Liver injury after SARS-CoV-2 vaccination: Features of immune-mediated hepatitis, role of corticosteroid therapy and outcome

Cumali Efe; Anand V. Kulkarni; Benedetta Terziroli Beretta-Piccoli; Bianca Magro; Albert Stättermayer; Mustafa Cengiz; Daniel Clayton-Chubb; Craig Lammert; Christine Bernsmeier; Özlem Gül; Fatima Higuera de la Tijera; Margarita Anders; Ellina Lytvyak; Mete Akın; Tugrul Purnak; Rodrigo Liberal; Mirta Peralta; Berat Ebik; Serkan Duman; Nurhan Demir; Yasemin Balaban; Álvaro Urzua; Fernando Contreras; Maria Grazia Venturelli; Yılmaz Bilgiç; Adriana Medina; Marcos Girala; Fulya Günşar; Maria Carlota Londoño; Theodoros Androutsakos; Ayelen Kisch; Alper Yurci; Fatih Güzelbulut; Yasir Furkan Çağın; Enver Avcı; Murat Akyıldız; Emine Kübra Dindar-Demiray; Murat Harputluoğlu; Rahul Kumar; Sanjaya K. Satapathy; Manuel Mendizabal; Marcelo Silva; Stefano Fagiuoli; Stuart K. Roberts; Neşe Karadağ Soylu; Ramazan Idilman; Eric M. Yoshida; Aldo J. Montano-Loza; George N. Dalekos; Ezequiel Ridruejo; Thomas D. Schiano; Staffan Wahlin

doi:10.1002/hep.32572

Liver injury after SARS-CoV-2 vaccination: Features of immune-mediated hepatitis, role of corticosteroid therapy and outcome

Cumali Efe
, Anand V. Kulkarni
, Benedetta Terziroli Beretta-Piccoli
, Bianca Magro
, Albert Stättermayer
, Mustafa Cengiz
, Daniel Clayton-Chubb
, Craig Lammert
, Christine Bernsmeier
, Özlem Gül
, Fatima Higuera de la Tijera
, Margarita Anders
, Ellina Lytvyak
, Mete Akın
, Tugrul Purnak
, Rodrigo Liberal
, Mirta Peralta
, Berat Ebik
, Serkan Duman
, Nurhan Demir

Yasemin Balaban, Álvaro Urzua, Fernando Contreras, Maria Grazia Venturelli, Yılmaz Bilgiç, Adriana Medina, Marcos Girala, Fulya Günşar, Maria Carlota Londoño, Theodoros Androutsakos, Ayelen Kisch, Alper Yurci, Fatih Güzelbulut, Yasir Furkan Çağın, Enver Avcı, Murat Akyıldız, Emine Kübra Dindar-Demiray, Murat Harputluoğlu, Rahul Kumar, Sanjaya K. Satapathy, Manuel Mendizabal, Marcelo Silva, Stefano Fagiuoli, Stuart K. Roberts, Neşe Karadağ Soylu, Ramazan Idilman, Eric M. Yoshida, Aldo J. Montano-Loza, George N. Dalekos, Ezequiel Ridruejo, Thomas D. Schiano, Staffan Wahlin

Division of Internal Medicine (Medicine)

Harran University
Asian Institute of Gastroenterology India
Università della Svizzera italiana
Epatocentro Ticino
Papa Giovanni XXIII Hospital
Medical University of Vienna
Gülhane Military Medical Academy
Alfred Health
Indiana University Bloomington
University of Basel
University Centre for Gastrointestinal and Liver Diseases
Kirikkale University
Hospital General de México
Hospital Alemán
University of Alberta
Akdeniz University
University of Texas Health Science Center at Houston
Centro Hospitalar Universitário de São João
World Gastroenterology Organization (WGO) Porto Training Center
Hospital de Infecciosas Francisco Javier Muñiz
Latin American Liver Research Educational and Awareness Network (LALREAN)
Gazi Yaşargil Education and Research Hospital
Ankara University
Ministry of Health, Turkey
Universidad de Chile
Centro de Gastroenterología Avanzada
Clinica Stella Maris
Inonu University
Universidad Nacional de Asunción
Ege University
August Pi i Sunyer Biomedical Research Institute
National and Kapodistrian University of Athens
Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo
Erciyes University
KTO Karatay University
Koc University
Bitlis Tatvan State Hospital
Changi General Hospital
Northwell Health System
Universidad Austral
Monash University
University of British Columbia
University Hospital of Larissa
Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno
Icahn School of Medicine at Mount Sinai
Karolinska Institutet

