American Association for the Study of Liver Diseases Expert Panel Consensus Statement: Vaccines to Prevent Coronavirus Disease 2019 Infection in Patients With Liver Disease

Oren K Fix, Emily A Blumberg, Kyong-Mi Chang, Jaime Chu, Raymond T Chung, Elizabeth K Goacher, Bilal Hameed, Daniel R Kaul, Laura M Kulik, Ryan M Kwok, Brendan M McGuire, David C Mulligan, Jennifer C Price, Nancy S Reau, K Rajender Reddy, Andrew Reynolds, Hugo R Rosen, Mark W Russo, Michael L Schilsky, Elizabeth C Verna, John W Ward, Robert J Fontana, AASLD COVID‐19 Vaccine Working Group, Oren K Fix, Emily A Blumberg, Kyong-Mi Chang, Jaime Chu, Raymond T Chung, Elizabeth K Goacher, Bilal Hameed, Daniel R Kaul, Laura M Kulik, Ryan M Kwok, Brendan M McGuire, David C Mulligan, Jennifer C Price, Nancy S Reau, K Rajender Reddy, Andrew Reynolds, Hugo R Rosen, Mark W Russo, Michael L Schilsky, Elizabeth C Verna, John W Ward, Robert J Fontana, AASLD COVID‐19 Vaccine Working Group

Abstract

The aim of this document is to provide a concise scientific review of the currently available COVID-19 vaccines and those in development, including mRNA, adenoviral vectors, and recombinant protein approaches. The anticipated use of COVID-19 vaccines in patients with chronic liver disease (CLD) and liver transplant (LT) recipients is reviewed and practical guidance is provided for health care providers involved in the care of patients with liver disease and LT about vaccine prioritization and administration. The Pfizer and Moderna mRNA COVID-19 vaccines are associated with a 94%-95% vaccine efficacy compared to placebo against COVID-19. Local site reactions of pain and tenderness were reported in 70%-90% of clinical trial participants, and systemic reactions of fever and fatigue were reported in 40%-70% of participants, but these reactions were generally mild and self-limited and occurred more frequently in younger persons. Severe hypersensitivity reactions related to the mRNA COVID-19 vaccines are rare and more commonly observed in women and persons with a history of previous drug reactions for unclear reasons. Because patients with advanced liver disease and immunosuppressed patients were excluded from the vaccine licensing trials, additional data regarding the safety and efficacy of COVID-19 vaccines are eagerly awaited in these and other subgroups. Remarkably safe and highly effective mRNA COVID-19 vaccines are now available for widespread use and should be given to all adult patients with CLD and LT recipients. The online companion document located at https://www.aasld.org/about-aasld/covid-19-resources will be updated as additional data become available regarding the safety and efficacy of other COVID-19 vaccines in development.

© 2021 by the American Association for the Study of Liver Diseases.

Figures

FIG. 1
FIG. 1
COVID‐19 vaccine delivery systems. (A) mRNA vaccines.

  1. The mRNA is surrounded by a lipid nanoparticle.

  2. The lipid nanoparticle assists with cell entry.

  3. mRNA is released into the cytoplasm.

  4. Ribosomes and cellular proteins are used to translate the mRNA into the spike protein.

  5. The spike protein gets expressed on the cell surface and/or secreted into the serum.

  6. The spike proteins expressed on the cell surface by the MHC receptors can activate T cells, which can activate the immune system, for additional T cells, B cells, and the production of antibodies against the spike protein.

  7. Antigen‐presenting cells can engulf secreted spike proteins, which can also activate the immune system.

(B) Adenoviral vector vaccines.

  1. The adenovirus contains DNA, which includes genetic material to produce the spike protein.

  2. The adenovirus is taken up by the human cell.

    1. The adenovirus enters the cytoplasm.

    2. The adenovirus releases its DNA into the nucleus.

    3. Transcription of the DNA to mRNA occurs in the nucleus.

    4. mRNA is transferred into the cytoplasm.

