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

Abstract and Introduction


Background: Hepatic encephalopathy (HE) is a major complication of cirrhosis and is associated with decreased survival and increased health care utilization.

Aim: The aim of this study was to evaluate the efficacy of probiotics in the management minimal hepatic encephalopathy HE (MHE) and overt HE (OHE) in comparison to no treatment/placebo and lactulose.

Methods: The main outcomes measured were mortality, improvement in MHE, progression to OHE in patients with MHE and hospitalization. We calculated odds ratios (OR) with 95% confidence intervals (CI). Study heterogeneity was assessed using the I 2 statistic.

Results: Fourteen studies totalling 1152 patients were included in the analysis. The use of probiotics had no impact on the overall mortality when compared to either lactulose (OR: 1.07, 95% CI: 0.47–2.44, P = 0.88) or no treatment/placebo (OR: 0.69, 95% CI: 0.42–1.14, P = 0.15). When probiotics was compared to no treatment/placebo, it was associated with a significant improvement in MHE (OR: 3.91, 95% CI: 2.25–6.80, P < 0.00001), decreased hospitalization rates (OR: 0.53, 95% CI: 0.33–0.86, P = 0.01) and decreased progression to overt hepatic encephalopathy (OR: 0.40, 95% CI: 0.26–0.60, P < 0.0001). However when compared to lactulose, probiotics did not show a significant difference in improvement of MHE (OR: 0.81, 95% CI: 0.52–1.27, P = 0.35), hospitalization rates (OR: 1.02, 95% CI: 0.52–1.99, P = 0.96) or progression to overt hepatic encephalopathy (OR: 1.24, 95% CI 0.73–2.10, P = 0.42).

Conclusions: Overall the use of probiotics was more effective in decreasing hospitalization rates, improving MHE and preventing progression to OHE in patients with underlying MHE than placebo, but similar to that seen with lactulose. The use of probiotics did not affect mortality rates.


Hepatic encephalopathy (HE) refers to the altered mental status that occurs in the setting of advanced liver disease.[1] There are two forms of HE currently recognized – covert, which included minimal hepatic encephalopathy (MHE) and Grade 1 HE, and overt HE (OHE), which includes Grade 2–4.[2] The diagnosis of covert HE requires specialized instruments.[2] In contrast, patients with OHE present with symptoms ranging from personality changes to frank coma.[2] The presence of HE increases healthcare utilization and liver-related mortality, and the ability to learn, which can persist even after liver transplantation.[3–7] The development of HE not only affects patients' quality of life but also that of their care givers.[8,9]

The management of HE is centred on altering the bacterial milieu in the intestines.[10] Currently, there are two major pharmacologic interventions in the treatment of HE: lactulose and rifaximin.[2,11] The use of lactulose is limited by adverse effects including nausea, anorexia and abdominal cramps.[12] Rifaximin is well tolerated, but is only indicated by the Food and Drug Administration for reducing of risk of OHE recurrence.[13,14] There is increasing use of alternative therapies such as branched chain amino acids and probiotics.[15,16] Probiotics, in particular, are readily available and may have a role in variety of gastrointestinal disorders.[17–19] The proposed mechanism by which probiotic use can decrease symptoms of HE is by altering gut flora, which in turn decreases the production and absorption of gut derived bacterial toxins.[17]

Several studies have suggested a potential benefit in the use probiotics for the management of hepatic encephalopathy. However, results have been inconsistent. The objective of the present meta-analysis was to systematically evaluate the clinical impact of probiotics on hepatic encephalopathy. Specifically, we were interested in assessing the impact of probiotics on overall mortality, hospitalization, treatment of MHE and MHE progression to OHE.