Abstract and Introduction
Abstract
Background Minimal hepatic encephalopathy (MHE) is characterised by subtle neurocognitive deficits without overt clinical manifestations. Although several trials have individually evaluated the role of prebiotics, probiotics and synbiotics, there is yet no consensus on the management of MHE.
Aim To estimate the efficacy of prebiotics, probiotics and synbiotics in MHE in randomised controlled trials.
Methods MEDLINE, EMBASE, CINAHL and the Cochrane Database of Systematic Reviews were searched for published studies in all languages. Inclusion and exclusion criteria were defined a priori. Pooled relative risk and heterogeneity were estimated as the measures of association.
Results Nine studies met our inclusion criteria. Use of prebiotics, probiotics and synbiotics significantly reduced the pooled relative risk (RR) of no improvement of MHE (RR 0.40, 95% CI 0.32–0.50; P < 0.001). Upon subgroup analysis, five studies with lactulose showed significant reduction of risk of no improvement of MHE (RR 0.34, 95% CI 0.24–0.47; P < 0.0001) with no inter-trial heterogeneity. In two trials each of probiotics and synbiotics, their use was associated with significant beneficial effects (RR 0.41, 95% CI 0.26–0.65; P < 0.0001 and RR of 0.51, 95% CI 0.32–0.80; P = 0.004 respectively). There were no major adverse events though probiotics and synbiotics were better tolerated than lactulose.
Conclusions The use of prebiotics, probiotics and synbiotics was associated with significant improvement in minimal hepatic encephalopathy. Among individual agents, lactulose appears to have the most beneficial effect, followed closely by probiotics and synbiotics.
Introduction
Rikkers et al. first described subclinical hepatic encephalopathy in cirrhotic patients who by conventional neurological and mental status examination appeared normal but had abnormalities in psychometric tests. Now recognised as Minimal Hepatic Encephalopathy (MHE), it is a part of spectrum along hepatic encephalopathy characterised by abnormalities in psychometric and neurophysiological tests without overt clinical symptoms. Incidence of MHE ranges from 30 to 84% in patients with chronic liver disease. MHE is an under diagnosed problem, but its effect on daily activities could be profound as it impairs attention span and reaction time. Wein et al. showed that MHE impairs fitness to drive. Similar observations by Bajaj et al. in this subpopulation of cirrhotics confirm that MHE is a strong predictor for traffic violations and accidents. Cirrhotics with MHE have poor health related quality of life and impaired daily functioning as confirmed by lower scores on the sickness impact profile (SIP). MHE impairs employability; up to 60% of blue collar workers and 23% of white collar workers maybe unfit for working.
The major treatment modalities for MHE have been similar to that of overt hepatic encephalopathy (OHE): targeting ammonia production and absorption. As the gut microbiota play an important role in the generation of ammonia, its modulation using prebiotics, probiotics and synbiotics have been evaluated by several small studies as a therapeutic option for MHE. Prebiotics are defined as a nondigestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thus improves host health. Probiotics are 'live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance'. The combination of prebiotics and probiotics is known as a synbiotic.
The studies using these agents (prebiotics probiotics and synbiotics) have been conducted in a small number of patients with short treatment duration. As a result of seemingly inadequate data, patients with MHE often go untreated, thus potentially subjecting them to all its complications. Pooled results of the available trials would give more conclusive and stronger evidence about the role of gut based therapy. Hence, we conducted a meta-analysis of available randomised controlled trials (RCT) to further ascertain the effect of prebiotics probiotics and synbiotics and resulting gut flora modulation on course of MHE. As MHE remains undertreated, evaluating the efficacy of the available treatment options is of critical importance.