Research output: Contribution to journal › Article › peer-review

98 Citations (Scopus)

Abstract

Background and Aims: A few case reports of autoimmune hepatitis–like liver injury have been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We evaluated clinical features, treatment response and outcomes of liver injury following SARS-CoV-2 vaccination in a large case series. Approach and Results: We collected data from cases in 18 countries. The type of liver injury was assessed with the R-value. The study population was categorized according to features of immune-mediated hepatitis (positive autoantibodies and elevated immunoglobulin G levels) and corticosteroid therapy for the liver injury. We identified 87 patients (63%, female), median age 48 (range: 18–79) years at presentation. Liver injury was diagnosed a median 15 (range: 3–65) days after vaccination. Fifty-one cases (59%) were attributed to the Pfizer-BioNTech (BNT162b2) vaccine, 20 (23%) cases to the Oxford-AstraZeneca (ChAdOX1 nCoV-19) vaccine and 16 (18%) cases to the Moderna (mRNA-1273) vaccine. The liver injury was predominantly hepatocellular (84%) and 57% of patients showed features of immune-mediated hepatitis. Corticosteroids were given to 46 (53%) patients, more often for grade 3–4 liver injury than for grade 1–2 liver injury (88.9% vs. 43.5%, p = 0.001) and more often for patients with than without immune-mediated hepatitis (71.1% vs. 38.2%, p = 0.003). All patients showed resolution of liver injury except for one man (1.1%) who developed liver failure and underwent liver transplantation. Steroid therapy was withdrawn during the observation period in 12 (26%) patients after complete biochemical resolution. None had a relapse during follow-up. Conclusions: SARS-CoV-2 vaccination can be associated with liver injury. Corticosteroid therapy may be beneficial in those with immune-mediated features or severe hepatitis. Outcome was generally favorable, but vaccine-associated liver injury led to fulminant liver failure in one patient.

Original language	English
Pages (from-to)	1576-1586
Number of pages	11
Journal	Hepatology
Volume	76
Issue number	6
DOIs	https://doi.org/10.1002/hep.32572
Publication status	Published - Dec 2022

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SDG 3 Good Health and Well-being

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10.1002/hep.32572

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Efe, C., Kulkarni, A. V., Terziroli Beretta-Piccoli, B., Magro, B., Stättermayer, A., Cengiz, M., Clayton-Chubb, D., Lammert, C., Bernsmeier, C., Gül, Ö., la Tijera, F. H. D., Anders, M., Lytvyak, E., Akın, M., Purnak, T., Liberal, R., Peralta, M., Ebik, B., Duman, S., ... Wahlin, S. (2022). Liver injury after SARS-CoV-2 vaccination: Features of immune-mediated hepatitis, role of corticosteroid therapy and outcome. Hepatology, 76(6), 1576-1586. https://doi.org/10.1002/hep.32572

@article{db2268b091664114a101d2311dea038a,

title = "Liver injury after SARS-CoV-2 vaccination: Features of immune-mediated hepatitis, role of corticosteroid therapy and outcome",

abstract = "Background and Aims: A few case reports of autoimmune hepatitis{\textendash}like liver injury have been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We evaluated clinical features, treatment response and outcomes of liver injury following SARS-CoV-2 vaccination in a large case series. Approach and Results: We collected data from cases in 18 countries. The type of liver injury was assessed with the R-value. The study population was categorized according to features of immune-mediated hepatitis (positive autoantibodies and elevated immunoglobulin G levels) and corticosteroid therapy for the liver injury. We identified 87 patients (63\%, female), median age 48 (range: 18{\textendash}79) years at presentation. Liver injury was diagnosed a median 15 (range: 3{\textendash}65) days after vaccination. Fifty-one cases (59\%) were attributed to the Pfizer-BioNTech (BNT162b2) vaccine, 20 (23\%) cases to the Oxford-AstraZeneca (ChAdOX1 nCoV-19) vaccine and 16 (18\%) cases to the Moderna (mRNA-1273) vaccine. The liver injury was predominantly hepatocellular (84\%) and 57\% of patients showed features of immune-mediated hepatitis. Corticosteroids were given to 46 (53\%) patients, more often for grade 3{\textendash}4 liver injury than for grade 1{\textendash}2 liver injury (88.9\% vs. 43.5\%, p = 0.001) and more often for patients with than without immune-mediated hepatitis (71.1\% vs. 38.2\%, p = 0.003). All patients showed resolution of liver injury except for one man (1.1\%) who developed liver failure and underwent liver transplantation. Steroid therapy was withdrawn during the observation period in 12 (26\%) patients after complete biochemical resolution. None had a relapse during follow-up. Conclusions: SARS-CoV-2 vaccination can be associated with liver injury. Corticosteroid therapy may be beneficial in those with immune-mediated features or severe hepatitis. Outcome was generally favorable, but vaccine-associated liver injury led to fulminant liver failure in one patient.",

