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Role of ammonia and inflammation in minimal hepatic encephalopathy

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Abstract

Background: Minimal hepatic encephalopathy (MHE) is common in cirrhosis but its pathophysiologic basis remains undefined. We evaluated whether the presence of MHE was associated with severity of liver disease, ammonia levels or the presence of inflammation and assessed factors determining neuropsychological deterioration accompanying induction of hyperammonemia. Methods: Eighty four cirrhotics were studied. A neuropsychological test battery was performed and blood taken for ammonia, WCC, CRP, nitrate/nitrite, IL-6 and amino acids, before and after, induction of hyperammonemia by administration of a solution mimicking the amino acid composition of haemoglobin (60) or placebo (24). Results: The presence and severity of MHE were independent of severity of liver disease and ammonia concentration but markers of inflammation were significantly higher in those with MHE compared with those without. Induction of hyperammonemia produced deterioration in one or more neuropsychological tests by ≥1 SD in 73.3%. This was independent of the magnitude of change in plasma ammonia and severity of liver disease but was significantly greater in those with more marked inflammation. Conclusion: Our data show that inflammation is an important determinant of the presence and severity of MHE. The change in neuropsychological function following induced hyperammonemia is greater in those with more severe inflammation.

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Abbreviations

MHE:

Minimal hepatic encephalopathy

HE:

Hepatic encephalopathy

TRB:

Trails B test

DSST:

Digit symbol substitution test

WCC:

White cell count

CRP:

C-reactive protein

IL-6:

Interleukin 6

NOx :

Nitrate/nitrite

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Acknowledgement

We thank all the members of the Liver Failure Group and our collaborators for their helpful advice and discussion.

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Authors and Affiliations

  1. Liver Failure Group, The UCL Institute of Hepatology, Division of Medicine, University College London, 69–75 Chenies Mews, London, WC1E 6HX, UK

    D. L. Shawcross, G. Wright, S. W. M. Olde Damink & R. Jalan

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  1. D. L. Shawcross
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  2. G. Wright
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  3. S. W. M. Olde Damink
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  4. R. Jalan
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Correspondence to R. Jalan.

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Shawcross, D.L., Wright, G., Olde Damink, S.W.M. et al. Role of ammonia and inflammation in minimal hepatic encephalopathy. Metab Brain Dis 22, 125–138 (2007). https://doi.org/10.1007/s11011-006-9042-1

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