  3. Ribosomes and cellular proteins are used to translate the mRNA into the spike protein.

  4. The spike protein gets expressed on the cell surface and/or secreted into the serum.

  5. The spike proteins expressed on the cell surface by the MHC receptors can activate T cells, which can activate the immune system, for additional T cells, B cells, and the production of antibodies against the spike protein.

  6. Antigen‐presenting cells can engulf secreted spiked proteins, which can also activate the immune system.

(C) Weakened live attenuated virus vaccines.

  1. Weakened live attenuated virus containing the mRNA of the spike protein

  2. The attenuated virus binds to the ACE2 for cell entry.

  3. mRNA is released into the cytoplasm.

  4. Ribosomes and cellular proteins are used to translate the mRNA into the spiked protein.

  5. The spike protein gets expressed on the cell surface and/or secreted into the serum.

  6. The spike proteins expressed on the cell surface by the MHC receptors can activate T cells, which can activate the immune system, for additional T cells, B cells, and the production of antibodies against the spike protein.

  7. Antigen‐presenting cells can engulf secreted spiked proteins, which can also activate the immune system.

FIG. 2
FIG. 2
Cumulative incidence of first COVID‐19 occurrence in phase 3 clinical trials. Vaccine and placebo groups diverge at approximately 14 days after the first dose (arrow). (A) Pfizer‐BioNTech (BNT162b2). (B) Moderna (mRNA‐1273).
FIG. 3
FIG. 3
Frequency of adverse events of FDA EUA mRNA vaccines compared to placebo. (A) Pfizer‐BioNTech (BNT162b2). (B) Moderna (mRNA‐1273).

