Rifaximin Improves Psychometric Performance and Health-Related Quality of Life in Patients With Minimal Hepatic Encephalopathy (The RIME Trial)

Cirrhotics with minimal hepatic encephalopathy (MHE) have a poor health-related quality of life (HRQOL). Treatment of MHE is still evolving. The aim of this double-blind randomized pilot study was to assess the efficacy of rifaximin in improving neuropsychometric (NP) test performance and HRQOL in patients with MHE.MHE was diagnosed if any two NP tests (number and figure connection tests, picture completion, digit symbol, and block design tests) were deranged beyond 2 s.d. of normal. HRQOL was assessed using the sickness impact profile (SIP) questionnaire.A total of 486 patients with cirrhosis were screened and 284 were found eligible. Out of these 115 (40.9%) had MHE, of which 21 refused consent and 94 were randomized to receive placebo (n=45) and rifaximin (n=49; 1200 mg/day) for 8 weeks. At the end of treatment, significantly more number of patients in rifaximin group showed reversal of MHE (75.5% (37/49) vs. 20% (9/45) in placebo group; P<0.0001). Rifaximin group also showed significant reduction in mean number of abnormal NP tests (baseline, 2.35 (95% confidence interval (CI), 2.17-2.53); 2 weeks, 1.29 (95% CI, 1.02-1.56), P=0.002; 8 weeks, 0.81 (95% CI, 0.61-1.02), P=0.000), compared with placebo group (baseline, 2.31 (95% CI, 2.03-2.59); 2 weeks, 2.03 (95% CI, 1.74-2.31); 8 weeks, 1.97 (95% CI, 1.69-2.25), P>0.05). The mean total SIP score also improved significantly in rifaximin group (baseline, 11.67 (95% CI, 10.31-13.03); 8 weeks, 6.45 (95% CI, 5.59-7.30); P=0.000) compared with placebo group (baseline, 9.86 (95% CI, 8.66-11.06); 8 weeks, 8.51 (95% CI, 7.35-9.67); P=0.82). Improvement in HRQOL correlated with improvement in NP tests. Rifaximin was well tolerated.Rifaximin significantly improves both cognitive functions and HRQOL in patients with MHE.