Patients with MHE showed significant impairment in 11 scales of the SIP, the psychosocial and physical subscores, and in the total SIP. Patients received 30–60 mL of lactulose in two or three divided doses so that the patient passed two to three semi-soft stools per day. Following lactulose therapy for 3 months, both psychometric performance and HRQOL improved; MHE reversed in 64.5% of treated patients compared

with 6.7% in the no-treatment group (P < 0.0001). Significant improvement was found in five (emotional behavior, ambulation, mobility, sleep/rest and recreation and pastimes) of the 12 scales of the SIP and in the total psychosocial and physical sub-scores in the treated patients compared with the untreated patients. Improvement in HRQOL was linked to improvement in cognitive function. A recent study that compared lactulose, a probiotic and LOLA with no treatment, confirmed these findings.67 Lactulose drug discovery or lactitol, both non-absorbable, synthetic disaccharides with multiple effects on gut flora, are regarded as intestinal prebiotics.96 Dietary addition of lactulose can exert a bifidogenic effect accompanied by a favorable effect on colonic NH3 metabolism.97 A meta-analysis of randomized trials of lactulose versus placebo or no intervention in treatment of patients buy ABT-263 with MHE showed that

the treatment with lactulose was associated with improvement in psychometric (cognitive) performance.35 Prebiotics, probiotics or synbiotics (probiotics and fermentable fiber) are effective in treating patients with MHE,63–67 and can also be used as long-term therapy. Liu et al.65 showed that modulation of gut microecology and acidification of gut lumen in patients with liver cirrhosis and MHE by treatment with synbiotics resulted in increased fecal content of non-urease-producing Lactobacillus species, whereas the number of urease-producing pathogenic Escherichia coli see more and Staphylococcal species decreased. This effect persisted for 14 days after

cessation of supplementation. It was associated with a significant reduction in blood ammonia and endotoxin levels and reversal of MHE in nearly 50% of the patients. The severity of liver disease, as assessed according to CTP class, also improved in nearly 50% of the patients. In a recent randomized control trial, supplementation with probiotic yogurt resulted in a significant reversal of MHE in the group receiving yogurt compared to no treatment.63 Treatment with a probiotic preparation also improves HROQL.67 Prebiotics, probiotics or synbiotics are efficacious in the treatment of HE by decreasing bacterial urease activity, pH in the gut lumen, ammonia absorption and total ammonia in the portal blood, and by improving nutritional status of gut epithelium resulting in decreasing intestinal permeability.