1Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
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.
To test whether probiotics is non-inferior to lactulose in improving MHE.
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.
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.
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.