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Reply to: “Ammonia - an old friend with a new area of application”

  • Author Footnotes
    † Joint first authors
    Thomas H. Tranah
    Footnotes
    † Joint first authors
    Affiliations
    Institute of Liver Studies, Dept of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King´s College London, London, United Kingdom
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  • Author Footnotes
    † Joint first authors
    María-Pilar Ballester
    Footnotes
    † Joint first authors
    Affiliations
    Digestive Disease Department, Hospital Clínico Universitario de Valencia, Spain

    INCLIVA Biomedical Research Institute, Valencia, Spain
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  • Author Footnotes
    † Joint first authors
    Juan Antonio Carbonell-Asins
    Footnotes
    † Joint first authors
    Affiliations
    INCLIVA Biomedical Research Institute, Valencia, Spain
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  • Author Footnotes
    ‡ Joint senior authors
    Rajiv Jalan
    Correspondence
    Corresponding author. Address: Liver Failure Group, Institute for Liver and Disease Health, University College London, Royal Free Campus. Rowland Hill Street, London, NW3 2PF, United Kingdom. Tel.: +44 02074332795.
    Footnotes
    ‡ Joint senior authors
    Affiliations
    Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Campus, United Kingdom

    European Foundation for the Study of Chronic Liver Failure (EF Clif), Spain
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  • Author Footnotes
    ‡ Joint senior authors
    Debbie L. Shawcross
    Footnotes
    ‡ Joint senior authors
    Affiliations
    Institute of Liver Studies, Dept of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King´s College London, London, United Kingdom
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  • Author Footnotes
    † Joint first authors
    ‡ Joint senior authors
Published:October 07, 2022DOI:https://doi.org/10.1016/j.jhep.2022.09.023
      We are very appreciative of the interest garnered by our recently published article and were pleased to receive further validating data from Gairing et al. in response to our findings.
      • Gairing S.J.
      • Kaps L.
      • Schleicher E.M.
      • Galle P.R.
      • Labenz C.
      Ammonia - an old friend with a new area of application.
      ,
      • Tranah T.H.
      • Ballester M.P.
      • Carbonell-Asins J.A.
      • Ampuero J.
      • Alexandrino G.
      • Caracostea A.
      • et al.
      Plasma ammonia levels predict hospitalisation with liver-related complications and mortality in clinically stable outpatients with cirrhosis.
      In our manuscript, we demonstrated that ammonia levels, expressed as a ratio of the local laboratory upper limit of normal (AMM-ULN) is an independent predictor of hospitalisation with liver-related complications and mortality in stable outpatients with cirrhosis and that an AMM-ULN cut-off value of 1.4 defines the risk of liver-related complications and consequent mortality. In order to address overfitting, we collected data from three independent units for utilisation in our training and test models and furthermore validated findings in an external cohort of 130 individuals, demonstrating the validity of AMM-ULN as a marker of adverse outcomes.

      Linked Article

      • Plasma ammonia levels predict hospitalisation with liver-related complications and mortality in clinically stable outpatients with cirrhosis
        Journal of HepatologyVol. 77Issue 6
        • Preview
          Hyperammonaemia is central in the pathogenesis of hepatic encephalopathy. It also has pleiotropic deleterious effects on several organ systems, such as immune function, sarcopenia, energy metabolism and portal hypertension. This study was performed to test the hypothesis that severity of hyperammonaemia is a risk factor for liver-related complications in clinically stable outpatients with cirrhosis.
        • Full-Text
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        Open Access
      • Ammonia - an old friend with a new area of application
        Journal of HepatologyVol. 78Issue 1
        • Preview
          We read with great interest the article by Tranah et al. recently published in the Journal of Hepatology.1 Ammonia is known to play a key role in the pathophysiology of hepatic encephalopathy. Recent evidence has also indicated the pathophysiological role and the value of measuring ammonia even in hospitalized patients with acute decompensation.2 In their current multicenter study, Tranah et al. evaluated the predictive value of ammonia in outpatients with cirrhosis regarding liver-related hospitalizations and mortality.
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      References

        • Gairing S.J.
        • Kaps L.
        • Schleicher E.M.
        • Galle P.R.
        • Labenz C.
        Ammonia - an old friend with a new area of application.
        J Hepatol. 2023; 78: e22-e23
        • Tranah T.H.
        • Ballester M.P.
        • Carbonell-Asins J.A.
        • Ampuero J.
        • Alexandrino G.
        • Caracostea A.
        • et al.
        Plasma ammonia levels predict hospitalisation with liver-related complications and mortality in clinically stable outpatients with cirrhosis.
        J Hepatol. 2022; 77: 1554-1563
        • Gairing S.J.
        • Anders J.
        • Kaps L.
        • Nagel M.
        • Michel M.
        • Kremer W.M.
        • et al.
        Evaluation of IL-6 for stepwise diagnosis of minimal hepatic encephalopathy in patients with liver cirrhosis.
        Hepatol Commun. 2022; 6: 1113-1122