Luminary Learning Gastrointestinal Disorder- Issue 1

Latest Concepts in Inpatient Hepatic Encephalopathy Management •  7 A large meta-analysis in 2004 showed that nonabsorbable disaccharides were superior to placebo. However, when only high-quality trials were included, nonabsorbable disaccharides were found to have no effect on HE [24]. The inconsistent finding in this study is most likely explained by the heterogeneity of HE in previous nonabsorbable disaccharide clinical trials. For example, an overt HE episode may occur in the setting of acute liver failure, acute-on-chronic liver failure, or may be precipitated by a reversible precipitating factor [25]. Although a pivotal trial to prove its effective- ness is lacking, nonabsorbable disaccharides continue to be recommended as the first-line therapy because of decades of clinical experience supporting its effectiveness [26]. Rifaximin Rifaximin is a rifampicin derivative and is mostly unabsorbed by the intestine. Rifaximin is Food and Drug Administration (FDA) approved only for prevention of recurrent HE based on a large multicenter randomized trial [27]. Interestingly, it was not effective in preventing HE in a setting of a transjugular intrahepatic portosystemic shunt (TIPS) [28]. For treating episodic overt HE, the data suggests that rifaximin has equivalent efficacy compared to nonabsorbable disaccharides [29–31]. Although rifaximin is better tolerated in most studies compared to lactulose, the ques- tion of using rifaximin as monotherapy for overt HE remains unanswered given the small number of trials. The use of rifaximin in addition to lactulose for overt HE is supported by a randomized controlled trial (RCT) that found a higher proportion of HE reversal in rifaximin and lactulose group compared to lactulose and placebo group (76% vs. 50.8%, P < 0.004) in patients with overt HE [32]. This study also reported a significant decrease in mortality in the rifaximin and lactulose group compared to lactulose and placebo group (23.8% vs. 49.1%, P < 0.05). However, the gener- alizability of this finding is limited because of the higher-than-expected mortality rate observed in the control arm (49.1%) when compared to the reported inpatient mortality due to HE in the United States (15%) [4, 33]. Neomycin, Metronidazole, and Vancomycin Neomycin is a poorly absorbed aminoglycoside. It is used to decrease gut bacteria-derived ammonia and it is approved by FDA for use in episodic overt HE but not chronic HE. Earlier RCTs did not find difference in its efficacy when compared to lactulose [34] or placebo [35]. Neomycin was widely used in the past. However, the evidence for neomycin in episodic overt HE is weak, and its use is complicated by the risk of ototoxicity and nephrotoxicity. There are small trials supporting the short-term use of metronidazole and vancomycin [36, 37]. However, the risk of neurotoxicity and vancomycin-resistant enterococci colonization limit its long-term use. Zinc Zinc is important in ammonia reduction pathways both for ammonia conversion to urea in liver and for ammonia conversion to glutamine in skeletal muscle. Zinc deficiency is very common