Serological response and breakthrough infection after COVID-19 vaccination in patients with cirrhosis and post-liver transplant.


Journal

Hepatology communications
ISSN: 2471-254X
Titre abrégé: Hepatol Commun
Pays: United States
ID NLM: 101695860

Informations de publication

Date de publication:
01 11 2023
Historique:
received: 14 03 2023
accepted: 21 06 2023
medline: 30 10 2023
pubmed: 23 10 2023
entrez: 23 10 2023
Statut: epublish

Résumé

Vaccine hesitancy and lack of access remain major issues in disseminating COVID-19 vaccination to liver patients globally. Factors predicting poor response to vaccination and risk of breakthrough infection are important data to target booster vaccine programs. The primary aim of the current study was to measure humoral responses to 2 doses of COVID-19 vaccine. Secondary aims included the determination of factors predicting breakthrough infection. COVID-19 vaccination and Biomarkers in cirrhosis And post-Liver Transplantation is a prospective, multicenter, observational case-control study. Participants were recruited at 4-10 weeks following first and second vaccine doses in cirrhosis [n = 325; 94% messenger RNA (mRNA) and 6% viral vaccine], autoimmune liver disease (AILD) (n = 120; 77% mRNA and 23% viral vaccine), post-liver transplant (LT) (n = 146; 96% mRNA and 3% viral vaccine), and healthy controls (n = 51; 72% mRNA, 24% viral and 4% heterologous combination). Serological end points were measured, and data regarding breakthrough SARS-CoV-2 infection were collected. After adjusting by age, sex, and time of sample collection, anti-Spike IgG levels were the lowest in post-LT patients compared to cirrhosis (p < 0.0001), AILD (p < 0.0001), and control (p = 0.002). Factors predicting reduced responses included older age, Child-Turcotte-Pugh B/C, and elevated IL-6 in cirrhosis; non-mRNA vaccine in AILD; and coronary artery disease, use of mycophenolate and dysregulated B-call activating factor, and lymphotoxin-α levels in LT. Incident infection occurred in 6.6%, 10.6%, 7.4%, and 15.6% of cirrhosis, AILD, post-LT, and control, respectively. The only independent factor predicting infection in cirrhosis was low albumin level. LT patients present the lowest response to the SARS-CoV-2 vaccine. In cirrhosis, the reduced response is associated with older age, stage of liver disease and systemic inflammation, and breakthrough infection with low albumin level.

Sections du résumé

BACKGROUND
Vaccine hesitancy and lack of access remain major issues in disseminating COVID-19 vaccination to liver patients globally. Factors predicting poor response to vaccination and risk of breakthrough infection are important data to target booster vaccine programs. The primary aim of the current study was to measure humoral responses to 2 doses of COVID-19 vaccine. Secondary aims included the determination of factors predicting breakthrough infection.
METHODS
COVID-19 vaccination and Biomarkers in cirrhosis And post-Liver Transplantation is a prospective, multicenter, observational case-control study. Participants were recruited at 4-10 weeks following first and second vaccine doses in cirrhosis [n = 325; 94% messenger RNA (mRNA) and 6% viral vaccine], autoimmune liver disease (AILD) (n = 120; 77% mRNA and 23% viral vaccine), post-liver transplant (LT) (n = 146; 96% mRNA and 3% viral vaccine), and healthy controls (n = 51; 72% mRNA, 24% viral and 4% heterologous combination). Serological end points were measured, and data regarding breakthrough SARS-CoV-2 infection were collected.
RESULTS
After adjusting by age, sex, and time of sample collection, anti-Spike IgG levels were the lowest in post-LT patients compared to cirrhosis (p < 0.0001), AILD (p < 0.0001), and control (p = 0.002). Factors predicting reduced responses included older age, Child-Turcotte-Pugh B/C, and elevated IL-6 in cirrhosis; non-mRNA vaccine in AILD; and coronary artery disease, use of mycophenolate and dysregulated B-call activating factor, and lymphotoxin-α levels in LT. Incident infection occurred in 6.6%, 10.6%, 7.4%, and 15.6% of cirrhosis, AILD, post-LT, and control, respectively. The only independent factor predicting infection in cirrhosis was low albumin level.
CONCLUSIONS
LT patients present the lowest response to the SARS-CoV-2 vaccine. In cirrhosis, the reduced response is associated with older age, stage of liver disease and systemic inflammation, and breakthrough infection with low albumin level.

