Dispelling myths in the treatment of hepatic encephalopathy.

CONTEXT: Guidelines for the treatment of hepatic encephalopathy suggest ammonia reduction as the main focus, based on strategies to reduce ammonia's generation and absorption in the colon by using lactulose and a reduced protein diet. STARTING POINT: Two studies provide compelling and provocative data questioning the relevance of these interventions. Bodils Als-Nielsen and colleagues, in a systematic review of randomised trials, found insufficient evidence about whether non-absorbable disaccharides are beneficial (BMJ 2004; 328: 1046-50). In a small randomised study, Juan Cordoba and colleagues showed that diets with normal protein content can be administered safely during episodic hepatic encephalopathy due to cirrhosis and that protein restriction does not have any beneficial effect during such episodes (J Hepatol 2004; 41: 38-43). WHERE NEXT: Two approaches to new therapies for hepatic encephalopathy are needed. First, it is important to focus on the interorgan metabolism of ammonia. The small intestine and kidneys might be important producers of ammonia, and muscle is an important organ that can remove ammonia. Novel therapies targeting these organs reduce ammonia. Second, research is needed to explore factors other than ammonia that might be important in hepatic encephalopathy, including the synergistic role of inflammation. The lack of conclusive data about the efficacy of any treatment supports the view that placebo-controlled trials of newer agents are needed and ethical. The emphasis should shift to aggressive management of the precipitating event.