Oral L-ornithine-L-aspartate for Patients with Overt Hepatic Encephalopathy Treated with Lactulose: A Randomized, Double-blinded, Placebo-controlled Trial
Supot Nimanong MD1, Inchaya Sansak MD1, Tawesak Tanwandee MD1, Phunchai Charatcharoenwitthaya MD1, Watcharasak Chotiyaputta MD1, Kanokwan Boonyapisit MD2, Siwaporn Chainuvati MD1
Affiliation : 1 Division of Gastroenterology, Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand 2 Division of Neurology, Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
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 II 25 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.
Keywords : Ammonia, Cirrhosis, Hepatic encephalopathy, Lactulose, L-ornithine-L-aspartate
