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COVID-19 in liver transplant candidates: pretransplant and post-transplant outcomes - an ELITA/ELTR multicentre cohort study
  1. Luca Saverio Belli1,
  2. Christophe Duvoux2,
  3. Paolo Angelo Cortesi3,
  4. Rita Facchetti3,
  5. Speranta Iacob4,
  6. Giovanni Perricone5,
  7. Sylvie Radenne6,
  8. Sara Conti7,
  9. Damiano Patrono8,
  10. Gabriela Berlakovich9,
  11. Angus Hann10,
  12. Luisa Pasulo11,
  13. Lluis Castells12,
  14. Francois Faitot13,
  15. Olivier Detry14,
  16. Federica Invernizzi15,
  17. Giulia Magini16,
  18. Paolo De Simone17,
  19. Ilias Kounis18,
  20. Maria Cristina Morelli19,
  21. Fernando Díaz Fontenla20,
  22. Bo-Göran Ericzon21,
  23. Carmelo Loinaz22,
  24. Chris Johnston23,
  25. Liliana Gheorghe24,
  26. Mickael Lesurtel25,
  27. Renato Romagnoli8,
  28. Dagmar Kollmann9,
  29. M Thamara PR Perera26,
  30. Stefano Fagiuoli27,
  31. Darius Mirza26,
  32. Audrey Coilly28,29,
  33. Christian Toso30,
  34. Krzysztof Zieniewicz31,
  35. Laure Elkrief32,
  36. Vincent Karam33,
  37. Rene Adam33,
  38. Caroline den Hoed34,
  39. Marco Merli35,
  40. Massimo Puoti35,
  41. Luciano De Carlis36,
  42. Gabriel C Oniscu21,
  43. Salvatore Piano37,
  44. Paolo Angeli37,
  45. Constantino Fondevila38,
  46. Wojciech G Polak39
  47. for all the centres contributing to the ELITA-ELTR COVID-19 Registry
    1. 1 Hepatology and Gastroenterology, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
    2. 2 Hepatology, Hopital Henri Mondor, Creteil, France
    3. 3 Research Centre on Public Health (CESP), Universita degli Studi di Milano-Bicocca Scuola di Medicina e Chirurgia, Monza, Italy
    4. 4 Digestive Diseases and Liver Transplantation Center, Institutul Clinic Fundeni, Bucharest, Romania
    5. 5 Epatologia e Gastroenterologia, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
    6. 6 Service Hépatologie et Gastro-Entérologie, Hospital Croix-Rousse, Lyon, France
    7. 7 Research Centre on Public Health (CESP), Università degli Studi di Milano-Bicocca, Milano, Italy
    8. 8 Liver Transplantation Unit, Ospedale Molinette, Torino, Italy
    9. 9 Division of Transplantation, Department of General Surgery, Medical University of Vienna, Vienna, Austria
    10. 10 Department of Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, UK
    11. 11 Gastroenterology and Transplant Hepatology, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
    12. 12 Liver Transplant Unit, HPB Surgery and Transplants, Hospital Vall d'Hebron, Barcelona, Spain
    13. 13 Service de Chirurgie Hepatobiliare and Transplantation, Hôpital de Hautepierre, Strasbourg, France
    14. 14 Department of Abdominal Surgery and Transplantation, CHU Liege, University of Liege, Liege, Belgium
    15. 15 Division of Gastroenterology and Hepatology, Policlinico di Milano, Milan, Italy
    16. 16 Division of Abdominal Surgery, Department of Surgery, Geneva University Hospitals, Geneve, Switzerland
    17. 17 Trapiantologia Epatica Universitaria, Ospedale Cisanello, Pisa, Italy
    18. 18 Centre Hépatobiliaire, Hospital Paul Brousse, Villejuif, France
    19. 19 Department of Organ Failures and Transplantation, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
    20. 20 Liver Transplantation Unit, Hospital General Universitario Gregorio Maranon, Madrid, Spain
    21. 21 Transplantation Surgery, Karolinska Institute, Stockholm, Sweden
    22. 22 HBP and Transplant Unit, Hospital Universitario 12 de Octubre, Madrid, Spain
    23. 23 Liver Transplantation Unit, Edinburgh Royal Infirmary, Edinburgh, Edinburgh, UK
    24. 24 Digestive Diseases and Liver Transplantation Center, Clinical Institute Fundeni, Bucuresti, Romania
    25. 25 Department of Surgery and Transplanattion, Hospital Croix-Rousse, Lyon, Rhône-Alpes, France
    26. 26 Department of Surgery, Queen Elizabeth Hospital, Birmingham, Birmingham, UK
    27. 27 Department of Gastroenterology, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Lombardia, Italy
    28. 28 Centre Hépato-Biliaire, Hôpital Paul Brousse, Villejuif, Île-de-France, France
    29. 29 UMR-S1193, INSERM, Villejuif, Île-de-France, France
    30. 30 Department of Surgery, Geneva University Hospitals, Geneve, Switzerland
    31. 31 Department of General, Transplant and Liver Surgery, Faculty of Medicine, Medical University of Warsaw, Warszawa, Poland
    32. 32 Hepatogastroenterology Unit, Hopital Trousseau, Chambray-les-Tours, France
    33. 33 Centre Hépatobiliaire, Hôpital Paul Brousse, Villejuif, France
    34. 34 Gastroenterology and Hepatology, Rotterdam, The Netherlands
    35. 35 Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
    36. 36 Chirurgia Generale e dei Trapianti, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
    37. 37 Department of Medicine, Faculty of Medicine and Surgery, University of Padua, Padova, Italy
    38. 38 General and Digestive Surgery, Hospital Clinic de Barcelona, Barcelona, Spain
    39. 39 Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands
    1. Correspondence to Dr Luca Saverio Belli, Hepatology and Gastroenterology, ASST Grande Ospedale Metropolitano Niguarda, Milano, MI 20162, Italy; luca.belli{at}ospedaleniguarda.it

