Epidemiological pattern, incidence, and outcomes of COVID-19 in liver transplant patients.


Journal

Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886

Informations de publication

Date de publication:
01 2021
Historique:
received: 08 05 2020
revised: 23 07 2020
accepted: 27 07 2020
pubmed: 5 8 2020
medline: 30 12 2020
entrez: 5 8 2020
Statut: ppublish

Résumé

The incidence and outcomes of coronavirus disease 2019 (COVID-19) in immunocompromised patients are a matter of debate. We performed a prospective nationwide study including a consecutive cohort of liver transplant patients with COVID-19 recruited during the Spanish outbreak from 28 February to 7 April, 2020. The primary outcome was severe COVID-19, defined as the need for mechanical ventilation, intensive care, and/or death. Age- and gender-standardised incidence and mortality ratios (SIR and SMR) were calculated using data from the Ministry of Health and the Spanish liver transplant registry. Independent predictors of severe COVID-19 among hospitalised patients were analysed using multivariate Cox regression. A total of 111 liver transplant patients were diagnosed with COVID-19 (SIR = 191.2 [95% CI 190.3-192.2]). The epidemiological curve and geographic distribution overlapped widely between the liver transplant and general populations. After a median follow-up of 23 days, 96 patients (86.5%) were admitted to hospital and 22 patients (19.8%) required respiratory support. A total of 12 patients were admitted to the ICU (10.8%). The mortality rate was 18%, which was lower than in the matched general population (SMR = 95.5 [95% CI 94.2-96.8]). Overall, 35 patients (31.5%) met criteria of severe COVID-19. Baseline immunosuppression containing mycophenolate was an independent predictor of severe COVID-19 (relative risk = 3.94; 95% CI 1.59-9.74; p = 0.003), particularly at doses higher than 1,000 mg/day (p = 0.003). This deleterious effect was not observed with calcineurin inhibitors or everolimus and complete immunosuppression withdrawal showed no benefit. Being chronically immunosuppressed, liver transplant patients have an increased risk of acquiring COVID-19 but their mortality rates are lower than the matched general population. Upon hospital admission, mycophenolate dose reduction or withdrawal could help in preventing severe COVID-19. However, complete immunosuppression withdrawal should be discouraged. In liver transplant patients, chronic immunosuppression increases the risk of acquiring COVID-19 but it could reduce disease severity. Complete immunosuppression withdrawal may not be justified. However, mycophenolate withdrawal or temporary conversion to calcineurin inhibitors or everolimus until disease resolution could be beneficial in hospitalised patients.

Sections du résumé

BACKGROUND & AIMS
The incidence and outcomes of coronavirus disease 2019 (COVID-19) in immunocompromised patients are a matter of debate.
METHODS
We performed a prospective nationwide study including a consecutive cohort of liver transplant patients with COVID-19 recruited during the Spanish outbreak from 28 February to 7 April, 2020. The primary outcome was severe COVID-19, defined as the need for mechanical ventilation, intensive care, and/or death. Age- and gender-standardised incidence and mortality ratios (SIR and SMR) were calculated using data from the Ministry of Health and the Spanish liver transplant registry. Independent predictors of severe COVID-19 among hospitalised patients were analysed using multivariate Cox regression.
RESULTS
A total of 111 liver transplant patients were diagnosed with COVID-19 (SIR = 191.2 [95% CI 190.3-192.2]). The epidemiological curve and geographic distribution overlapped widely between the liver transplant and general populations. After a median follow-up of 23 days, 96 patients (86.5%) were admitted to hospital and 22 patients (19.8%) required respiratory support. A total of 12 patients were admitted to the ICU (10.8%). The mortality rate was 18%, which was lower than in the matched general population (SMR = 95.5 [95% CI 94.2-96.8]). Overall, 35 patients (31.5%) met criteria of severe COVID-19. Baseline immunosuppression containing mycophenolate was an independent predictor of severe COVID-19 (relative risk = 3.94; 95% CI 1.59-9.74; p = 0.003), particularly at doses higher than 1,000 mg/day (p = 0.003). This deleterious effect was not observed with calcineurin inhibitors or everolimus and complete immunosuppression withdrawal showed no benefit.
CONCLUSIONS
Being chronically immunosuppressed, liver transplant patients have an increased risk of acquiring COVID-19 but their mortality rates are lower than the matched general population. Upon hospital admission, mycophenolate dose reduction or withdrawal could help in preventing severe COVID-19. However, complete immunosuppression withdrawal should be discouraged.
LAY SUMMARY
In liver transplant patients, chronic immunosuppression increases the risk of acquiring COVID-19 but it could reduce disease severity. Complete immunosuppression withdrawal may not be justified. However, mycophenolate withdrawal or temporary conversion to calcineurin inhibitors or everolimus until disease resolution could be beneficial in hospitalised patients.

Identifiants

pubmed: 32750442
pii: S0168-8278(20)30521-3
doi: 10.1016/j.jhep.2020.07.040
pmc: PMC7395653
pii:
doi:

Substances chimiques

Calcineurin Inhibitors 0
Immunosuppressive Agents 0
Mycophenolic Acid HU9DX48N0T

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

148-155

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Conflicts of interest JC has received lecture fees from Chiesi, Astellas, and Novartis and is an advisory to Chiesi. MR-P has received lecture fees from Astellas, Novartis, and Intercept Pharma. MS has received lecture fees from Astellas, Novartis, and Chiesi and is an advisory to Jazz and Novartis. MG has received speaker fees from and/or acted as advisor for Astellas, Novartis, Chiesi, Baxter, and Medtronic. MN has received lecture fees from Astellas Pharma. MI has received lecture fees from BMS. CV has received lecture fees from Novartis, Abbie, and Gilead. AC has received lecture fees from Astellas Pharma. GB-F has received lecture fees from Bayer and Astellas. JLM has received lecture fees from Bayer and Gilead. JP has received lecture fees by Astellas, Chiesi, and Gilead. AA-M, AM-S, JG, JN, JB-S, AC, LL, AC, AF-Y, CL, IF, CF, LC, SP, PR, MG-D, RG-G, LH, FN, AO, JA, EF, FG-P, ST and GDR have no conflict of interest to disclose regarding this manuscript. Please refer to the accompanying ICMJE disclosure forms for further details.

