Oral L-ornithine-L-aspartate for patients with overt hepatic encephalopathy treated with lactulose: A randomized, double-blinded, placebo-controlled trial

Abstract

© 2018, Medical Association of Thailand. All rights reserved. Objective: Lactulose is widely used for treating patients with hepatic encephalopathy [HE] despite of no strong evidence of its effectiveness. L-ornithine-L-aspartate [LOLA] can lower serum ammonia level and improve mental state in patients with mild HE. We evaluated the add-on benefit of oral LOLA in patients with grade II-III HE those treated with optimal dose of lactulose. Materials and Methods: In a randomized, double-blinded, placebo-controlled trial, cirrhotic patients with grade II and III HE according to West-Haven criteria those treated with lactulose were stratified randomized by serum creatinine level to receive LOLA (3 grams thrice daily) or placebo for 7 days. The primary outcome was the improvement of mental status, and secondary outcomes were the improvement of the number connection test [NCT], plasma ammonia level, asterixis, electroencephalogram [EEG], portal systemic encephalopathy index [PSEI] and safety. Results: Thirty-five patients with overt HE (grade II25 patients and grade III 10 patients) were assigned to LOLA group (n = 18) or placebo group (n = 17). The LOLA group tended to have improvement of mental status by 90% compared to 84.6% of placebo group at day 7 (p = 1.0) by per-protocol analysis. Both groups also had similar improvement in mental status at day 4, asterixis, EEG and PSEI. Dose of lactulose and daily bowel movement were comparable in both groups. Treatment of infection which was the main precipitating factor, strongly correlated with better mental state in day 7 (p = 0.025). No serious adverse effect of LOLA was found. Conclusion: There was no add-on benefit of oral LOLA for cirrhotic patients with overt HE who were treated with an optimal dose of lactulose. The more effective treatment of HE was to correct the precipitating factors especially infection.