An open-label randomized controlled trial of lactulose and probiotics in the treatment of minimal hepatic encephalopathy.

BACKGROUND AND AIM: Minimal hepatic encephalopathy (MHE) is associated with poor quality of life and increased work disability. Treatment with lactulose and probiotics has shown some benefit. We compared lactulose with probiotics and a combination of lactulose plus probiotics in the treatment of MHE.

PATIENTS AND METHODS: One hundred and ninety cirrhotic patients without overt encephalopathy [Child's A grade 71 patients (37.4%), Child's B grade 72 patients (37.9%), Child's C grade 47 patients (24.7%)] were evaluated by psychometry (number connection tests A and B or figure connection tests A and B) and P300 auditory event-related potential (P300ERP). MHE was diagnosed by abnormal psychometry and/or P300ERP. Patients were randomized to receive lactulose [group A (n=35): dose 30-60 ml/day], probiotics [group B (n=35): dose 1 capsule three times/day, each capsule contained Streptococcus faecalis 60 million, Clostridium butyricum 4 million, Bacillus mesentricus 2 million, lactic acid bacillus 100 million] and lactulose plus probiotics [group C (n=35)] for 1 month. Response was defined by normalization of the abnormal test parameters.

RESULTS: MHE was diagnosed in 105 (55.2%) patients. Of the 105 patients, 75 (71%) had both abnormal psychometry and P300ERP, whereas 90 (86%) had abnormal psychometry alone, and 89 patients (85%) had abnormal P300ERP alone. Significant improvement was seen in abnormal psychometry tests (group A: n=31 vs. n=12, group B: n=29 vs. n=14, group C: n=30 vs. n=10), P300ERP (group A: 376.8+/-22.3 vs. 344.3+/-30.6 ms, group B: 385.4+/-28.5 vs. 355.5+/-27.9 ms, group C: 387.7+/-27.5 vs. 347.7+/-31.5 ms) and venous ammonia levels (group A: 102.3+/-63.1 vs. 69.3+/-33.3 micromol/l, group B: 108.2+/-37.5 vs. 75.7+/-33.0 micromol/l, group C: 96.3+/-27.7 vs. 68.7+/-28.4 micromol/l) in lactulose, probiotics and a combination of lactulose plus probiotics groups after treatment. Normalization of abnormal psychometry and P300ERP was seen in 54.8, 51.6 and 56.6% of patients treated with lactulose, probiotics and lactulose plus probiotics groups, respectively.

CONCLUSION: A total of 55% of the patients with cirrhosis had MHE. Lactulose or probiotics or combinations of both are equally effective in the treatment of MHE.