References

    1. Bonnel AR, Bunchorntavakul C, Reddy KR. Immune dysfunction and infections in patients with cirrhosis. Clin Gastroenterol Hepatol 2011;9:727‐738.
    1. Van Kerkhove MD, Vandemaele KAH, Shinde V, Jaramillo‐Gutierrez G, Koukounari A, Donnelly CA, et al. Risk factors for severe outcomes following 2009 influenza A (H1N1) infection: a global pooled analysis. PLoS Med 2011;8:e1001053.
    1. van Hoek AJ, Andrews N, Waight PA, Stowe J, Gates P, George R, et al. The effect of underlying clinical conditions on the risk of developing invasive pneumococcal disease in England. J Infect 2012;65:17‐24.
    1. Gutierrez Domingo I, Pascasio Acevedo JM, Alcalde Vargas A, Ramos Cuadra A, Ferrer Ríos MT, Sousa Martin JM, et al. Response to vaccination against hepatitis B virus with a schedule of four 40‐μg doses in cirrhotic patients evaluated for liver transplantation: factors associated with a response. Transplant Proc 2012;44:1499‐1501.
    1. Bonazzi PR, Bacchella T, Freitas AC, Osaki KT, Lopes MH, Freire MP, et al. Double‐dose hepatitis B vaccination in cirrhotic patients on a liver transplant waiting list. Braz J Infect Dis 2008;12:306‐309.
    1. CDC . ACIP general best practice guidelines for immunization. Published November 20, 2020. . Accessed February 2021.
    1. Belouzard S, Millet JK, Licitra BN, Whittaker GR. Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses 2012;4:1011‐1033.
    1. Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, et al. A new coronavirus associated with human respiratory disease in China. Nature 2020;579:265‐269.
    1. U.S. Department of Defense . Coronavirus: Operation Warp Speed timeline. Page updated January 22, 2021. . Accessed February 2021.
    1. Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, et al. An mRNA vaccine against SARS‐CoV‐2—preliminary report. N Engl J Med 2020;12:1920‐1931.
    1. Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and efficacy of the BNT162b2 mRNA Covid‐19 vaccine. N Engl J Med 2020;31:2603‐2615.
    1. Pardi N, Hogan MJ, Naradikian MS, Parkhouse K, Cain DW, Jones L, et al. Nucleoside‐modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. J Exp Med 2018;4:1571‐1588.
    1. Reichmuth AM, Oberli MA, Jaklenec A, Langer R, Blankschtein D. mRNA vaccine delivery using lipid nanoparticles. Ther Deliv 2016;7:319‐334.
    1. Buschmann MD, Carrasco MJ, Alishetty S, Paige M, Alameh MG, Weissman D. Nanomaterial delivery systems for mRNA vaccines. Vaccines (Basel) 2021;19:65.
    1. Kelly C, Swadling L, Capone S, Brown A, Richardson R, Halliday J, et al. Chronic hepatitis C viral infection subverts vaccine‐induced T‐cell immunity in humans. Hepatology 2016;63:1455‐1470.
    1. Swadling L, Halliday J, Kelly C, Brown A, Capone S, Ansari MA, et al. Highly‐immunogenic virally‐vectored T‐cell vaccines cannot overcome subversion of the T‐cell response by HCV during chronic infection. Vaccines (Basel) 2016;2:27.
    1. Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, et al. Safety and efficacy of the ChAdOx1 nCoV‐19 vaccine (AZD1222) against SARS‐CoV‐2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2021;9:99‐111.
    1. AstraZeneca . AstraZeneca’s COVID‐19 vaccine authorised for emergency supply in the UK. Published December 30, 2020. . Accessed February 2021.
    1. Johnson & Johnson Press Release . Johnson & Johnson announces single‐shot Janssen COVID‐19 vaccine candidate met primary endpoints in interim analysis of its phase 3 ENSEMBLE trial. Published January 29, 2021. . Accessed February 2021.
    1. Zhu FC, Li YH, Guan XH, Hou LH, Wang WJ, Li JX, et al. Safety, tolerability, and immunogenicity of a recombinant adenovirus type‐5 vectored COVID‐19 vaccine: a dose‐escalation, open‐label, non‐randomised, first‐in‐human trial. Lancet 2020;13:1845‐1854.
    1. Cao Y, Zhu X, Hossen MN, Kakar P, Zhao Y, Chen X. Augmentation of vaccine‐induced humoral and cellular immunity by a physical radiofrequency adjuvant. Nat Commun 2018;12:3695.
    1. Novavax Press Release . Novavax COVID‐19 vaccine demonstrates 89.3% efficacy in UK phase 3 trial. Published January 28, 2021. . Accessed February 2021.
