Can Lactobacillus acidophilus improve minimal hepatic encephalopathy? A neurometabolite study using magnetic resonance spectroscopy

Abstract

Background and study aims: Minimal hepatic encephalopathy (MHE) is diagnosed when hepatic patients perform worse on psychometric tests compared to healthy controls. This study aimed to evaluate probiotics as alternative therapy in MHE.

Patients and methods: This is an open-label randomised controlled trial, performed in the Department of Tropical Medicine and Infectious Diseases, Tanta University Hospitals, from March 2010 to January 2012. A total of 90 patients with MHE were allocated by simple randomisation to three parallel equal groups. Group A received lactulose, group B a probiotic (Lactobacillus acidophilus) and group C served as the control. After informed consent, patients were tested for gut micrecology, fasting blood ammonia, liver functions and magnetic resonance spectroscopy (MRS) examination to study brain metabolites, mainly choline (Cho), myo-inositol (mI), glutamine+glutamate (Glx) and creatinin (Cre). Patients who developed overt encephalopathy were excluded from analysis. The whole battery of investigations was repeated in the same order after 4weeks.

Results: The probiotic was better tolerated than lactulose. The relative risk reduction (RRR) of developing overt encephalopathy was 60% in the case of lactulose and 80% in the case of probiotic, with a number needed to treat (NNT) of 2.4 and 2.3, respectively. The differential but not total microecology count was significantly shifted towards saccharolytic rather than proteolytic bacteria. The mI/Cre and (Cho+mI)/Glx ratios were significantly increased and the Glx/Cre ratio was significantly reduced after 1month-follow-up in the probiotic group compared to the lactulose group and in both treatment groups compared to the control group.

Conclusion: Both probiotic and lactulose therapy can improve blood ammonia and psychometric tests in MHE and reduce the risk of developing overt encephalopathy. MRS showed more improvement in the levels of brain neurometabolites in the probiotic group.

Keywords: ANOVA; ARR; BDT; Cho; Cre; Creatinine; DST; Glx; HE; HRQOL; LTT; Lactobacillus acidophilus; MHE; MRS; Magnetic resonance spectroscopy (MRS); Minimal hepatic encephalopathy (MHE); NCT-A; NCT-B; NNT; RRR; SDT; absolute risk reduction; block design test; choline; digit symbol test; glutamine–glutamate; health-related quality of life; hepatic encephalopathy; line tracing test; mI; magnetic resonance spectroscopy; minimal hepatic encephalopathy; myo-inositol; number connection test-A; number connection test-B; number needed to treat; one-way analysis of variance; relative risk reduction; serial-dotting test.