Probiotics in Minimal Hepatic Encephalopathy: A Meta-Analysis

Abstract

Purpose: Minimal hepatic encephalopathy (MHE) is characterized by abnormal neurophysiological testing and absence of clinical symptoms. Attention span and reaction time are reduced, with impaired quality of life and reduced survival. Elevated ammonia is implicated in the pathophysiology; treatment options are directed at lowering it. Probiotics are live microorganisms, beneficial to the host in therapeutic doses. They prevent the proliferation of pathogenic bacteria in the GI tract and hence decrease ammonia production. Several studies have been conducted to identify its role in the management of MHE with variable results. We herein perform a meta-analysis of these studies. Methods: We performed a search on Pubmed and Medview to identify randomized controlled trials (RCT) on probiotics in MHE in the last 20 years. To be eligible, studies had to include at least two randomized groups with a pre post comparison of mean ± standard deviation of serum ammonia levels. Five studies comparing probiotics vs placebo/no treatment and three studies comparing probiotics vs lactulose were included. Analyses were done using Comprehensive Met Analysis 2.2 (Biostat, Englewood, NJ).Figure: [362] Statistical analysis of probiotics vs placebo in MHE.Figure: [362] Statistical analysis of probiotics vs lactulose in MHE.Results: On comparing probiotics with placebo, treatment with probiotics was superior to placebo or no treatment (p=0.006) and to lactulose (p=0.02). The standardized difference (95 % CI) for probiotics vs placebo was 0.44 (0.13, 0.75) while probiotics vs lactulose was 0.32 (0.06, 0.58). Conclusion: The results of the two meta-analyses described above indicate the beneficial role of probiotics in lowering serum ammonia levels in MHE patients. These results compare favorably with lactulose, with possibly fewer adverse effects such as diarrhea and bloating. Large RCT studies are warranted to further validate the role of probiotics in MHE.