Luminary Learning Gastrointestinal Disorder- Issue 1

8  • LUMINARY LEARNING: GASTROINTESTINAL DISORDERS in cirrhosis. Zinc supplement has been shown to increase the speed of urea formation from ammonia and amino acid [38]. Data to support zinc use are very limited and the results are mixed. Furthermore, previous RCTs ( n = 15–90) included chronic HE in the study, thus limiting the generalizability in episodic HE setting [39–41]. The most recent RCT of 79 patients with overt HE showed that zinc supplement was effective in deceasing HE grade and blood ammonia levels [42]. This is the only recent study with evidence to support the use of zinc in HE. The optimal dose of zinc supplement remains unknown. l -Ornithine  l -Aspartate l-Ornithine l-aspartate (LOLA) is not available in the United States, but it is frequently used for HE treatment outside the United States. The mechanism of LOLA is to increase ammonia reduc- tion in both liver and skeletal muscle. In the liver, LOLA can increase urea formation by stimulat- ing ornithine transcarbamylase and carbamoyl phosphate synthetase. In skeletal muscle, LOLA can stimulate glutamine synthesis. Data to support the use of LOLA are mainly in the setting of chronic HE and the efficacy of LOLA in episodic overt HE is not validated [43, 44]. One study from Pakistan evaluated LOLA as adjunctive treatment versus placebo in patients with episodic overt HE and found higher improvement rate of HE grade 2 in LOLA compared to placebo group [45]. Branched-Chain Amino Acids Branched-chain amino acids (BCAAs) consist of valine, leucine, and isoleucine. In skeletal muscle, BCAAs are the substrate for glutamate which is used to synthesize glutamine in ammonia detoxification. The decrease in BCAA level and the increase in aromatic acids have been observed in cirrhosis and hepatic encephalopathy [46]. Studies have evaluated the effects of BCAAs, either intravenously or orally. For cirrhotic patients, two RCTs found that BCAAs improved impor- tant composite end points of death/hospitalization metrics in one study [47] and hepatic failure, variceal bleeding, hepatocellular carcinoma, and mortality in a second study [48]. In the recent meta-analysis of 16 RCTs with 827 patients with hepatic encephalopathy [49], BCAAs had a bene- ficial effect on hepatic encephalopathy (RR 0.76, 95% CI 0.63–0.92) but there was no difference in mortality (RR 0.88, 95% CI 0.69–1.11). Currently, the European Society for Parenteral and Enteral Nutrition (ESPEN) guideline provides a grade A recommendation for the use of BCAA-enriched enteral formula in patients with hepatic encephalopathy who require enteral nutrition [50]. For parenteral nutrition, ESPEN guideline provides a grade A recommendation for the use of BCAAs in hepatic encephalopathy grades 3 and 4 [51]. Percutaneous Embolization of Large Portosystemic Shunts Patients with large portosystemic shunts usually present with persistent HE resulting in episodic hospital admission and coma. In some patients with HE, large portosystemic shunts are accessible