Variceal Recurrence, Rebleed Rates, and Alterations in Clinical and Laboratory Parameters Following Post Variceal Obliteration in Cirrhotic Patients

© 2011, INASL 21 Ex-vivo Treatment of Neutrophils with a p38-MAPK Agonist in Patients with Acute and Chronic Liver Failure and Elevated Arterial Ammonia Improves Their Bacteriocidal Capacity A Nishtala, NJ Taylor, RD Abeles, JA Wendon, DL Shawcross Institute of Liver Studies and Transplantation, King’s College London School of Medicine at King’s College Hospital, Denmark Hill, London, UK Background: Ammonia reduces neutrophil phagocytic and bacteriocidal capacity. Neutrophils swell in response to ammonia exposure and activation of the p38-MAPK pathway has been implicated in protecting the neutrophil against osmotic shock and normalizing neutrophil phagocytic dysfunction. In patients with acute (ALF) and chronic liver failure (CLF) with elevated arterial ammonia, we hypothesized that treating neutrophils ex vivo with isoproterenol, a β non-specific adrenergic receptor and p38-MAPK agonist would improve neutrophil bacteriocidal capacity. Aims and Methods: Out of 20 patients (10 ALF and 10 CLF) enrolled in study of neutrophil function encompassing 125 patients, we investigated the role of ex vivo incubation of neutrophils with an exogenous ammonia load, a p38-MAPK agonist (Isoproterenol) and the specific p38-MAPK antagonist SB203580 (Calbiochem) on neutrophil function. Phagocytic capacity in heparinized whole blood was quantitatively determined by flow cytometry using FITC-labelled opsonized Escherichia coli at baseline, and following incubation for 90 minutes with NH4Cl (200 μmol/L), isoproterenol (2 μmol/L) or SB203580 (40 μmol/L) at 37°C. Results: ALF patients had a median SOFA score of 16 and APACHE II score of 22. CLF patients had median MELD score 27. The median arterial ammonia level in ALF group was 88 and CLF group was 62 μmol/L. Baseline bactericidal capacity was 67% in the ALF group and 72% in the CLF group compared to > 85% in healthy controls. The exogenous ammonia load further reduced neutrophil phagocytic capacity by median of 7.3%. The p38-MAPK agonist isoproterenol significantly abrogated the ammonia-induced phagocytic impairment and improved bacteriocidal capacity (p < 0.007). The p38-MAPK antagonist SB203580 however, exacerbated the ammonia-induced reduction in neutrophil phagocytic capacity by median of 5.2%; p = 0.003. Conclusion: Data shows that in patients with liver failure and elevated arterial ammonia that neutrophil bacteriocidal capacity is impaired. Activation of the p38-MAPK pathway serves as an important cellular protective mechanism against ammonia-induced impairment. Conflict of Interest: None Variceal Recurrence, Rebleed Rates, and Alterations in Clinical and Laboratory Parameters Following Post Variceal Obliteration in Cirrhotic Patients K Arun Kumar, B Siva Subramaniam, V Jayanthi Department of Gastroenterology and Hepatology, Stanley Medical College and Hospital, Chennai Background: Band ligation is considered as an effective method for obliteration of esophageal varices. Injection sclerotherapy is an alternative method. Aim: To determine the natural history of esophageal varices after its obliteration following sclerotherapy. Material and Method: Consecutive patients with endoscopic proven varices between June 2006 and May 2007 were registered. All the patients had an elective or an emergency variceal endoscopic injection with 0.5% sodium tetradecyl sulphate at an interval of 3 weeks. The patients were followed-up in the liver clinic for recurrences of varices, variceal rebleed, changes in clinical, laboratory parameters and hemodynamic changes in portal venous system at 3 monthly intervals for the first year and thereafter at 6 monthly intervals until May 2010. Patients who had an EVL or a devascularization procedure were excluded. Results: A total of 104 patients with cirrhosis were registered. Eradication of varices required a mean of 5 sessions. Eighteen patients with cirrhosis liver had recurrence of varices at the end of 3 years. Twenty patients had Gr I varices and the remaining Gr II. The varices appeared after a mean period of 11.4 months. Only 4 patients rebled following reappearance of varices. A significant improvement in laboratory findings was noted in hemoglobin, platelet count, prothrombin time (PT), and INR. There was a significant improvement in ascites and regression of jaundice following endotherapy in GpI patients (P < 0.05). A significant (P < 0.05) number of patients in Gp I reverted from Child’s C to B or A. Conclusion: The rebleed rates and bleed-related death was significantly low in cirrhotic patients with portal hypertension after sclerotherapy. There was a significant improvement in clinical and laboratory findings after obliteration of esophageal varices. A significant number of patients reverted from Child’s C to B or A. Conflict of Interest: None 03_JCEH-Abstract.indd 21 3/18/2011 11:13:04 AM