title: Effect of probiotic VSL#3 in the treatment of minimal hepatic encephalopathy: A non-inferiority randomized controlled trial.
abstract: OBJECTIVE
  Minimal hepatic encephalopathy (MHE) impairs daily functioning and health-related quality of life in chronic liver disease (CLD). Lactulose is the standard treatment but has side-effects. Probiotics have an encouraging role in MHE. The aim of the present study was to test whether probiotics are non-inferior to lactulose in improving MHE.
  
  
  METHODS
  Patients with CLD (n = 227) were screened for MHE using neuropsychometric tests (number connection tests A and B [or figure connection tests A and B]) and/or neurophysiological test (P-300 auditory event-related potential), and 120 (53%) were diagnosed with MHE by abnormal tests. MHE patients were randomized to lactulose (30-60 mL/day) or probiotic (four capsules of VSL#3; total of 450 billion CFU/day) for 2 months. Response was defined as normalization of tests. Serum ammonia was measured by commercial kit.
  
  
  RESULTS
  Of 120 patients randomized, 40 in the lactulose arm and 33 in the probiotic arm completed 2 months of intervention. MHE improved in 25 (62.5%) patients taking lactulose and 23 (69.7%) taking probiotics. The effect size of difference of improvement in MHE between lactulose and probiotic was 0.072 per per-protocol analysis and 0.040 as per intention to treat analysis (within -20% of non-inferiority margin). Serum ammonia was comparable between groups at baseline and 2 months; it decreased in patients in whom MHE improved, while increased in patients with no improvement in MHE.
  
  
  CONCLUSIONS
  The probiotic VSL#3 was non-inferior to the standard therapy, lactulose in the treatment of MHE. Improvement in MHE correlated with reduction of ammonia levels.
authors.affiliation: Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Venigalla
authors.initials: V
authors.lastname: Pratap Mouli
authors.affiliation: Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Jaya
authors.initials: J
authors.lastname: Benjamin
authors.affiliation: Department of Neurology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Mamta
authors.initials: M
authors.lastname: Bhushan Singh
authors.affiliation: Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Kalaivani
authors.initials: K
authors.lastname: Mani
authors.affiliation: Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Sushil Kumar
authors.initials: SK
authors.lastname: Garg
authors.affiliation: Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Anoop
authors.initials: A
authors.lastname: Saraya
authors.affiliation: Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Yogendra Kumar
authors.initials: YK
authors.lastname: Joshi
keywords: chronic liver disease; cirrhosis; lactulose; non-inferiority trial; probiotics