Department of Gastroenterology, G B Pant Hospital, New Delhi, 110002, India. Electronic address: email@example.com.
BACKGROUND & AIMS:
Hepatic encephalopathy (HE) is associated with 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 primary prophylaxis of HE.
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 (48.6±11.1 y old; 96 men and 64 women); 25 were Child Turcotte Pugh (CTP) class A, 51 class B, and 84 class C. Subjects were randomly assigned to groups given probiotics (1x108 CFU, 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 (LHBT) to measure oro-cecal transit time (OCTT). The primary endpoint was development of overt HE.
At baseline, subjects in each group had comparable CTP, model for end-stage liver disease, CFF, and 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 probiotics administration significantly reduced levels of arterial ammonia, SIBO, and OCTT; increased psychometric hepatic encephalopathy scores (PHES); 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). PHES, CTP scores, and SIBO correlated with development of overt HE.
In a prospective, randomized controlled trial, probiotics were found to be effective in preventing HE in patients with cirrhosis.