A Randomised Double Blind Controlled Trial Comparing Rifaximin Plus Lactulose with Lactulose Alone in Treatment of Overt Hepatic Encephalopathy

Abstract

Background: Hepatic encephalopathy (HE) is associated with poor prognosis. Probiotics alter gut flora with nonurease producing organism with decrease ammonia production. Present study assessed efficacy of probiotics for primary prophylaxis of HE. Methods: In prospective randomised controlled trial, patients with no history of overt HE were randomised into: group 1 [Probiotics, n=86, one capsule (110 billion CFU) TDS] and group 2 [control, n = 74]. All patients underwent psychometric tests, critical flicker frequency (CFF), glucose hydrogen breath test (GHBT) for small intestinal bacterial overgrowth (SIBO) and lactulose hydrogen breath test (LHBT) for oro-cecal transit time (OCTT). Primary end point was development of overt HE. Results: One hundred and sixty patients (age 48.6 11.1 years, M:F 96:64) were included. 25 (15.6%), 51 (31.9%) and 82 (52.5%) patients were in CTP class A, B and C respectively. Baseline laboratory parameters, CTP score, MELD score, CFF, psychometric hepatic encephalopathy score (PHES) and OCTT were comparable. Forty two patients (48.8%) in group 1 and 33 (44.6%) in group 2 had minimal HE (P=0.88). Mean follow up of Group 1 and Group 2 patients was 38.6 8.80 vs. 40.3 9.8 weeks (P =0.67). Eleven patients (6.9%) were lost during follow up. Six patients (7.5%) in group 1 and 7 (10.1%) in group 2 died (P =0.81). There was significant improvement in arterial ammonia levels, SIBO, OCTT, PHES, CFF andMHE after 3 months of treatment with probiotics. Seven (8.8%) patients in Group 1 and 14 (20.3%) patients in Group 2 developed overt HE (P <0.05, hazard ratio 2.1, 95% CI, 1.31-6.53). MHE, CTP score and SIBO correlated with development of overt HE. Conclusion: Probiotics are effective in primary prophylaxis of HE.