    1. COVID‐19 Real‐Time Learning Network . Vaccines & Immunity. 2020. . Accessed February 2021.
    1. Janssen Press Release . Johnson & Johnson announces submission of application to the U.S. FDA for Emergency Use Authorization of its investigational single‐shot Janssen COVID‐19 vaccine candidate. Published February 4, 2021. . Accessed February 2021.
    1. U.S. Department of Health & Human Services, CDC Morbidity and Mortality Weekly Report (MMWR) . Allergic reactions including anaphylaxis after receipt of the first dose of Pfizer‐BioNTech COVID‐19 vaccine—United States, December 14‐23, 2020. MMWR Morb Mortal Wkly Rep 2021;70:46‐ 51.
    1. U.S. Department of Health & Human Services, CDC Morbidity and Mortality Weekly Report (MMWR) . Allergic reactions including anaphylaxis after receipt of the first dose of Moderna COVID‐19 vaccine—United States, December 21, 2020–January 10, 2021. MMWR Morb Mortal Wkly Rep 2021;70:125‐129.
    1. Castells MC, Phillips EJ. Maintaining safety with SARS‐CoV‐2 vaccines. N Engl J Med 2021;384:643‐649.
    1. Volz E, Mishra S, Chand M, Barrett JC, Johnson R, Geidelberg L, et al. Transmission of SARS‐CoV‐2 lineage B.1.1.7 in England: insights from linking epidemiological and genetic data. MedRxiv 2021. Jan 4. 10.1101/2020.12.30.20249034. [Preprint article that has not been peer‐reviewed]
    1. Tegally H, Wilkinson E, Giovanetti M, Iranzadeh A, Fonseca V, Giandhari J, et al. Emergence and rapid spread of a new severe acute respiratory syndrome‐related coronavirus 2 (SARS‐CoV‐2) lineage with multiple spike mutations in South Africa. MedRxiv 2020. Dec 22. 10.1101/2020.12.21.20248640. [Preprint article that has not been peer‐reviewed]
    1. Faria NR, Claro IM, Candido D, Moyses Franco LA, Andrade PS, Coletti TM, et al. Genomic characterisation of an emergent SARS‐CoV‐2 lineage in Manaus: preliminary findings—SARS‐CoV‐2 coronavirus / nCoV‐2019 Genomic Epidemiology. Virological. Published January 12, 2021. . Accessed February 2021.
    1. Galloway SE, Paul P, MacCannell DR, Johansson MA, Brooks JT, MacNeil A, et al. Emergence of SARS‐CoV‐2 B.1.1.7 lineage—United States, December 29, 2020‐January 12, 2021. MMWR Morb Mortal Wkly Rep 2021;70:95‐ 99.
    1. Gallagher J. Coronavirus: UK variant ‘may be more deadly.’ BBC News. Published January 22, 2021. . Accessed February 2021.
    1. Xie X, Zou J, Fontes‐Garfias CR, Xia H, Swanson KA, Cutler M, et al. Neutralization of N501Y mutant SARS‐CoV‐2 by BNT162b2 vaccine‐elicited sera. BioRxiv 2021. Jan 7. 10.1101/2021.01.07.425740. [Preprint article that has not been peer‐reviewed]
    1. Muik A, Wallisch AK, Sänger B, Swanson KA, Mühl J, Chen W, et al. Neutralization of SARS‐CoV‐2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine‐elicited human sera. BioRxiv 2021. Jan 19. 10.1101/2021.01.18.426984. [Preprint article that has not been peer‐reviewed]
    1. Wu K, Werner AP, Moliva JI, Koch M, Choi A, Stewart‐Jones GBE, et al. mRNA‐1273 vaccine induces neutralizing antibodies against spike mutants from global SARS‐CoV‐2 variants. BioRxiv 2021. Jan 25. 10.1101/2021.01.25.427948. [Preprint article that has not been peer‐reviewed]
    1. Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams MM, Son MBF, et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med 2020;23:334‐346.
    1. Lobritto S, Danziger‐Isakov L, Michaels MG, Mazariegos GV. Impact of COVID‐19 pandemic on pediatrics and pediatric transplantation programs. Front Pediatr 2020;8:612627.
    1. CDC . COVID‐19 vaccination provider requirements and support. Published January 7, 2021. . Accessed February 2021.
    1. CDC . COVID‐19: when vaccine is limited, who gets vaccinated first. Published December 31, 2020. . Accessed February 2021.
    1. CDC . The importance of COVID‐19 vaccination for healthcare personnel. Published February 11, 2020. . Accessed February 2021.
    1. Iavarone M, D’Ambrosio R, Soria A, Triolo M, Pugliese N, Del Poggio P, et al. High rates of 30‐day mortality in patients with cirrhosis and COVID‐19. J Hepatol 2020;73:1063‐1071.
