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A randomized controlled trial comparing lactulose, probiotics, and L-ornithine L-aspartate in treatment of minimal hepatic encephalopathy

Mittal, Vibhu Vibhasa; Sharma, Barjesh Chandera; Sharma, Praveenb; Sarin, Shiv Kumara

European Journal of Gastroenterology & Hepatology: August 2011 - Volume 23 - Issue 8 - p 725–732
doi: 10.1097/MEG.0b013e32834696f5
Original Articles: Liver Failure

Background Minimal hepatic encephalopathy (MHE) impairs daily functioning and health-related quality of life (HRQoL). The modalities of treatment of MHE have not been adequately studied.

Aims To compare lactulose, probiotics, and L-ornithine L-aspartate (LOLA) in treatment of MHE and effect on HRQoL by Sickness Impact Profile questionnaire.

Methods Consecutive patients with cirrhosis were screened for MHE. MHE was diagnosed by two or more abnormal psychometric tests (number/figure connection tests A and B, block design test, picture completion test). Patients were randomized to no treatment (GpA), lactulose 30–60 ml/twice per day (GpB), probiotics 110 billion colony forming units twice in a day (GpC), LOLA 6 g three times per day (GpD) for 3 months. Arterial ammonia and HRQoL assessment using SIP questionnaire was done at baseline and at 3 months.

Results One hundred and sixty (49.69%) of 322 patients with cirrhosis had MHE. After 3 months, MHE recovered in GpA four (10%), GpB 19 (47.5%), GpC 14 (35%), and GpD 14 (35%). MHE improved significantly in all three treatment groups (GpB, GpC, GpD) compared with no treatment (GpA) (P=0.006). Overt hepatic encephalopathy developed in nine (5.6%) of 160 patients; GpA four (10%), GpB one (2.5%), GpC two (5%), and GpD two (5%), respectively. There was significant improvement in SIP score in GpB (6.98±4.1), GpC (6.24±3.4), and GpD (7.33±3.8) versus GpA (1.05±2.6), P value of less than 0.001. The decrease in SIP score correlated with an improvement in MHE on multivariate analysis but there was no correlation with the type of intervention offered. There was no significant change in arterial ammonia level after therapy in GpA (−0.52±7.8 μmol/l). Arterial ammonia level in GpB (−8.47±5.8 μmol/l), GpC (−7.31±7.9 μmol/l), and GpD (−9.61±9.3 μmol/l) were significantly more than GpA (P<0.0001).

Conclusion Lactulose, probiotics, and LOLA significantly improve MHE and HRQoL in patients with chronic liver disease.

aDepartment of Gastroenterology, G.B. Pant Hospital, University of Delhi

bDepartment of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India

Correspondence to Dr Barjesh Chander Sharma, DM, Department of Gastroenterology, Room 203, Academic Block, G.B. Pant Hospital, New Delhi 110002, India Tel: +91 9718599203; fax: +91 11 23219222; e-mail:

Received November 12, 2010

Accepted March 3, 2011

© 2011 Lippincott Williams & Wilkins, Inc.