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

被引：12

作者：

Murray, Sam M. ^{[1
]}

Pose, Elisa ^{[2
,3
]}

Wittner, Melanie ^{[4
,5
]}

Londono, Maria-Carlota ^{[2
,3
]}

Schaub, Golda ^{[4
,5
]}

Cook, Jonathan ^{[6
]}

Dimitriadis, Stavros ^{[7
]}

Meacham, Georgina ^{[7
]}

Irwin, Sophie ^{[7
]}

Lim, Zixiang ^{[7
]}

Duengelhoef, Paul ^{[5
]}

Sterneck, Martina ^{[5
]}

Lohse, Ansgar W. ^{[4
,5
]}

Perez, Valeria ^{[2
,3
,8
]}

Trivedi, Palak ^{[9
,10
]}

Bhandal, Khush ^{[10
]}

Mullish, Benjamin H. ^{[11
,12
]}

Manousou, Pinelopi ^{[11
,12
]}

Provine, Nicholas M. ^{[7
]}

Avitabile, Emma ^{[2
,3
]}

Carroll, Miles ^{[13
]}

Tipton, Tom ^{[13
]}

Healy, Saoirse ^{[13
]}

Burra, Patrizia ^{[14
]}

Klenerman, Paul ^{[1
,7
,15
]}

Dunachie, Susanna ^{[1
,15
,16
]}

Kronsteiner, Barbara ^{[1
,15
,16
]}

Maciola, Agnieszka Katarzyna ^{[17
]}

Pasqual, Giulia ^{[17
,18
]}

Hernandez-Gea, Virginia ^{[2
,3
,8
]}

Garcia-Pagan, Juan Carlos ^{[2
,3
,8
]}

Lampertico, Pietro ^{[19
,20
]}

Iavarone, Massimo ^{[19
]}

Gines, Pere ^{[2
,3
]}

Luetgehetmann, Marc ^{[5
,21
]}

zur Wiesch, Julian Schulze ^{[4
,5
]}

Russo, Francesco Paolo ^{[14
]}

Barnes, Eleanor ^{[1
,15
]}

Marjot, Thomas ^{[22
,23
]}

机构：

[1] Univ Oxford, Nuffield Dept Clin Med, Peter Medawar Bldg Pathogen Res, Oxford, England

[2] Univ Barcelona, Hosp Clin, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Liver Unit, Barcelona, Spain

[3] CIBERehd Ctr Invest Biomed Red Enfermedades Hepat, Madrid, Spain

[4] German Ctr Infect Res DZIF, Partner Site Hamburg Lubeck Borstel Riems, Borstel, Germany

[5] Univ Med Ctr Hamburg Eppendorf, Dept Internal Med, Hamburg, Germany

[6] Univ Oxford, Ctr Stat Med, Oxford, England

[7] Univ Oxford, Nuffield Dept Med, Translat Gastroenterol Unit, Oxford, England

[8] European Reference Network Rare Liver Disorders E, Barcelona, Germany

[9] Univ Birmingham, Natl Inst Hlth Res Birmingham, Inst Immunol & Immunotherapy, Ctr Liver & Gastrointestinal Res,Biomed Res Ctr, Birmingham, W Midlands, England

[10] Univ Hosp Birmingham NHS Fdn Trust, Queen Elizabeth Hosp, Liver Unit, Birmingham, W Midlands, England

[11] Imperial Coll London, Fac Med, Dept Metab Digest & Reprod, Div Digest Dis, London, England

[12] Imperial Coll Healthcare NHS Trust, St Marys Hosp, Dept Hepatol, London, England

[13] Univ Oxford, Wellcome Ctr Human Genet, Oxford, England

[14] Univ Padua, Dept Surg Oncol & Gastroenterol DISCOG, Padua, Italy

[15] Oxford Univ Hosp NHS Trust, Oxford NIHR Biomed Res Ctr, Oxford, England

[16] Univ Mahidol, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand

[17] Univ Padua, Dept Surg Oncol & Gastroenterol, Lab Synthet Immunol, Padua, Italy

[18] Veneto Inst Oncol IOV IRCCS, Padua, Italy

[19] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Div Gastroenterol & Hepatol, Milan, Italy

[20] Univ Milan, CRC AM & A Migliavacca Ctr Liver Dis, Dept Pathophysiol & Transplantat, Milan, Italy

[21] Univ Med Ctr Hamburg Eppendorf, Inst Med Microbiol Virol & Hyg, Hamburg, Germany

[22] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab OCDEM, NIHR Oxford Biomed Res Ctr, Oxford, England

[23] Oxford Univ Hosp NHS Fdn Trust, John Radcliffe Hosp, Oxford Liver Unit, Oxford OX3 9DU, England

来源：

JOURNAL OF HEPATOLOGY | 2024年 / 80卷 / 01期

关键词：

COVID-19; Vaccination; Liver transplantation; Autoimmune hepatitis; Cirrhosis; Vascular liver disease; T cells; Antibodies; SARS-CoV-2; Variants of Concern; MESSENGER-RNA; IMMUNOGENICITY; IMPACT;

D O I：

10.1016/j.jhep.2023.10.009

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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 IFN gamma 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. (c) 2023 The Author(s). Published by Elsevier B. V. on behalf of European Association for the Study of the Liver. This is an open access article under the CC By license (https://creativecommons.org/licenses/by/4.0/)

引用

页码：109 / 123

页数：16

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