Amino acid challenge in patients with cirrhosis and control subjects: ammonia, plasma amino acid and EEG changes.
OBJECTIVE
The pathogenesis of hepatic encephalopathy (HE) is controversial. We have therefore studied the effect of induced hyperammonaemia in man.


METHODS
108 g of an amino acid mixture was given orally to 18 cirrhotics and 11 control subjects and changes in blood ammonia, EEG and plasma amino acids were observed.


RESULTS
Basal (39+/-6 versus 14+/-2 micromol/l) and 120-min post amino acid (77+/-10 versus 27+/-4) blood ammonia concentrations in cirrhotics were significantly increased compared to healthy controls (p < 0.001). Associated with these changes there was a significant increase in the ratio of slow-to-fast wave activity indicating EEG slowing (+0.41+/-0.16; N=13 versus -0.05+/-0.08; N=8; p=0.036). As expected in cirrhotics, basal valine and leucine concentrations were decreased while phenylalanine, tyrosine and methionine were significantly increased. Although the basal molar ratio of branched chain amino acids to the aromatic amino acids phenylalanine and tyrosine was significantly decreased in cirrhotics (1.5+/-0.2 versus 3.2+/-0.2; p < 0.0001), after the challenge when EEG changes were apparent in cirrhotics, the ratio significantly increased (p < 0.005) in both groups to 2.7+/-0.3 versus 4.1+/-0.3 (p=0.002). In the combined groups, there were significant correlations between EEG ratio change and the 120-min blood ammonia concentration (r=0.498; p=0.022).


CONCLUSIONS
The alterations in plasma amino acid patterns do not support a specific role for any of the amino acid groups in the pathogenesis of hepatic encephalopathy. They are however more in keeping with the direct or indirect role of ammonia.
Al Mardini
Hanan
H
Department of Medicine, University of Newcastle upon Tyne, Newcastle upon Tyne, NE1 7RU, UK.
Douglass
Andrew
A
Record
Christopher
C
D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000008:administration & dosage* / Q000097:blood*; D000641:Ammonia / Q000097:blood*; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D006501:Hepatic Encephalopathy / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D000596:Amino Acids; D000641:Ammonia