Immune responses and clinical outcomes after COVID-19 vaccination in patients with liver disease and liver transplant recipients

Issued Date

2023-01-01

Resource Type

Article

ISSN

01688278

eISSN

16000641

DOI

10.1016/j.jhep.2023.10.009

Scopus ID

2-s2.0-85178338334

Journal Title

Journal of Hepatology

Rights Holder(s)

SCOPUS

Bibliographic Citation

Journal of Hepatology (2023)

Suggested Citation

Murray S.M., Pose E., Wittner M., Londoño M.C., Schaub G., Cook J., Dimitriadis S., Meacham G., Irwin S., Lim Z., Duengelhoef P., Sterneck M., Lohse A.W., Perez V., Trivedi P., Bhandal K., Mullish B.H., Manousou P., Provine N.M., Avitabile E., Carroll M., Tipton T., Healy S., Burra P., Klenerman P., Dunachie S., Kronsteiner B., Maciola A.K., Pasqual G., Hernandez-Gea V., Garcia-Pagan J.C., Lampertico P., Iavarone M., Gines P., Lütgehetmann M., Schulze zur Wiesch J., Russo F.P., Barnes E., Marjot T. Immune responses and clinical outcomes after COVID-19 vaccination in patients with liver disease and liver transplant recipients. Journal of Hepatology (2023). doi:10.1016/j.jhep.2023.10.009 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/91423

Title

Immune responses and clinical outcomes after COVID-19 vaccination in patients with liver disease and liver transplant recipients

Author(s)

Murray S.M.
 Pose E.
 Wittner M.
 Londoño M.C.
 Schaub G.
 Cook J.
 Dimitriadis S.
 Meacham G.
 Irwin S.
 Lim Z.
 Duengelhoef P.
 Sterneck M.
 Lohse A.W.
 Perez V.
 Trivedi P.
 Bhandal K.
 Mullish B.H.
 Manousou P.
 Provine N.M.
 Avitabile E.
 Carroll M.
 Tipton T.
 Healy S.
 Burra P.
 Klenerman P.
 Dunachie S.
 Kronsteiner B.
 Maciola A.K.
 Pasqual G.
 Hernandez-Gea V.
 Garcia-Pagan J.C.
 Lampertico P.
 Iavarone M.
 Gines P.
 Lütgehetmann M.
 Schulze zur Wiesch J.
 Russo F.P.
 Barnes E.
 Marjot T.

Author's Affiliation

Mahidol Oxford Tropical Medicine Research Unit
 NIHR Oxford Biomedical Research Centre
 NIHR Birmingham Biomedical Research Centre
 Istituto Oncologico Veneto IOV - IRCCS
 The Wellcome Centre for Human Genetics
 Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
 Università degli Studi di Milano
 St Mary's Hospital
 Imperial College Faculty of Medicine
 Queen Elizabeth Hospital Birmingham
 Nuffield Department of Medicine
 John Radcliffe Hospital
 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
 Universitätsklinikum Hamburg-Eppendorf
 University of Oxford Medical Sciences Division
 Universitat de Barcelona
 Università degli Studi di Padova
 Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver)
 Partner Site Hamburg-Lübeck-Borstel-Riems

Other Contributor(s)

Mahidol University

Abstract

Background & Aims: Comparative assessments of immunogenicity following different COVID-19 vaccines in patients with distinct liver diseases are lacking. SARS-CoV-2-specific T-cell and antibody responses were evaluated longitudinally after one to three vaccine doses, with long-term follow-up for COVID-19-related clinical outcomes. Methods: A total of 849 participants (355 with cirrhosis, 74 with autoimmune hepatitis [AIH], 36 with vascular liver disease [VLD], 257 liver transplant recipients [LTRs] and 127 healthy controls [HCs]) were recruited from four countries. Standardised immune assays were performed pre and post three vaccine doses (V1-3). Results: In the total cohort, there were incremental increases in antibody titres after each vaccine dose (p <0.0001). Factors associated with reduced antibody responses were age and LT, whereas heterologous vaccination, prior COVID-19 and mRNA platforms were associated with greater responses. Although antibody titres decreased between post-V2 and pre-V3 (p = 0.012), patients with AIH, VLD, and cirrhosis had equivalent antibody responses to HCs post-V3. LTRs had lower and more heterogenous antibody titres than other groups, including post-V3 where 9% had no detectable antibodies; this was heavily influenced by intensity of immunosuppression. Vaccination increased T-cell IFNγ responses in all groups except LTRs. Patients with liver disease had lower functional antibody responses against nine Omicron subvariants and reduced T-cell responses to Omicron BA.1-specific peptides compared to wild-type. 122 cases of breakthrough COVID-19 were reported of which 5/122 (4%) were severe. Of the severe cases, 4/5 (80%) occurred in LTRs and 2/5 (40%) had no serological response post-V2. Conclusion: After three COVID-19 vaccines, patients with liver disease generally develop robust antibody and T-cell responses to vaccination and have mild COVID-19. However, LTRs have sustained no/low antibody titres and appear most vulnerable to severe disease. Impact and implications: Standardised assessments of the immune response to different COVID-19 vaccines in patients with liver disease are lacking. We performed antibody and T-cell assays at multiple timepoints following up to three vaccine doses in a large cohort of patients with a range of liver conditions. Overall, the three most widely available vaccine platforms were immunogenic and appeared to protect against severe breakthrough COVID-19. This will provide reassurance to patients with chronic liver disease who were deemed at high risk of severe COVID-19 during the pre-vaccination era, however, liver transplant recipients had the lowest antibody titres and remained vulnerable to severe breakthrough infection. We also characterise the immune response to multiple SARS-CoV-2 variants and describe the interaction between disease type, severity, and vaccine platform. These insights may prove useful in the event of future viral infections which also require rapid vaccine development and delivery to patients with liver disease.

Keyword(s)

Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/91423

Collections

Scopus 2023