    1. Williamson EJ, Walker AJ, Bhaskaran K, Bacon S, Bates C, Morton CE, et al. Factors associated with COVID‐19‐related death using OpenSAFELY. Nature 2020;584:430‐436.
    1. Moon AM, Webb GJ, Aloman C, Armstrong MJ, Cargill T, Dhanasekaran R, et al. High mortality rates for SARS‐CoV‐2 infection in patients with pre‐existing chronic liver disease and cirrhosis: preliminary results from an international registry. J Hepatol 2020;73:705‐708.
    1. Singh S, Khan A. Clinical characteristics and outcomes of COVID‐19 among patients with pre‐existing liver disease in United States: a multi‐center research network study. Gastroenterology 2020;159:768‐771.
    1. Bajaj JS, Garcia‐Tsao G, Biggins SW, Kamath PS, Wong F, McGeorge S, et al. Comparison of mortality risk in patients with cirrhosis and COVID‐19 compared with patients with cirrhosis alone and COVID‐19 alone: multicentre matched cohort. Gut 2021;70:531‐536.
    1. Krammer F, Srivastava K, the PARIS Team , Simon V. Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS‐CoV‐2 mRNA vaccine. MedRxiv 2021. Feb 1. 10.1101/2021.01.29.21250653. [Preprint article that has not been peer‐reviewed]
    1. CDC . COVID‐19: people with certain medical conditions. Published December 29, 2020. . Accessed February 2021.
    1. Gerussi A, Rigamonti C, Elia C, Cazzagon N, Floreani A, Pozzi R, et al. Coronavirus Disease 2019 (COVID‐19) in autoimmune hepatitis: a lesson from immunosuppressed patients. Hepatol Commun 2020;9:1257‐1262.
    1. Colmenero J, Rodríguez‐Perálvarez M, Salcedo M, Arias‐Milla A, Muñoz‐Serrano A, Graus J, et al. Epidemiological pattern, incidence and outcomes of COVID‐19 in liver transplant patients. J Hepatol 2021;74:148‐155.
    1. Webb GJ, Marjot T, Cook JA, Aloman C, Armstrong MJ, Brenner EJ, et al. Outcomes following SARS‐CoV‐2 infection in liver transplant recipients: an international registry study. Lancet Gastroenterol Hepatol 2020;5:1008‐1016.
    1. Marjot T, Webb GJ, Barritt AS, Ginès P, Lohse AW, Moon AM, et al. SARS‐CoV‐2 vaccination in patients with liver disease: responding to the next big question. Lancet Gastroenterol Hepatol 2021. Jan 11. 10.1016/S2468-1253(21)00008-X. [Online ahead of print]
    1. Forde KA, Tanapanpanit O, Reddy KR. Hepatitis B and C in African Americans: current status and continued challenges. Clin Gastroenterol Hepatol 2014;12:738‐748.
    1. Sheka AC, Adeyi O, Thompson J, Hameed B, Crawford PA, Ikramuddin S. Nonalcoholic steatohepatitis: a review. JAMA 2020;24:1175‐1183.
    1. Mendenhall C, Roselle GA, Lybecker LA, Marshall LE, Grossman CJ, Myre SA, et al. Hepatitis B vaccination. Response of alcoholic with and without liver injury. Dig Dis Sci 1988;33:263‐269.
    1. Dumot JA, Barnes DS, Younossi Z, Gordon SM, Avery RK, Domen RE, et al. Immunogenicity of hepatitis A vaccine in decompensated liver disease. Am J Gastroenterol 1999;94:1601‐1604.
    1. Carey W, Pimentel R, Westveer MK, Vogt D, Broughan T. Failure of hepatitis B immunization in liver transplant recipients: results of a prospective trial. Am J Gastroenterol 1990;85:1590‐1592.
    1. Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and safety of the mRNA‐1273 SARS‐CoV‐2 vaccine. N Engl J Med 2021;4:403‐416.
    1. Sadoff J, Le Gars M, Shukarev G, Heerwegh D, Truyers C, de Groot AM, et al. Interim results of a phase 1‐2a trial of Ad26.COV2.S Covid‐19 vaccine. N Engl J Med 2021. Jan 13. 10.1056/NEJMoa2034201. [Online ahead of print]
    1. Zhu FC, Guan XH, Li YH, Huang JY, Jiang T, Hou LH, et al. Immunogenicity and safety of a recombinant adenovirus type‐5‐vectored COVID‐19 vaccine in healthy adults aged 18 years or older: a randomised, double‐blind, placebo‐controlled, phase 2 trial. Lancet 2020;15:479‐488.
    1. Simões E. New Brazil data shows disappointing 50.4% efficacy for China’s CoronaVac vaccine. Reuters. Published January 13, 2021. . Accessed February 2021.
    1. Xia S, Zhang Y, Wang Y, Wang H, Yang Y, Gao GF, et al. Safety and immunogenicity of an inactivated SARS‐CoV‐2 vaccine, BBIBP‐CorV: a randomised, double‐blind, placebo‐controlled, phase 1/2 trial. Lancet Infect Dis 2021;21:39‐51.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する