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Amino Acid Challenge in Patients with Cirrhosis and Control Subjects: Ammonia, Plasma Amino Acid and EEG Changes

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Abstract

Background/aims: The pathogenesis of hepatic encephalopathy (HE) is controversial. We have therefore studied the effect of induced hyperammonaemia in man. Patients and 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 μmol/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). Conclusion: 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.

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Acknowledgments

This research was supported by a grant from the late Dame Catherine Cookson. Mr. J. Gilroy produced the amino acid mixture, Dr. S.T. Kometa and Mr. A. Davidson assisted with the statistical and EEG analyses, respectively.

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Authors and Affiliations

  1. Department of Medicine, University of Newcastle upon Tyne, NE1 7RU, Newcastle, UK

    Hanan Al Mardini, Andrew Douglass & Christopher Record

  2. Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne, NE1 4LP, UK

    Christopher Record

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  1. Hanan Al Mardini
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  2. Andrew Douglass
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  3. Christopher Record
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Correspondence to Christopher Record.

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Mardini, H.A., Douglass, A. & Record, C. Amino Acid Challenge in Patients with Cirrhosis and Control Subjects: Ammonia, Plasma Amino Acid and EEG Changes. Metab Brain Dis 21, 1–10 (2006). https://doi.org/10.1007/s11011-006-9006-5

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  • DOI: https://doi.org/10.1007/s11011-006-9006-5

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