Identifiants

pubmed: 37870985
doi: 10.1097/HC9.0000000000000273
pii: 02009842-202311010-00008
pmc: PMC10586829
pii:
doi:

Substances chimiques

Albumins 0
COVID-19 Vaccines 0
RNA, Messenger 0
Viral Vaccines 0

Types de publication

Journal Article Multicenter Study Observational Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.

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Auteurs

Gautam Mehta (G)

Institute for Liver and Digestive Heath, University College London, London, UK.
The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK.
Royal Free London NHS Foundation Trust, London, UK.

Antonio Riva (A)

The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK.
Faculty of Life Sciences and Medicine, King's College London, London, UK.

Maria Pilar Ballester (MP)

Department of Gastroenterology and Hepatology, Hospital Clínico Universitario de Valencia, Valencia, Spain.

Eva Uson (E)

European Foundation for the Study of Chronic Liver Failure (EF CLIF), EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain.

Montserrat Pujadas (M)

European Foundation for the Study of Chronic Liver Failure (EF CLIF), EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain.

Ângela Carvalho-Gomes (Â)

Hepatology, HBP Surgery and Transplantation, Hepatology & Liver Transplant Unit, La Fe University Hospital, Valencia, Spain.
Ciberehd, Universidad de Valencia, Valencia, Spain.

Ivan Sahuco (I)

Hepatology, HBP Surgery and Transplantation, Hepatology & Liver Transplant Unit, La Fe University Hospital, Valencia, Spain.
Ciberehd, Universidad de Valencia, Valencia, Spain.

Ariadna Bono (A)

Hepatology, HBP Surgery and Transplantation, Hepatology & Liver Transplant Unit, La Fe University Hospital, Valencia, Spain.
Ciberehd, Universidad de Valencia, Valencia, Spain.

Federico D'Amico (F)

ASST Grande Ospedale Metropolitano Niguarda, Infectious Diseases Unit, Milan, Italy.
Department of Medical Biotechnology and Translational Medicine, Postgraduate School of Clinical Pharmacology and Toxicology, University of Milan, Milan, Italy.

Raffaela Viganò (R)

ASST Grande Ospedale Metropolitano Niguarda, Hepatology and Gastroenterology Unit, Milan, Italy.

Elena Diago (E)

Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro Majadahonda, IDIPHIM, Madrid, Spain.
Central Unit of Clinical Research and Clinical Trials, Hospital Universitario La Paz, IdiPaz, Madrid, Spain.
CIBERehd, Madrid, Spain.

Beatriz Tormo Lanseros (BT)

Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro Majadahonda, IDIPHIM, Madrid, Spain.
CIBERehd, Madrid, Spain.

Elvira Inglese (E)

ASST Grande Ospedale Metropolitano Niguarda, Hepatology and Gastroenterology Unit, Milan, Italy.
Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.

Dani Martinez Vazquez (DM)

Liver Unit, Hospital Universitario Valle de Hebron, Barcelona, Spain.

Rajni Sharma (R)

The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK.

Hio Lam Phoebe Tsou (HLP)

The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK.

Nicola Harris (N)

The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK.

Annelotte Broekhoven (A)

Department of Gastroenterology and Hepatology, Leiden University Medical Center, RC Leiden, the Netherlands.

Marjolein Kikkert (M)

Department of Medical Microbiology, Leiden University Medical Center, RC Leiden, the Netherlands.

Shessy P Torres Morales (SPT)

Department of Medical Microbiology, Leiden University Medical Center, RC Leiden, the Netherlands.

Sebenzile K Myeni (SK)

Department of Medical Microbiology, Leiden University Medical Center, RC Leiden, the Netherlands.

Mar Riveiro-Barciela (M)

Liver Unit, Hospital Universitario Valle de Hebron, Barcelona, Spain.

Adriana Palom (A)

Liver Unit, Hospital Universitario Valle de Hebron, Barcelona, Spain.

Nicola Zeni (N)

Department of Medicine - DIMED, Unit of Internal Medicine and Hepatology (UIMH), University of Padova, Padova, Italy.

Alessandra Brocca (A)

Department of Medicine - DIMED, Unit of Internal Medicine and Hepatology (UIMH), University of Padova, Padova, Italy.

Annarosa Cussigh (A)

Hepatology and Liver Transplantation Unit, Azienda Sanitaria Universitaria Integrata, University of Udine, Udine, Italy.

Sara Cmet (S)

Hepatology and Liver Transplantation Unit, Azienda Sanitaria Universitaria Integrata, University of Udine, Udine, Italy.

