Lactulose, rifaximin or branched chain amino acids for hepatic encephalopathy: what is the evidence?

Metab Brain Dis. 2013 Jun;28(2):221-5. doi: 10.1007/s11011-012-9372-0. Epub 2012 Dec 29.


Hepatic encephalopathy (HE) is a serious complication of acute and chronic liver disease associated with severe morbidity and mortality. We performed updated random effects meta-analyses to evaluate the evidence for non-absorbable disaccharides (lactulose and lactitol), rifaximin and branched chain amino acids (BCAA). A meta-analysis of randomized trials showed that, compared with placebo or no intervention, non-absorbable disaccharides have beneficial effects on HE manifestations and prevention of HE episodes. The addition of rifaximin to non-absorbable disaccharides versus rifaximin alone was more beneficial than non-absorbable disaccharides used alone on both outcome measures. Likewise, a meta-analysis of randomised controlled trials found that oral BCAA supplements have beneficial effects on manifestations of HE compared with control supplements. The effect was found in a variety of clinical settings. No convincing effects of intravenous BCAA for episodic HE were identified. In conclusion, evidence-based treatment recommendations for patients with HE should include non-absorbable disaccharides combined with rifaximin or BCAA. Additional evidence is needed to evaluate the effect of combining all three interventions.

Publication types

  • Review

MeSH terms

  • Amino Acids, Branched-Chain / therapeutic use*
  • Anti-Bacterial Agents / therapeutic use*
  • Disaccharides / metabolism
  • Disaccharides / therapeutic use
  • Evidence-Based Medicine
  • Gastrointestinal Agents / therapeutic use*
  • Hepatic Encephalopathy / drug therapy*
  • Humans
  • Lactulose / therapeutic use*
  • Rifamycins / therapeutic use*
  • Rifaximin


  • Amino Acids, Branched-Chain
  • Anti-Bacterial Agents
  • Disaccharides
  • Gastrointestinal Agents
  • Rifamycins
  • Lactulose
  • Rifaximin