Probiotics prevent hepatic encephalopathy in patients with cirrhosis: a randomized controlled trial.

BACKGROUND & AIMS: Hepatic encephalopathy (HE) is associated with a poor prognosis in patients with advanced liver disease. Probiotics alter the intestinal microbiota with non-urease-producing organisms that reduce production of ammonia. We investigated the efficacy of probiotics for the primary prophylaxis of HE. METHODS: We conducted a prospective trial at a tertiary care referral institute in New Delhi, India, from January 2012 through March 2013, of patients with cirrhosis without overt HE (age, 48.6 ± 11.1 y; 96 men and 64 women); 25 were Child-Turcotte-Pugh (CTP) class A, 51 were CTP class B, and 84 were CTP class C. Subjects were assigned randomly to groups given probiotics (1 × 10(8) colony-forming units, 3 times daily; n = 86, 42 with minimal HE) or no test article (control, n = 74; 33 with minimal HE). All subjects underwent psychometric analyses, critical flicker fusion (CFF) threshold assessments, glucose hydrogen breath tests to identify small intestinal bacterial overgrowth (SIBO), and lactulose hydrogen breath tests to measure orocecal transit time (OCTT). The primary end point was the development of overt HE. RESULTS: At baseline, subjects in each group had comparable CTP score, model for end-stage liver disease scores, CFF assessments, psychometric hepatic encephalopathy scores, and OCTT. After a mean follow-up period of 38.6 ± 8.80 weeks for patients given probiotics and 40.3 ± 9.8 weeks for controls, 6 patients given probiotics and 7 controls died (P = .81). Three months of probiotic administration significantly reduced levels of arterial ammonia, SIBO, and OCTT; increased psychometric hepatic encephalopathy scores; and increased CFF thresholds, compared with baseline. Seven subjects in the probiotic group and 14 controls developed overt HE (P < .05; hazard ratio for controls vs probiotic group, 2.1; 95% confidence interval, 1.31-6.53). Psychometric hepatic encephalopathy scores, CTP scores, and SIBO correlated with the development of overt HE. CONCLUSIONS: In a prospective, randomized controlled trial, probiotics were found to be effective in preventing HE in patients with cirrhosis. Trial registration No: CTRI/2012/07/002807.

A randomized, double-blind, controlled trial comparing rifaximin plus lactulose with lactulose alone in treatment of overt hepatic encephalopathy.

OBJECTIVES: Hepatic encephalopathy (HE) is associated with poor prognosis in cirrhosis. Drugs used in the treatment of HE are primarily directed at the reduction of the blood ammonia levels. Rifaximin and lactulose have shown to be effective in HE. We evaluated the efficacy and safety of rifaximin plus lactulose vs. lactulose alone for treatment of overt HE. METHODS: In this prospective double-blind randomized controlled trial, 120 patients with overt HE were randomized into two groups: (group A lactulose plus rifaximin 1,200 mg/day; n=63) and group B (lactulose (n=57) plus placebo). The primary end point was complete reversal of HE and the secondary end points were mortality and hospital stay. RESULTS: A total of 120 patients (mean age 39.4±9.6 years; male/female ratio 89:31) were included in the study. 37 (30.8%) patients were in Child-Turcotte-Pugh (CTP) class B and 83 (69.2%) were in CTP class C. Mean CTP score was 9.7±2.8 and the MELD (model for end-stage liver disease) score was 24.6±4.2. At the time of admission, 22 patients (18.3%) had grade 2, 40 (33.3%) had grade 3, and 58 (48.3%) had grade 4 HE. Of the patients, 48 (76%) in group A compared with 29 (50.8%) in group B had complete reversal of HE (P<0.004). There was a significant decrease in mortality after treatment with lactulose plus rifaximin vs. lactulose and placebo (23.8% vs. 49.1%, P<0.05). There were significantly more deaths in group B because of sepsis (group A vs. group B: 7:17, P=0.01), whereas there were no differences because of gastrointestinal bleed (group A vs. group B: 4:4, P=nonsignificant (NS)) and hepatorenal syndrome (group A vs. group B: 4:7, P=NS). Patients in the lactulose plus rifaximin group had shorter hospital stay (5.8±3.4 vs. 8.2±4.6 days, P=0.001). CONCLUSION: Combination of lactulose plus rifaximin is more effective than lactulose alone in the treatment of overt HE.

Small intestinal bacterial overgrowth and delayed orocecal transit time in patients with cirrhosis and low-grade hepatic encephalopathy.

BACKGROUND: Hepatic encephalopathy (HE) is associated with poor prognosis in cirrhosis. Gut-derived nitrogenous substances play a role in pathogenesis of HE. The present study was conducted to assess small intestinal bacterial overgrowth (SIBO) and prolonged orocecal transit time (OCTT) in cirrhosis and low-grade HE. METHODS: In cross-sectional prospective study, 75 patients were divided into 3 groups: group 1 (no HE, n = 31), group 2 (minimal HE, n = 29), and group 3 (early/grade 1 HE, n = 15). Minimal HE (MHE) was diagnosed when psychometric hepatic encephalopathy score (PHES) was ≤5. Early HE was diagnosed, according to West Haven criteria. All patients underwent glucose hydrogen breath test (GHBT) for SIBO and lactulose hydrogen breath test (LHBT) for OCTT. RESULTS: A total of 29 patients (38.67 %) had MHE and 15 (20 %) had early HE. Prevalence of MHE in Child-Turcotte-Pugh (CTP) class A, B, and C was 33.3, 38.71, and 45 %, respectively, while SIBO was detected in 26 (34.67 %). Prevalence of SIBO was 12.5 % in CTP class A, 41.94 % in CTP class B, and 50 % in CTP class C. Five (16.13 %) patients in no HE group had SIBO as compared to 14 (48.28 %) in MHE group and 7 (46.67 %) in early HE group (p = 0.018). OCTT was 111.13 ± 13.95 min in patients with no HE as compared to 137.59 ± 14.80 min in patients with MHE and 150 ± 15.12 min in patients with early HE (p < 0.001). OCTT was significantly prolonged in patients with SIBO (145 ± 17.49 min) than in those without SIBO (120.71 ± 18.3 min) (p < 0.001). CONCLUSION: SIBO and delayed OCTT are more common with MHE and early HE in patients with cirrhosis.