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Plasma copeptin as biomarker of disease progression and prognosis in cirrhosis

  • Author Footnotes
    † These authors contributed equally as joint first authors.
    Elsa Solà
    Correspondence
    Corresponding author. Address: Liver Unit, Hospital Clínic, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain. Tel.: +34932271713.
    Footnotes
    † These authors contributed equally as joint first authors.
    Affiliations
    Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain

    Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
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  • Author Footnotes
    † These authors contributed equally as joint first authors.
    Annarein J.C. Kerbert
    Footnotes
    † These authors contributed equally as joint first authors.
    Affiliations
    Department of Gastroenterology-Hepatology, Leiden University Medical Center, Leiden, The Netherlands
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  • Hein W. Verspaget
    Affiliations
    Department of Gastroenterology-Hepatology, Leiden University Medical Center, Leiden, The Netherlands
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  • Rebeca Moreira
    Affiliations
    Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain

    Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
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  • Elisa Pose
    Affiliations
    Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain

    Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
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  • Pablo Ruiz
    Affiliations
    Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain

    Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
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  • Raquel Cela
    Affiliations
    Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain

    Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
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  • Manuel Morales-Ruiz
    Affiliations
    Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain

    Biochemistry and Molecular Genetics Department, Hospital Clínic, University of Barcelona, Barcelona, Spain
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  • Eva López
    Affiliations
    Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain

    Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
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  • Isabel Graupera
    Affiliations
    Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain

    Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
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  • Cristina Solé
    Affiliations
    Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain

    Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
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  • Patricia Huelin
    Affiliations
    Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain

    Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
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  • Alex Amorós Navarro
    Affiliations
    EASL-CLIF Data Center, Barcelona, Spain
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  • Xavier Ariza
    Affiliations
    Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain

    Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
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  • Rajiv Jalan
    Affiliations
    Liver Failure Group, UCL Institute of Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, United Kingdom
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  • Núria Fabrellas
    Affiliations
    Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    School of Nursing, University of Barcelona, Spain
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  • Daniel Benten
    Affiliations
    Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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  • Gloria de Prada
    Affiliations
    Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain

    Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
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  • François Durand
    Affiliations
    Hepatology and Liver Intensive Care Unit, Hospital Beaujon, Clichy, France
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  • Wladimiro Jimenez
    Affiliations
    Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain

    Biochemistry and Molecular Genetics Department, Hospital Clínic, University of Barcelona, Barcelona, Spain
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  • Johan J. van der Reijden
    Affiliations
    Department of Gastroenterology-Hepatology, Leiden University Medical Center, Leiden, The Netherlands
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  • Javier Fernandez
    Affiliations
    Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain

    Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
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  • Bart van Hoek
    Affiliations
    Department of Gastroenterology-Hepatology, Leiden University Medical Center, Leiden, The Netherlands
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  • Author Footnotes
    ‡ These authors share senior authorship.
    Minneke J. Coenraad
    Footnotes
    ‡ These authors share senior authorship.
    Affiliations
    Department of Gastroenterology-Hepatology, Leiden University Medical Center, Leiden, The Netherlands
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  • Author Footnotes
    ‡ These authors share senior authorship.
    Pere Ginès
    Footnotes
    ‡ These authors share senior authorship.
    Affiliations
    Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain

    Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
    Search for articles by this author
  • Author Footnotes
    † These authors contributed equally as joint first authors.
    ‡ These authors share senior authorship.

      Background & Aims

      Research on vasopressin (AVP) in cirrhosis and its role in the assessment of prognosis has been hindered by the difficulty of measuring AVP levels accurately. Copeptin, a 39-aminoacid glycopeptide, is released from the neurohypophysis together with AVP. Copeptin could have a role as biomarker of prognosis in cirrhosis as it may reflect circulatory dysfunction. The aim of this study is to investigate the role of copeptin as biomarker of disease progression and prognosis in cirrhosis.

      Methods

      This prospective study is divided in 2 study protocols including 321 consecutive patients. Plasma copeptin levels were measured in all patients at study inclusion. Protocol 1: to investigate the relationship of copeptin with kidney and circulatory function (56 patients). Protocol 2: to investigate the relationship between copeptin and prognosis, as assessed by the development of complications of cirrhosis or mortality at 3 months (265 patients admitted to hospital for complications of cirrhosis).

      Results

      Patients with decompensated cirrhosis showed significantly higher plasma copeptin levels compared to those of patients with compensated cirrhosis. Copeptin levels had a significant positive correlation with model for end-satge liver disease (MELD) score, AVP, endogenous vasoconstrictor systems, and kidney function parameters. Patients developing complications of cirrhosis or mortality had significantly higher plasma copeptin levels compared to those of the remaining patients. Plasma copeptin levels were an independent predictive factor of both the development of complications and mortality at 3 months. This was confirmed in a validation series of 120 patients.

      Conclusions

      Copeptin is a novel biomarker of disease progression and prognosis in cirrhosis.

      Lay summary

      Copeptin is a fragment of the vasopressin precursor, a hormone that is known to be increased in patients with cirrhosis and that plays a role in the development of complications of the disease. Vasopressin is difficult to measure, but copeptin is a more stable molecule and is easier to measure in blood. Solà and Kerbert and colleagues have shown in a series of 361 patients that copeptin is markedly increased in patients with cirrhosis who develop complications during the following 3 months, compared to those patients who do not develop complications. Moreover, copeptin correlates with prognosis.

      Graphical abstract

      Keywords

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      Linked Article

      • Reply to: “Are we still searching for the fifth element of MELD?”
        Journal of HepatologyVol. 66Issue 1
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          We would like to thank the authors for their interest in our study. Overall, our study was not aimed at looking for a fifth element of MELD score but investigating the role of copeptin as biomarker of circulatory dysfunction, disease progression, and prognosis in cirrhosis. The main finding our study was that copeptin was not only an independent predictive factor of mortality but also of acute decompensation during a 3-month follow-up period. Moreover, the study showed that copeptin, as a good surrogate marker of vasopressin (AVP), likely reflected the progressive impairment of circulatory function of patients with decompensated cirrhosis [1].
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      • Are we still searching for the fifth element of MELD?
        Journal of HepatologyVol. 66Issue 1
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          We read with great interest the manuscript by Solà and colleagues [1]. The authors performed a single-center prospective study and evaluated, firstly, the relationship between copeptin and circulatory impairment in 56 cirrhotic patients and, secondly, the predictive value of copeptin on disease progression (i.e., occurrence or worsening of ascites, hepatic encephalopathy, gastrointestinal bleeding, hyponatremia, renal failure and bacterial infections) and on 3-month survival in 265 cirrhotic patients with varying degrees of severity, as shown by the wide range of model for end-stage liver disease (MELD) scores (7 to 40).
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