Review article: the current pharmacological therapies for hepatic encephalopathy

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‐ l ‐aspartate 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 long‐term 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.