title: Effect of rifaximin, probiotics, and l-ornithine l-aspartate on minimal hepatic encephalopathy: a randomized controlled trial.
abstract: OBJECTIVE
  Minimal hepatic encephalopathy (MHE) implies subtle impairment of cognitive functions in the absence of features of overt encephalopathy. We aimed to determine the prevalence of MHE in patients with liver cirrhosis and to find out the effect of rifaximin, probiotics, and l-ornithine l-aspartate (LOLA) individually in reversal of MHE by comparing it with placebo group.
  
  
  METHODS
  This study was carried out in two phases. Phase I included the recruitment of 250 apparently healthy controls and extraction of normative data utilizing three neuropsychometric tests (NPTs) and critical flicker frequency (CFF) test. Phase II consisted of screening and recruitment of patients of MHE followed by drugs trial. A total of 317 cirrhotics were screened; 111 were excluded and the remaining 206 cirrhotics were screened for MHE using NPTs and/or CFF test. Of these, 124 patients with MHE were randomized to receive LOLA (n = 31), rifaximin (n = 31), probiotics (n = 32), for 2 months and were compared with patients who were given placebo (n = 30).
  
  
  RESULTS
  Out of 206 cirrhotics, 124 (60.19%) had MHE. Among these 124 MHE patients, 87 (70.16%) patients had CFF <39Hz, 112 (90.32%) patients with MHE had two or more abnormal NPTs, and 75 (60.48%) patients had abnormality on both the CFF values and more than two abnormal NPTs. Intention-to-treat analysis showed the number of patients who improved after giving treatment were 67.7% (21/31), 70.9% (22/31), 50% (16/32), and 30% (9/30) for LOLA, rifaximin, probiotics, and placebo, respectively. CFF scores and improvement in psychometric tests after treatment were significantly higher (P < 0.05) for LOLA, rifaximin, and probiotics as compared with placebo group.
  
  
  CONCLUSIONS
  Prevalence of MHE is high in patients with cirrhosis of liver. Rifaximin, LOLA, and probiotics are better than giving placebo in patients with MHE.
authors.affiliation: Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
authors.forename: Kapil
authors.initials: K
authors.lastname: Sharma
authors.forename: Sanjay
authors.initials: S
authors.lastname: Pant
authors.forename: Sriprakash
authors.initials: S
authors.lastname: Misra
authors.forename: Manisha
authors.initials: M
authors.lastname: Dwivedi
authors.forename: Alok
authors.initials: A
authors.lastname: Misra
authors.forename: Sushil
authors.initials: S
authors.lastname: Narang
authors.forename: Reshu
authors.initials: R
authors.lastname: Tewari
authors.forename: Ajeet S
authors.initials: AS
authors.lastname: Bhadoria
mesh_terms: D000328:Adult; D004151:Dipeptides / Q000627:therapeutic use*; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006501:Hepatic Encephalopathy / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D008103:Liver Cirrhosis / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D019936:Probiotics / Q000627:therapeutic use*; D012294:Rifamycins / Q000627:therapeutic use*; D000078262:Rifaximin
chemical_list: D004151:Dipeptides; D005765:Gastrointestinal Agents; D012294:Rifamycins; C002939:ornithylaspartate; D000078262:Rifaximin