    Abstract

    Objective Explore the impact of COVID-19 on patients on the waiting list for liver transplantation (LT) and on their post-LT course.

    Design Data from consecutive adult LT candidates with COVID-19 were collected across Europe in a dedicated registry and were analysed.

    Results From 21 February to 20 November 2020, 136 adult cases with laboratory-confirmed SARS-CoV-2 infection from 33 centres in 11 European countries were collected, with 113 having COVID-19. Thirty-seven (37/113, 32.7%) patients died after a median of 18 (10–30) days, with respiratory failure being the major cause (33/37, 89.2%). The 60-day mortality risk did not significantly change between first (35.3%, 95% CI 23.9% to 50.0%) and second (26.0%, 95% CI 16.2% to 40.2%) waves. Multivariable Cox regression analysis showed Laboratory Model for End-stage Liver Disease (Lab-MELD) score of ≥15 (Model for End-stage Liver Disease (MELD) score 15–19, HR 5.46, 95% CI 1.81 to 16.50; MELD score≥20, HR 5.24, 95% CI 1.77 to 15.55) and dyspnoea on presentation (HR 3.89, 95% CI 2.02 to 7.51) being the two negative independent factors for mortality. Twenty-six patients underwent an LT after a median time of 78.5 (IQR 44–102) days, and 25 (96%) were alive after a median follow-up of 118 days (IQR 31–170).

    Conclusions Increased mortality in LT candidates with COVID-19 (32.7%), reaching 45% in those with decompensated cirrhosis (DC) and Lab-MELD score of ≥15, was observed, with no significant difference between first and second waves of the pandemic. Respiratory failure was the major cause of death. The dismal prognosis of patients with DC supports the adoption of strict preventative measures and the urgent testing of vaccination efficacy in this population. Prior SARS-CoV-2 symptomatic infection did not affect early post-transplant survival (96%).

    • liver cirrhosis
    • liver transplantation
    • COVID-19

    Data availability statement

    Data are available upon reasonable request. Contacts:Rita Facchetti, Rita.Facchetti@unimib.it; Paolo Cortesi, Paolo.cortesi@unimib.it; IDOTCOVID platform.

    This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

    https://bmj.com/coronavirus/usage

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    Data availability statement

    Data are available upon reasonable request. Contacts:Rita Facchetti, Rita.Facchetti@unimib.it; Paolo Cortesi, Paolo.cortesi@unimib.it; IDOTCOVID platform.

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    Footnotes

    • CF and WGP are joint senior authors.

    • LSB, CD and PAC are joint first authors.

    • Twitter @NONE

    • Collaborators Raffaella Viganò, Chiara Mazzarelli, Andrea Lauterio, Alessandro Giacomoni, Giovanna Travi, Massimo Puoti, Francesca Donato, Pietro Lampertico, Michele Colledan, Marco Zambelli, Michela Guizzetti, Giovanni Vitale, Fabrizio Di Benedetto, Paola Carrai, Stefania Petruccelli,Simone Incicco, Nicola Zen, Baptiste Michard, Saliba Faouzi, Didier Samiuel, Norbert Ngongang, Domitille Poinsot, Celine Guichon, Emmanuel Gonzales, Gabriel Oniscu, Derek Manaz, Jordi Colmenero, David Toapanta, Ernest Hidalgo, Jose Maria Alamo,Esther Brea Gomes, Gerardo Blanco, Alberto Marcacuzco, Gonzalo Rodriguez, Sonia Pascual, Georg Györi, JAcques Pirenne, Natalie Vandende, Valerio Lucidi, Giulia Magini, Nicolas Goossens, Carl Jorns, Irinel Popescu and Joanna Raszeja-Wyszomirska.

    • Contributors LSB: conceptualisation, data curation and drafting and critical revision of the manuscript; RF, PAC and SC: formal analysis and critical revision of the manuscript; CF, WGP, CD and GP: conceptualisation, review and editing, and critical revision of the manuscript; SR, DP, GB, AH, LP, LC, FF, OD, FI, GM, PDS, IK, MCM, FDF, B-GE, CL, CJ, LG, ML, RR, DK, MTPRP, SF, DM, AC, CT, KZ, LE, VK, RA, CdH, MM, MP, LDC, SP, GO and PA: data curation and critical revision of the manuscript; SF and LDC: critical revision of the manuscript.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.