Author information

1Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.

Abstract

BACKGROUND: 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 encouraging role in MHE.

AIM: To test whether probiotics is non-inferior to lactulose in improving MHE.

METHODS: Patients with CLD (n=227) were screened for MHE using neuropsychometrics tests - Number Connection Tests A and B (or Figure Connection Tests A and B) and/or neurophysiologic test - P-300 auditory event related potential; 120 (53%) were diagnosed with MHE by abnormal tests. MHE patients were randomized to lactulose [n=60; dose 30-60 ml/d] or probiotic [n=60; dose 4 capsules of VSL# 3; total 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 lactulose and 33 in probiotic arm completed 2 months of intervention. MHE improved in 25/40 (62.5%) patients taking lactulose and 23/33 (69.7%) taking probiotics. The effect size of difference of improvement in MHE between lactulose & probiotic was 0.072 [95% CI (-0.1475, 0.2915)] as per per-protocol analysis and 0.040 [95% CI (-0.19, 0.11)] as per ITT 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.

CONCLUSION: 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.