Stanciu C

The implications of oxidative stress and antioxidant therapies in Inflammatory Bowel Disease: Clinical aspects and animal models.

Inflammatory bowel disease (IBD), including Crohns disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder characterized by alternating phases of clinical relapse and remission. The etiology of IBD remains largely unknown, although a combination of patients immune response, genetics, microbiome, and environment plays an important role in disturbing intestinal homeostasis, leading to development and perpetuation of the inflammatory cascade in IBD. As chronic intestinal inflammation is associated with the formation of reactive oxygen and reactive nitrogen species (ROS and RNS), oxidative and nitrosative stress has been proposed as one of the major contributing factor in the IBD development. Substantial evidence suggests that IBD is associated with an imbalance between increased ROS and decreased antioxidant activity, which may explain, at least in part, many of the clinical pathophysiological features of both CD and UC patients. Hereby, we review the presently known oxidant and antioxidant mechanisms involved in IBD-specific events, the animal models used to determine these specific features, and also the antioxidant therapies proposed in IBD patients.

203 ORAL GLUTAMINE CHALLENGE – DOES IT IMPROVE REVEALING MINIMAL HEPATIC ENCEPHALOPATHY IN CIRRHOSIS?

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.