Desamparados Escudero-García (D)

Department of Gastroenterology and Hepatology, Hospital Clínico Universitario de Valencia, Valencia, Spain.

Matteo Stocco (M)

Department of Gastroenterology and Hepatology, Hospital Clínico Universitario de Valencia, Valencia, Spain.

Leonardo Antonio Natola (LA)

Azienda Ospedaiera Universitaria Integrata Verona, Verona Italy.

Donatella Ieluzzi (D)

Azienda Ospedaiera Universitaria Integrata Verona, Verona Italy.

Veronica Paon (V)

Azienda Ospedaiera Universitaria Integrata Verona, Verona Italy.

Angelo Sangiovanni (A)

Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy.

Elisa Farina (E)

Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy.

Clara di Benedetto (C)

Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy.

Yolanda Sánchez-Torrijos (Y)

Hospital Universitario Virgen del Rocio, Sevilla. Instituto de Biomedicina de Sevilla, Universidad de Sevilla, Sevilla, Spain.

Ana Lucena-Varela (A)

Hospital Universitario Virgen del Rocio, Sevilla. Instituto de Biomedicina de Sevilla, Universidad de Sevilla, Sevilla, Spain.

Eva Román (E)

Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
EUI-Sant Pau School of Nursing, Barcelona, Spain.

Elisabet Sánchez (E)

CIBERehd, Madrid, Spain.
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

Rubén Sánchez-Aldehuelo (R)

Servicio de Gastroenterología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto Salud Carlos III, Madrid, Spain.
Universidad de Alcalá, Madrid, Spain.

Julia López-Cardona (J)

Servicio de Gastroenterología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto Salud Carlos III, Madrid, Spain.

Itzel Canas-Perez (I)

Royal Free London NHS Foundation Trust, London, UK.

Christine Eastgate (C)

Royal Free London NHS Foundation Trust, London, UK.

Dhaarica Jeyanesan (D)

Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK.

Alejandro Esquivel Morocho (AE)

Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK.

Simone Di Cola (S)

Department of Translational and Precision Medicine, University of Rome Sapienza, Roma, Italy.

Lucia Lapenna (L)

Department of Translational and Precision Medicine, University of Rome Sapienza, Roma, Italy.

Giacomo Zaccherini (G)

Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

Deborah Bongiovanni (D)

Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

Paola Zanaga (P)

Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
Gastroenterology and Multivisceral Transplant Units, Azienda Ospedale Università' di Padova, Padova, Italy.

Katia Sayaf (K)

Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
Gastroenterology and Multivisceral Transplant Units, Azienda Ospedale Università' di Padova, Padova, Italy.

Sabir Hossain (S)

Mid & South Essex NHS Foundation Trust, Basildon, UK.

Javier Crespo (J)

Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, Santander, Spain.
Clinical and Traslational Digestive Research Group, Instituto de Investigación Sanitaria Valdecilla (IDIVAL), Santander, Spain.

Mercedes Robles-Díaz (M)

CIBERehd, Madrid, Spain.
Servicio de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain.

Antonio Madejón (A)

Liver Unit, Hospital Universitario La Paz, CIBERehd, IdiPAZ, Universidad Autónoma de Madrid, Madrid, Spain.

Helena Degroote (H)

Department of Gastroenterology and Hepatology, Ghent University Hospital, Belgium.
Liver Research Center Ghent, Ghent University, Belgium.
European Reference Network (ERN)RARE-LIVER.

Javier Fernández (J)

European Foundation for the Study of Chronic Liver Failure (EF CLIF), EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain.
Liver Unit, Hospital Clínic, Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS) and Centro de Investigación Biomèdica en Red (CIBEREHD), Barcelona, Spain.

Marko Korenjak (M)

European Liver Patients' Association (ELPA).

Xavier Verhelst (X)

Department of Gastroenterology and Hepatology, Ghent University Hospital, Belgium.
Liver Research Center Ghent, Ghent University, Belgium.
European Reference Network (ERN)RARE-LIVER.

Javier García-Samaniego (J)

Liver Unit, Hospital Universitario La Paz, CIBERehd, IdiPAZ, Universidad Autónoma de Madrid, Madrid, Spain.

Raúl J Andrade (RJ)

CIBERehd, Madrid, Spain.
Servicio de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain.

Paula Iruzubieta (P)

Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, Santander, Spain.
Clinical and Traslational Digestive Research Group, Instituto de Investigación Sanitaria Valdecilla (IDIVAL), Santander, Spain.

Gavin Wright (G)

Mid & South Essex NHS Foundation Trust, Basildon, UK.