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Auteurs

Jordi Colmenero (J)

Liver Transplant Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.

Manuel Rodríguez-Perálvarez (M)

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; Department of Hepatology and Liver Transplantation, Hospital Universitario Reina Sofía, IMIBIC, Cordoba, Spain. Electronic address: ropeml@hotmail.com.

Magdalena Salcedo (M)

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; Hepatology and Liver Transplantation Unit, Hospital General Universitario Gregorio Marañón, Universidad Complutense, Madrid, Spain.

Ana Arias-Milla (A)

Hepatology and Liver Transplant Unit, Hospital Puerta de Hierro, IDIPHIMSA, Universidad Autónoma de Madrid, Madrid, Spain.

Alejandro Muñoz-Serrano (A)

Hepatology and Liver Transplant Unit, Hospital Puerta de Hierro, IDIPHIMSA, Universidad Autónoma de Madrid, Madrid, Spain.

Javier Graus (J)

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; Department of Digestive Diseases, Hospital Ramón y Cajal, IRYCIS, Madrid, Spain.

Javier Nuño (J)

Hepatobiliary and Liver Transplantation Unit, Hospital Universitario Ramón y Cajal, Madrid, Spain.

Mikel Gastaca (M)

Liver Transplantation Unit, Cruces University Hospital, University of the Basque Country, Biocruces Bizkaia Health Research Institute, Bilbao, Spain.

Javier Bustamante-Schneider (J)

Liver Transplantation Unit, Cruces University Hospital, University of the Basque Country, Biocruces Bizkaia Health Research Institute, Bilbao, Spain.

Alba Cachero (A)

Liver Transplant Unit, Hospital Universitari de Bellvitge, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.

Laura Lladó (L)

Liver Transplant Unit, Hospital Universitari de Bellvitge, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.

Aránzazu Caballero (A)

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; Hepatology and Liver Transplantation Unit, Hospital General Universitario Gregorio Marañón, Universidad Complutense, Madrid, Spain.

Ainhoa Fernández-Yunquera (A)

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; Hepatology and Liver Transplantation Unit, Hospital General Universitario Gregorio Marañón, Universidad Complutense, Madrid, Spain.

Carmelo Loinaz (C)

Department of Hepatology/HPB-surgery/Transplantation, Hospital Universitario 12 de Octubre, Madrid, Spain.

Inmaculada Fernández (I)

Department of Hepatology/HPB-surgery/Transplantation, Hospital Universitario 12 de Octubre, Madrid, Spain.

Constantino Fondevila (C)

Liver Transplant Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.

Miquel Navasa (M)

Liver Transplant Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.

Mercedes Iñarrairaegui (M)

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; Liver Unit, Clínica Universidad de Navarra, IDISNA, Pamplona, Spain.

Lluis Castells (L)

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; Department of Internal Medicine, Liver Unit, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

Sonia Pascual (S)

Liver Unit, Hospital General Universitario de Alicante, Alicante, Spain.

Pablo Ramírez (P)

Liver Transplantation Unit, Liver Unit, Department of Surgery, IMIB, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain.

Carmen Vinaixa (C)

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; Department of Hepatology and Liver Transplantation, Hospital Universitario y Politécnico La Fe, Valencia, Spain.

María Luisa González-Dieguez (ML)

Liver Unit and Division of Gastroenterology and Hepatology, Hospital Universitario Central de Asturias, Oviedo, Spain.

Rocío González-Grande (R)

Department of Liver Transplantation, Hospital Regional Universitario de Málaga, Malaga, Spain.

Loreto Hierro (L)

Department of Paediatric Hepatology and Liver Transplantation, Hospital Universitario La Paz, Madrid, Spain.

Flor Nogueras (F)

Department of Hepatology and Liver Transplantation, Hospital Virgen de las Nieves, Granada, Spain.

Alejandra Otero (A)

Liver Transplant Unit, Hospital de A Coruña, A Coruña, Spain.

José María Álamo (JM)

Liver Transplant Unit, Hospital Virgen del Rocío, Seville, Spain.

Gerardo Blanco-Fernández (G)

Department of HPB surgery and Liver Transplantation, Complejo Hospitalario Universitario de Badajoz, Badajoz, Spain.

Emilio Fábrega (E)

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; Department of Digestive Diseases, IDIVAL, Hospital Universitario Marqués de Valdecilla, Santander, Spain.

Fernando García-Pajares (F)

Department of Liver Transplantation, Hospital Río Hortega de Valladolid, Valladolid, Spain.

José Luis Montero (JL)

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; Department of Hepatology and Liver Transplantation, Hospital Universitario Reina Sofía, IMIBIC, Cordoba, Spain.

Santiago Tomé (S)

Department of Liver Transplantation, Hospital Universitario de Santiago, Santiago de Compostela, Spain.

Gloria De la Rosa (G)

Registro Español de Trasplante Hepático (RETH) y Organización Nacional de Trasplantes (ONT), Madrid, Spain.

José Antonio Pons (JA)

Liver Transplantation Unit, Liver Unit, Department of Surgery, IMIB, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain.

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