Effect of L-ornithine-L-aspartate on patients with and without TIPS undergoing glutamine challenge: a double blind, placebo controlled trial.
OBJECTIVE
An oral glutamine load in cirrhotic patients awaiting liver transplantation was shown to cause a rise in blood ammonia and psychometric abnormalities which were reversed by hepatic transplantation. L-Ornithine-L-aspartate (LOLA) has been shown to reduce ammonia and improve psychometric function in patients with hepatic encephalopathy. The aim of the present study was to assess the effect of LOLA in healthy patients with cirrhosis and no evidence of clinical encephalopathy after challenging the central nervous system by administration of oral glutamine.


METHODS
Eight cirrhotics (Child's B or C) without transjugular intrahepatic portosystemic shunts (TIPS) and seven with TIPS underwent two oral glutamine (20 g) challenges, receiving LOLA (5 g intravenously) on one occasion and placebo on the other in random order. Psychometric tests, including choice reaction time (CRT) and number connection test, were performed before and after glutamine, together with electroencephalography and blood ammonia.


RESULTS
Mean basal ammonia was 27 (SEM 5) micromol/l in non-TIPS and 76 (10) micromol/l in TIPS patients (p<0.05). Basal CRT 2 was 0.643 (0.033) s in non-TIPS and 0.825 (0.076) s in TIPS patients (p<0.02). In non-TIPS patients, ammonia increased to 36 (10) micromol/l when LOLA was administered and to 62 (13) micromol/l with placebo (p<0.02). There was no alteration in psychometric function in non-TIPS patients after glutamine when LOLA was given but when placebo was given, glutamine caused prolongation of CRT (p=0.02). Glutamine did not affect psychometric function in TIPS patients with or without LOLA.


CONCLUSIONS
This study showed that LOLA ameliorated the deleterious psychometric effects of glutamine in Child's grade B and C patients with cirrhosis without TIPS and supports its use in clinical practice in hepatic encephalopathy.
Rees
C J
CJ
Centre for Liver Research, University of Newcastle Upon Tyne, Newcastle Upon Tyne, UK.
Oppong
K
K
Al Mardini
H
H
Hudson
M
M
Record
C O
CO
D000641:Ammonia / Q000097:blood; D004151:Dipeptides / Q000627:therapeutic use*; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects; D005973:Glutamine; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood / Q000628:therapy*; D008875:Middle Aged; D019168:Portasystemic Shunt, Transjugular Intrahepatic; D011594:Psychometrics
D004151:Dipeptides; D005973:Glutamine; D000641:Ammonia; C002939:ornithylaspartate