Paolo Caraceni (P)

Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Unit of Semeiotics, Liver and Alcohol-related Diseases, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Manuela Merli (M)

Department of Translational and Precision Medicine, University of Rome Sapienza, Roma, Italy.

Vishal C Patel (VC)

The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK.
Faculty of Life Sciences and Medicine, King's College London, London, UK.
Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK.

Amir Gander (A)

Royal Free London NHS Foundation Trust, London, UK.

Agustín Albillos (A)

Servicio de Gastroenterología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto Salud Carlos III, Madrid, Spain.

Germán Soriano (G)

CIBERehd, Madrid, Spain.
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

Maria Francesca Donato (MF)

Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy.

David Sacerdoti (D)

Azienda Ospedaiera Universitaria Integrata Verona, Verona Italy.

Pierluigi Toniutto (P)

Hepatology and Liver Transplantation Unit, Azienda Sanitaria Universitaria Integrata, University of Udine, Udine, Italy.

Maria Buti (M)

Liver Unit, Hospital Universitario Valle de Hebron, Barcelona, Spain.

Christophe Duvoux (C)

Department of Hepatogy-Liver Transplant Unit, Henri Mondor Hospital-APHP, Paris Est University, Paris, France.

Paolo Antonio Grossi (PA)

Department of Medicine and Surgery, University of Insubria, Infectious and Tropical Diseases Unit, ASST Sette Laghim, Varese, Italy.

Thomas Berg (T)

European Association for the Study of the Liver (EASL).

Wojciech G Polak (WG)

Department of Surgery, Division of HPB and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.

Massimo Puoti (M)

University of Milano Bicocca, Infectious Diseases Niguarda Great Metropolitan Hospital, Milan, Italy.

Anna Bosch-Comas (A)

European Foundation for the Study of Chronic Liver Failure (EF CLIF), EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain.

Luca Belli (L)

ASST Grande Ospedale Metropolitano Niguarda, Hepatology and Gastroenterology Unit, Milan, Italy.

Patrizia Burra (P)

Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
Gastroenterology and Multivisceral Transplant Units, Azienda Ospedale Università' di Padova, Padova, Italy.

Francesco Paolo Russo (FP)

Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
Gastroenterology and Multivisceral Transplant Units, Azienda Ospedale Università' di Padova, Padova, Italy.

Minneke Coenraad (M)

Department of Gastroenterology and Hepatology, Leiden University Medical Center, RC Leiden, the Netherlands.

José Luis Calleja (JL)

Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro Majadahonda, IDIPHIM, Madrid, Spain.
CIBERehd, Madrid, Spain.

Giovanni Perricone (G)

ASST Grande Ospedale Metropolitano Niguarda, Hepatology and Gastroenterology Unit, Milan, Italy.

Marina Berenguer (M)

Hepatology, HBP Surgery and Transplantation, Hepatology & Liver Transplant Unit, La Fe University Hospital, Valencia, Spain.
Ciberehd, Universidad de Valencia, Valencia, Spain.

Joan Claria (J)

European Foundation for the Study of Chronic Liver Failure (EF CLIF), EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain.
Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red (CIBERehd) and Universitat de Barcelona, Barcelona, Spain.

Richard Moreau (R)

European Foundation for the Study of Chronic Liver Failure (EF CLIF), EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain.
INSERM and Université Paris Cité, Centre de Recherche sur l'inflammation (CRI), Paris, France.
APHP, Service d'hépatologie, Hôpital Beaujon, Clichy, France.

Vicente Arroyo (V)

European Foundation for the Study of Chronic Liver Failure (EF CLIF), EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain.

Paolo Angeli (P)

Department of Medicine - DIMED, Unit of Internal Medicine and Hepatology (UIMH), University of Padova, Padova, Italy.

Cristina Sánchez (C)

European Foundation for the Study of Chronic Liver Failure (EF CLIF), EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain.

Javier Ampuero (J)

Hospital Universitario Virgen del Rocio, Sevilla. Instituto de Biomedicina de Sevilla, Universidad de Sevilla, Sevilla, Spain.

Salvatore Piano (S)

Department of Medicine - DIMED, Unit of Internal Medicine and Hepatology (UIMH), University of Padova, Padova, Italy.

Shilpa Chokshi (S)

The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK.
Faculty of Life Sciences and Medicine, King's College London, London, UK.

Rajiv Jalan (R)

Institute for Liver and Digestive Heath, University College London, London, UK.
Royal Free London NHS Foundation Trust, London, UK.

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