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Non-invasive tests for clinically significant portal hypertension after HCV cure

  • Author Footnotes
    † G.S. and S.L. contributed equally to the work.
    Georg Semmler
    Footnotes
    † G.S. and S.L. contributed equally to the work.
    Affiliations
    Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria

    Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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  • Author Footnotes
    † G.S. and S.L. contributed equally to the work.
    Sabela Lens
    Footnotes
    † G.S. and S.L. contributed equally to the work.
    Affiliations
    Liver Unit, Hospital Clínic, Universitat de Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Spain

    August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Universitat de Barcelona, Barcelona, Spain

    Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain
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  • Elias L. Meyer
    Affiliations
    Institute for Medical Statistics, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University Vienna, Vienna, Austria
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  • Anna Baiges
    Affiliations
    Liver Unit, Hospital Clínic, Universitat de Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Spain

    August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Universitat de Barcelona, Barcelona, Spain

    Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain
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  • Edilmar Alvardo-Tapias
    Affiliations
    Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain

    Hospital of Santa Creu and Sant Pau, Autonomous University of Barcelona, Hospital Sant Pau Biomedical Research Institute (IIB Sant Pau), Barcelona, Spain
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  • Elba Llop
    Affiliations
    Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain

    Liver Unit, Hospital Universitario Puerta De Hierro Majadahonda, Universidad Autònoma de Madrid, Madrid, Spain
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  • Luis Tellez
    Affiliations
    Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, IRYCIS, University of Alcalá, Madrid, Spain
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  • Philipp Schwabl
    Affiliations
    Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria

    Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria

    UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, United Kingdom
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  • Ezequiel Mauro
    Affiliations
    Liver Unit and Liver Transplant Unit, Hospital Italiano, Buenos Aires, Argentina
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  • Laia Escudé
    Affiliations
    Liver Unit, Hospital Clínic, Universitat de Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Spain

    August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Universitat de Barcelona, Barcelona, Spain

    Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain
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  • Cristina Díez
    Affiliations
    Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario Gregorio Marañón, Madrid, Spain

    Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
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  • Luis Ibañez-Samaniego
    Affiliations
    Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain

    Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario Gregorio Marañón, Madrid, Spain

    Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
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  • Ángela Puente
    Affiliations
    Servicio de Aparato Digestivo, Hospital Universitario Marqués de Valdecilla, Santander, Spain
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  • José Ignacio Fortea
    Affiliations
    Servicio de Aparato Digestivo, Hospital Universitario Marqués de Valdecilla, Santander, Spain
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  • Marta Abadía
    Affiliations
    Servicio de Aparato Digestivo, Hospital Universitario La Paz, Madrid, Spain
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  • Alberto Zanetto
    Affiliations
    Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padua University Hospital, Padua, Italy
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  • Andrés Conthe
    Affiliations
    Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain

    Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
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  • Helena Hernandez-Évole
    Affiliations
    Liver Unit, Hospital Clínic, Universitat de Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Spain

    August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
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  • Irina Sofia Luzko Scheid
    Affiliations
    Liver Unit, Hospital Clínic, Universitat de Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Spain

    August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
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  • Jidong Jia
    Affiliations
    Liver Research Center, Beijing Friendship Hospital, Capital Medial University, Beijing, China

    Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, Beijing, China

    National Clinical Research Center for Digestive Diseases, Beijing, China
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  • Hitoshi Yoshiji
    Affiliations
    Department of Gastroenterology, Nara Medical University, Nara, Japan
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  • Sven M. Francque
    Affiliations
    Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium

    Laboratory of Experimental Medicine and Paediatrics (LEMP), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium

    InflaMed Centre of Excellence, University of Antwerp, Antwerp, Belgium

    Translational Sciences in Inflammation and Immunology, University of Antwerp, Antwerp, Belgium
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  • Emmanuel A. Tsochatzis
    Affiliations
    UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, United Kingdom

    Sheila Sherlock Liver Centre, Royal Free Hospital, London, United Kingdom
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  • Francesco Paolo Russo
    Affiliations
    Servicio de Aparato Digestivo, Hospital Universitario La Paz, Madrid, Spain
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  • Gonzalo Crespo
    Affiliations
    Liver Unit, Hospital Clínic, Universitat de Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Spain

    August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Universitat de Barcelona, Barcelona, Spain

    Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain
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  • Xavier Forns
    Affiliations
    Liver Unit, Hospital Clínic, Universitat de Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Spain

    August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Universitat de Barcelona, Barcelona, Spain

    Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain
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  • Rafael Bañares
    Affiliations
    Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario Gregorio Marañón, Madrid, Spain

    Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain

    Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain

    Universidad Complutense de Madrid, Madrid, Spain
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  • Càndid Villanueva
    Affiliations
    Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain

    Hospital of Santa Creu and Sant Pau, Autonomous University of Barcelona, Hospital Sant Pau Biomedical Research Institute (IIB Sant Pau), Barcelona, Spain
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  • Virginia Hernández-Gea
    Affiliations
    Liver Unit, Hospital Clínic, Universitat de Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Spain

