background and Aims: Minimal hepatic encephalopathy (MHE) is a prevalent asymptomatic condition, whose diagnosis is difficult due to the lack of a gold standard test. Oral glutamine challenge (OGC) has been found to increase blood ammonia in patients with cirrhosis which could lead to significant cognitive impairment. The aim of our study was to evaluate the value of OGC in improving the performance of psychometric tests and arterial blood ammonia for the diagnosis of MHE. Secondary we followed the risk for development of overt hepatic encephalopathy (OHE). Methods: Fifty-four patients (male/female: 34/20; mean age 59.5yrs) with cirrhosis and 13 healthy controls matched by sex and age were included. Follow-up lasted 12 months. MHE was assessed using the psychometric hepatic encephalopathy score (PHES). Arterial ammonia blood concentrations and PHES were evaluated preand post-60 minutes of a 20 g oral glutamine load. Statistical analysis used paired t-test, relative operating characteristics (ROC) and multivariate logistic regression analysis. Results: At baseline, 29 (53.7%) out of 54 patients met the criteria for MHE, while post glutamine challenge, 43 patients (79.63%) had MHE (p < 0.0001). Arterial blood ammonia levels had significantly raised after glutamine challenge in the cirrhotic patients (baseline vs post glutamine: 85.2±20.8mg/dL vs 159.82±66.01mg/dL, p < 0.0001) as compared to controls values which remained unchanged. ROC analysis showed a pathological glutamine tolerance cut-off value of 124mg/dl. For baseline arterial blood ammonia the AUROC was 0.54 (CI: 0.402–0.680, p = 0.58), with no significant change post glutamine challenge (AUROC = 0.53, CI: 0.389–0.667, p = 0.77). In the follow-up 16 patients (29.62%) developed OHE. In multivariate model, MELD score (OR = 1.5187, 95%CI: 1.0690–2.1574, P = 0.0197), but not Child Pugh class, arterial blood ammonia, esophageal varices grading, was a strong independent predictor of OHE. Conclusions: In cirrhotic patients, OGC appears to improve the performance of psychometric tests, but not arterial blood ammonia for the diagnosis of MHE. MELD score has proven to be independently related with OHE in the follow up. Acknowledgements: This work was made possible by the project ‘Doctoral Scholarships for increasing competitiveness in the medical and pharmaceutical field’ POSDRU/88/1.5/S/58965.

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