The role of probiotics in the treatment of minimal hepatic encephalopathy. A prospective, randomized, placebo-controlled, double-blind study

Abstract

Background-Aim: Minimal hepatic encephalopathy (MHE) is the mildest form in the spectrum of hepatic encephalopathy (HE) and describes patients with cirrhosis who have no clinical symptoms of brain dysfunction but perform worse on psychometric tests compared with healthy subjects. It is considered an important disorder that may seriously impair daily functioning and quality of life in patients with cirrhosis. In this prospective study, we investigated the potential role of a probiotic in the treatment of MHE, in patients with cirrhosis. Methods: In a period of 18 months, we screened 142 consecutive patients without overt HE for MHE using both, psychometric (number connection test, NCT) and neurophysiological (brainstem auditory evoked potentials, BAEP) modalities. MHE was defined by abnormality on at least one test modality. Seventy eight (55%) patients diagnosed with MHE and 72 of them were equally randomized into Lactobacillus plantarum 299v at a dose of 1010 units per sachet (Lp299v) or identical placebo, given twice a day for a period of 12 weeks. All tests were repeated on the 12-week visit. Results: Seventy two patients (62 men, mean (SD) age: 59 (10), 58% alcoholic cirrhosis, mean (SD) Child-Pugh score: 6.4 (1.6), 46% Child-Pugh A, mean (SD) MELD score: 11.9 (3.6)) were randomized to receive Lp299v (n=37) or placebo (n=35). At baseline, there were no significant differences between the groups in demographics, liver function tests, serum fasting NH3 levels or performance of psychometric and neurophysiological tests. One patient in the placebo group withdrew consent. Two patients in the Lp299v group and one patient in the placebo group stopped study because of side-effects. Six patients in the placebo group versus none in the Lp299v group developed overt HE during the 12-week trial. The adherence of patients who completed the study was excellent (>80%). After 12 weeks, MHE was reversed in 21 patients (57%) of the probiotic group but in only 3 patients (8.6%) who received placebo and the difference was statistically significant (p<0.001). Moreover, the performance of the NCT test significantly improved in the treatment group (p=0.02) as well as the performance of the BAEP (p=0.03). Serum fasting NH3 levels significantly decreased in the treatment group (p=0.015) while no changes were found in the placebo group. Conclusions: We have shown that the administration of a probiotic (Lp299v) achieved a significant rate of MHE reversal compared to placebo in patients with liver cirrhosis and it might be considered as a valuable alternative for the treatment of MHE.