    August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Universitat de Barcelona, Barcelona, Spain

    Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain
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  • Thomas Reiberger
    Affiliations
    Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria

    Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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  • Jaume Bosch
    Affiliations
    Liver Unit, Hospital Clínic, Universitat de Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Spain

    August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Universitat de Barcelona, Barcelona, Spain

    Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain

    Department of Visceral Surgery and Medicine, Inselspital, University of Bern, Bern, Switzerland
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  • Author Footnotes
    ‡ J.C.G-P. and M.M. share the corresponding and last author position.
    Juan Carlos García Pagán
    Correspondence
    Corresponding authors. Address: Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Clínic, Carrer de Villaroel, 170, 08036 Barcelona, Spain; Tel.: +34 932275790, fax: +34 932279856.
    Footnotes
    ‡ J.C.G-P. and M.M. share the corresponding and last author position.
    Affiliations
    Liver Unit, Hospital Clínic, Universitat de Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Spain

    August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Universitat de Barcelona, Barcelona, Spain

    Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain
    Search for articles by this author
  • Author Footnotes
    ‡ J.C.G-P. and M.M. share the corresponding and last author position.
    Mattias Mandorfer
    Correspondence
    Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria; Tel.: +43 1 40400 47440, fax: +43 1 40400 47350.
    Footnotes
    ‡ J.C.G-P. and M.M. share the corresponding and last author position.
    Affiliations
    Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria

    Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
    Search for articles by this author
  • A study by the Baveno Cooperation: an EASL consortium
  • Author Footnotes
    † G.S. and S.L. contributed equally to the work.
    ‡ J.C.G-P. and M.M. share the corresponding and last author position.
Published:September 02, 2022DOI:https://doi.org/10.1016/j.jhep.2022.08.025

      Highlights

      • Post-treatment LSM/platelet count can be used to estimate the probability of CSPH and predict clinical outcomes in cACLD.
      • Patients with cACLD and LSM <12 kPa & PLT >150 G/L (CSPH-excluded; no decompensation risk) may not require portal hypertension surveillance.
      • Patients with cACLD and LSM ≥25 kPa require surveillance/treatment (CSPH-ruled-in; increased decompensation risk).

      Background & Aims

      Non-invasive tests (NITs) for clinically significant portal hypertension (CSPH; hepatic venous pressure gradient [HVPG] ≥10 mmHg) have predominantly been studied in patients with active HCV infection. Investigations after HCV cure are limited and have yielded conflicting results. We conducted a pooled analysis to determine the diagnostic/prognostic utility of liver stiffness measurement (LSM)/platelet count (PLT) in this setting.

      Methods

      A total of 418 patients with pre-treatment HVPG ≥6 mmHg who achieved sustained virological response (SVR) and underwent post-treatment HVPG measurement were assessed, of whom 324 (HVPG/NIT-cohort) also had paired data on pre-/post-treatment LSM/PLT. The derived LSM/PLT criteria were then validated against the direct endpoint decompensation in 755 patients with compensated advanced chronic liver disease (cACLD) with SVR (cACLD-validation-cohort).

      Results

      HVPG/NIT-cohort: Among patients with cACLD, the pre-/post-treatment prevalence of CSPH was 80%/54%. The correlation between LSM/HVPG increased from pre- to post-treatment (r = 0.45 vs. 0.60), while that of PLT/HVPG remained unchanged. For given LSM/PLT values, HVPG tended to be lower post- vs. pre-treatment, indicating the need for dedicated algorithms. Combining post-treatment LSM/PLT yielded a high diagnostic accuracy for post-treatment CSPH in cACLD (AUC 0.884; 95% CI 0.843–0.926). Post-treatment LSM <12 kPa & PLT >150 G/L excluded CSPH (sensitivity: 99.2%), while LSM ≥25 kPa was highly specific for CSPH (93.6%). cACLD-validation-cohort: the 3-year decompensation risk was 0% in the 42.5% of patients who met the LSM <12 kPa & PLT >150 G/L criteria. In patients with post-treatment LSM ≥25 kPa (prevalence: 16.8%), the 3-year decompensation risk was 9.6%, while it was 1.3% in those meeting none of the above criteria (prevalence: 40.7%).

      Conclusions

      NITs can estimate the probability of CSPH after HCV cure and predict clinical outcomes. Patients with cACLD but LSM <12 kPa & PLT>150 G/L may be discharged from portal hypertension surveillance if no co-factors are present, while patients with LSM ≥25 kPa require surveillance/treatment.

      Lay summary

      Measurement of liver stiffness by a specific ultrasound device and platelet count (a simple blood test) are broadly used for the non-invasive diagnosis of increased blood pressure in the veins leading to the liver, which drives the development of complications in patients with advanced liver disease. The results of our pooled analysis refute previous concerns that these tests are less accurate after the cure of hepatitis C virus (HCV) infection. We have developed diagnostic criteria that facilitate personalized management after HCV cure and allow for a de-escalation of care in a high proportion of patients, thereby decreasing disease burden.

      Graphical abstract

      Keywords

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