Probiotics Are Helpful in Hepatic Encephalopathy: A Meta-analysis of Randomized Trials

Sammy Saab; Duminda Suraweera; Jennifer Au; Elena G. Saab; Tori S. Alper; Myron J. Tong


Liver International. 2016;36(7):986-993. 

In This Article


The results of our meta-analysis indicate that the use of probiotics may have an important role in the management of hepatic encephalopathy. In several analyses, the clinical impact of probiotic use was similar to that of lactulose, but better than the use of placebo (Table 3). For instance, the use of probiotics was found to be effective for preventing progression of MHE to OHE, and decreased hospitalization rated when compared to placebo, but not any more effective than the use of lactulose. Also, the use of probiotics did not affect mortality rates.

Lactulose is very unpalatable. It is sweet, thick syrup associated with a number of adverse effects including anorexia, nausea, abdominal cramps and diarrhoea. Tolerability is limited, and indeed lactulose noncompliance is the most preventable reason for admission because of hepatic encephalopathy.[12] The use of probiotics is an attractive potential alternative to lactulose. Not only are probiotics better tolerated, but in our meta-analysis, they are also as efficacious when compared to no treatment/placebo. MHE has been associated with a reduced 5 year survival rate in those with cirrhosis[36] and probiotics may play a role in management of these patients who have yet to develop OHE.

Probiotics are defined by the World Health Organization as 'life microorganisms, which when administered in sufficient quantities can confer a health benefit' (FAO/WHO). A number of studies have indeed demonstrated the possible health benefits of probiotics. But the health benefits may be disease particular as well as specific bacterial strains and dose dependent.[37] Although the results of our study demonstrate a favourable impact of probiotics in the management of hepatic encephalopathy, there are a number of practical considerations such as optimal treatment duration, dose and viability of microorganisms.[38] Serious adverse effects, including death, have been reported with the use of probiotics, believed from contamination.[39,40] The Food and Drug Administration does not regulate probiotics since manufacturers propose structure/function claims, rather than specific health claims.[41]

There are a number of important limitations to our meta-analysis. First, most studies in our meta-analysis were conducted in India and it therefore may be difficult to extrapolate the results to all parts of the world. Environmental and dietary factors may contribute to the efficacy of probiotics in the treatment of hepatic encephalopathy. Another limitation is the variability in probiotics used in the studies analysed. Probiotics differ in the amount and bacteria strains used.[42] Indeed, a variety of probiotics were used in the studies of our meta-analysis. These probiotics may potentially be harmful to patients who are immune-suppressed or -compromised. The benefits seen in our meta-analysis may not be generalizable to patients who have severe hepatic decompensation. Equally important, the majority of trials were open labelled. Thus, the benefits of probiotics may have been unintentionally overestimated. Heterogeneity is always a concern when conducting misanalyses, however, no significant heterogeneity was present in comparisons made in this meta-analysis.

Several meta-analyses have been published comparing the use probiotics to lactulose or placebo.[43–47] Our study is the most up to date meta-analysis comprised of many references not previous included in previously published meta-analysis.[43–45] We included 14 randomized control trials and assessed the efficacy of probiotics compared to both placebo and lactulose. Our meta-analysis assessed several outcomes not consistently measured by others such as mortality[44,45,47] and hospitalization.[45,46] In one meta-analysis, reduction in plasma ammonia was found with the use of probiotics but no improvement in clinical outcomes was noted.[43]

In conclusion, probiotics may be useful as part of an armamentarium against hepatic encephalopathy. The findings of this meta-analysis provide evidence that probiotics are more effective than no treatment/placebo in decreasing hospitalization rates, and preventing progression to OHE in patients with underlying MHE. However, the use of probiotics had no impact on mortality rates.