Probiotics are not better than lactulose in people with hepatic encephalopathy

Hepatic encephalopathy is a brain dysfunction involving neurological and psychiatric changes associated with liver insufficiency or portal-systemic shunting with a severity that ranges from minor symptoms to coma. There have been reported differences in gut microbiota between those with and without hepatic encephalopathy. A previous Cochrane systematic review including 38 randomised clinical trials on non-absorbable disaccharides (lactulose and lactitol) versus control interventions concluded non-absorbable disaccharides may benefit people with hepatic encephalopathy compared with placebo/no intervention. However, it is not clear whether probiotics benefit people with hepatic encephalopathy.

A recent Cochrane review, led by Prof. Angela Webster from the Sydney School of Public Health at The University of Sydney (Australia), has found that probiotics may not be better than lactulose for hepatic encephalopathy.

Of the 21 included randomised clinical trials, which included 1420 participants, 14 trials compared a probiotic with placebo or no treatment and 7 trials compared a probiotic with lactulose. The authors classified 19 of the 21 trials at high risk of bias (low-quality evidence).

When  probiotics were compared with placebo or no treatment, no effect on all-cause mortality was found. However, incomplete resolution of symptoms and adverse effects when considering the development of overt hepatic encephalopathy were lower for participants treated with probiotics, and there was no reported septicaemia attributable to the probiotics in any trial. Besides this, plasma ammonia concentration was lower for participants treated with a probiotic. Little effect on improving quality of life was reported for probiotics compared with no intervention.

On the other hand, when probiotics were compared to lactulose, it was uncertain whether probiotics were better regarding effects on all-cause mortality, adverse effects and quality of life. There was no reported septicaemia attributable to probiotics in any trial.

In conclusion, probiotics may improve recovery and may lead to improvements in the development of overt hepatic encephalopathy, quality of life, and plasma ammonia concentrations when compared with placebo or no intervention. However, there is a lack of evidence showing probiotics are more effective than lactulose for hepatic encephalopathy. More research is needed, since this conclusion is based primarily on low-quality evidence.




Dalal R, McGee RG, Riordan SM, Webster AC. Probiotics for people with hepatic encephalopathy. Cochrane Database Syst Rev. 2017; doi: 10.1002/14651858.CD008716.pub3.

Paul Enck
Paul Enck
Prof. Dr. Paul Enck, Director of Research, Dept. of Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Germany. His main interests are gut functions in health and disease, including functional and inflammatory bowel disorders, the role of the gut microbiota, regulation of eating and food intake and its disorders, of nausea, vomiting and motion sickness, and the psychophysiology and neurobiology of the placebo response, with specific emphasis on age and gender contributions. He has published more than 170 original data paper in scientific, peer-reviewed journals, and more than 250 book chapters and review articles. He is board member/treasurer of the European Society of Neurogastroenterology and Motility and of the German Society of Neurogastroenterology and Motility, and has served as reviewer for many international journals and grant agencies.