Effect of probiotic VSL#3 in the treatment of minimal hepatic encephalopathy: A non-inferiority randomized controlled trial

Abstract

Aim: 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.

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.

Keywords: chronic liver disease; cirrhosis; lactulose; non-inferiority trial; probiotics.