Review article: the current pharmacological therapies for hepatic encephalopathy

Abstract

Effective treatment options for hepatic encephalopathy are limited. Based on the principle that intestinal-derived ammonia contributes to the pathogenesis of hepatic encephalopathy, current therapeutic approaches are directed at reducing bacterial production of ammonia and enhancing its elimination.Non-absorbable disaccharides are first-line therapy for hepatic encephalopathy, but published clinical studies evaluating their safety and efficacy are limited. Alternative therapies such as benzodiazepine receptor antagonists, branched-chain amino acids, and L-ornithine-Laspartate also have limited clinical data supporting their use.Studies of antibiotics indicate that they are effective in the treatment of hepatic encephalopathy, but adverse effects and concerns about longterm safety have limited the widespread use of most.Rifaximin is a minimally absorbed antibiotic that concentrates in the gastrointestinal tract and is excreted mostly unchanged in faeces. It has been studied extensively in the treatment of hepatic encephalopathy and appears to confer therapeutic benefits greater than those of placebo and non-absorbable disaccharides and at least comparable with those of systemic antibiotics. Rifaximin was also well tolerated in patients with hepatic encephalopathy and is not associated with clinical drug interactions or clinically relevant bacterial antibiotic resistance.In conclusion, non-absorbed antibiotics such as rifaximin offer a favourable benefit-risk ratio in the treatment of hepatic encephalopathy and may help to improve patient outcomes.

L-carnitine in Hyperammonemia and Hepatic Encephalopathy

“…In HE, an increase of aromatic amino acids compared to branched-chain amino acids has been observed, which could be modified by the intake of branched-chain amino acids (Bass, 2007). Also L-Ornithine-L-Aspartate lowers ammonia levels in blood as it provides substrates for the metabolic conversion of ammonia to urea and glutamine (Kircheis et al, 2002b).…”

“…Another means of treating HA is restriction of dietary protein (a source of ammonia), while caloric intake is provided by glucose and fat. Less investigated to date are L-carnitine and its derivatives, which are suggested to increase fat metabolism and have been suggested to decrease ammonia concentrations in blood by raising metabolic energy production (Bass, 2007).…”

“…However, there are several drugs being examined in research and clinical trials that could benefit patients with HE. Most of them tend to reduce the production and absorption of ammonia from the colon (Bass, 2007;Morgan et al, 2007). Furthermore, non-absorbable disaccharides inhibit bacterial ammonia production in the colon and retard ammonia as non-diffusable ammonium in the intestinal colon (Cammà et al, 1993).…”

“…Furthermore, non-absorbable disaccharides inhibit bacterial ammonia production in the colon and retard ammonia as non-diffusable ammonium in the intestinal colon (Cammà et al, 1993). But in many cases, studies approving the efficacy and safety of the drugs are limited (Bass, 2007). Antibiotics are administered to reduce the quantity of enteric bacteria which produce ammonia.…”

Comparison of Rifaximin, Lactulose With Rifaximin, Lactulose, Branched Chain Aminoacids (Bcaa) in Grade 1 to Grade 3 of Hepatic Encephalopathy- Non Randomized Controlled Trial Study

“…It is active against a variety of aerobic and anaerobic Gram-positive and Gram-negative organisms, as well as protozoal infections. 12,13 Rifaximin acts by inhibiting bacterial ribonucleic acid (RNA) synthesis. The primary mechanism for developing resistance to Rifaximin is chromosomal alteration of the drug target, i.e., DNAdependent RNA polymerase, which is in contrast with the plasmid-mediated resistance that affects other antibiotics.…”