New strategies for treating hepatic encephalopathy.

blind, controlled study of glycerol phenylbutyrate in hepatic encephalopathy. Comment Hepatic encephalopathy (HE) is a serious neuro-psychiatric complication of both acute and chronic liver disease. Historically, the role of ammonia accumulation has dominated explanations of the patho-genesis of HE. However, evidence has emerged for a role of other concurrent factors such as inflammation , hyponatremia, neurosteroids, oxidative and nitrosative stress, manganese with cerebral edema. The precise molecular mechanisms that cause these changes in the brain, are not completely understood. 1 The general management of HE focuses on providing supportive care, identifying and treating any precipitating causes, reducing nitrogenous load in the gut, and assessing the need for long-term therapy and liver transplant evaluation. 2,3 A long-term therapeutic intervention to prevent recurrent HE is needed to decrease health care burden, improve quality of life, and improve outcomes for chronically ill patients. One of the most used phar-macology intervention in these patients are nonab-sorbable disaccharides (lactulose or lactitol) consider as the first-line therapy by acting in the in-traluminal gut bacteria promoting the formation of the less permeable ammonium ion (NH41) from ammoniac (NH3) and as an osmotic laxative that decrease the time available for absorption. When compare the use of lactulose versus placebo, the treated patients show less overt HE (11 vs. 28%, p 0.02). 4 Rifaximin is another important long term pharmacological measurement for HE, these oral antimicrobial agent has a gut-selective activity with nonsystemic effect being a safe drug with no increase in the rate of infections or development of bacterial antibiotic resistance. 5 When compared efficacy of rifaximin plus lactulose vs. lactulose alone for treatment of overt HE in a prospective double-blind randomized controlled trial, demonstrated that combination of lactulose plus rifaximin is more effective than lactulose alone in achieving complete reversal of HE (76 vs. 50% p 0.004) and also decrease mortality (23.8 vs. 49.1%, p < 0.05). 6 On the other hand, a very important area in the management of HE consist on nutritional support, being protein and energy one of the most important, in 2013 a International Society for Hepatic Encepha-lopathy and Nitrogen Metabolism Consensus proposed that the optimal daily energy intake should be 35-40 kcal/kg ideal body weight (recommendation 1A) and the optimal daily protein intake should be 1.2-1.5 g/kg ideal body weight (recommendation 1A), small meals should be evenly distributed throughout the day and a late-night and a snack of complex carbohydrate will minimize …