author = "Cumali Efe and Kulkarni, \{Anand V.\} and \{Terziroli Beretta-Piccoli\}, Benedetta and Bianca Magro and Albert St{\"a}ttermayer and Mustafa Cengiz and Daniel Clayton-Chubb and Craig Lammert and Christine Bernsmeier and {\"O}zlem G{\"u}l and \{la Tijera\}, \{Fatima Higuera de\} and Margarita Anders and Ellina Lytvyak and Mete Akın and Tugrul Purnak and Rodrigo Liberal and Mirta Peralta and Berat Ebik and Serkan Duman and Nurhan Demir and Yasemin Balaban and {\'A}lvaro Urzua and Fernando Contreras and Venturelli, \{Maria Grazia\} and Yılmaz Bilgi{\c c} and Adriana Medina and Marcos Girala and Fulya G{\"u}n{\c s}ar and Londo{\~n}o, \{Maria Carlota\} and Theodoros Androutsakos and Ayelen Kisch and Alper Yurci and Fatih G{\"u}zelbulut and {\c C}ağın, \{Yasir Furkan\} and Enver Avcı and Murat Akyıldız and Dindar-Demiray, \{Emine K{\"u}bra\} and Murat Harputluoğlu and Rahul Kumar and Satapathy, \{Sanjaya K.\} and Manuel Mendizabal and Marcelo Silva and Stefano Fagiuoli and Roberts, \{Stuart K.\} and Soylu, \{Ne{\c s}e Karadağ\} and Ramazan Idilman and Yoshida, \{Eric M.\} and Montano-Loza, \{Aldo J.\} and Dalekos, \{George N.\} and Ezequiel Ridruejo and Schiano, \{Thomas D.\} and Staffan Wahlin",

note = "Publisher Copyright: {\textcopyright} 2022 American Association for the Study of Liver Diseases.",

year = "2022",

month = dec,

doi = "10.1002/hep.32572",

language = "English",

volume = "76",

pages = "1576--1586",

journal = "Hepatology",

issn = "0270-9139",

publisher = "Lippincott Williams and Wilkins",

number = "6",

}

Efe, C, Kulkarni, AV, Terziroli Beretta-Piccoli, B, Magro, B, Stättermayer, A, Cengiz, M, Clayton-Chubb, D, Lammert, C, Bernsmeier, C, Gül, Ö, la Tijera, FHD, Anders, M, Lytvyak, E, Akın, M, Purnak, T, Liberal, R, Peralta, M, Ebik, B, Duman, S, Demir, N, Balaban, Y, Urzua, Á, Contreras, F, Venturelli, MG, Bilgiç, Y, Medina, A, Girala, M, Günşar, F, Londoño, MC, Androutsakos, T, Kisch, A, Yurci, A, Güzelbulut, F, Çağın, YF, Avcı, E, Akyıldız, M, Dindar-Demiray, EK, Harputluoğlu, M, Kumar, R, Satapathy, SK, Mendizabal, M, Silva, M, Fagiuoli, S, Roberts, SK, Soylu, NK, Idilman, R, Yoshida, EM, Montano-Loza, AJ, Dalekos, GN, Ridruejo, E, Schiano, TD & Wahlin, S 2022, 'Liver injury after SARS-CoV-2 vaccination: Features of immune-mediated hepatitis, role of corticosteroid therapy and outcome', Hepatology, vol. 76, no. 6, pp. 1576-1586. https://doi.org/10.1002/hep.32572

TY - JOUR

T1 - Liver injury after SARS-CoV-2 vaccination

T2 - Features of immune-mediated hepatitis, role of corticosteroid therapy and outcome

AU - Efe, Cumali

AU - Kulkarni, Anand V.

AU - Terziroli Beretta-Piccoli, Benedetta

AU - Magro, Bianca

AU - Stättermayer, Albert

AU - Cengiz, Mustafa

AU - Clayton-Chubb, Daniel

AU - Lammert, Craig

AU - Bernsmeier, Christine

AU - Gül, Özlem

AU - la Tijera, Fatima Higuera de

AU - Anders, Margarita

AU - Lytvyak, Ellina

AU - Akın, Mete

AU - Purnak, Tugrul

AU - Liberal, Rodrigo

AU - Peralta, Mirta

AU - Ebik, Berat

AU - Duman, Serkan

AU - Demir, Nurhan

AU - Balaban, Yasemin

AU - Urzua, Álvaro

AU - Contreras, Fernando

AU - Venturelli, Maria Grazia

AU - Bilgiç, Yılmaz

AU - Medina, Adriana

AU - Girala, Marcos

AU - Günşar, Fulya

AU - Londoño, Maria Carlota

AU - Androutsakos, Theodoros

AU - Kisch, Ayelen

AU - Yurci, Alper

AU - Güzelbulut, Fatih

AU - Çağın, Yasir Furkan

AU - Avcı, Enver

AU - Akyıldız, Murat

AU - Dindar-Demiray, Emine Kübra

AU - Harputluoğlu, Murat

AU - Kumar, Rahul

AU - Satapathy, Sanjaya K.

AU - Mendizabal, Manuel

AU - Silva, Marcelo

AU - Fagiuoli, Stefano

AU - Roberts, Stuart K.

AU - Soylu, Neşe Karadağ

AU - Idilman, Ramazan

AU - Yoshida, Eric M.

AU - Montano-Loza, Aldo J.

AU - Dalekos, George N.

AU - Ridruejo, Ezequiel

AU - Schiano, Thomas D.

AU - Wahlin, Staffan

PY - 2022/12

Y1 - 2022/12

N2 - Background and Aims: A few case reports of autoimmune hepatitis–like liver injury have been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We evaluated clinical features, treatment response and outcomes of liver injury following SARS-CoV-2 vaccination in a large case series. Approach and Results: We collected data from cases in 18 countries. The type of liver injury was assessed with the R-value. The study population was categorized according to features of immune-mediated hepatitis (positive autoantibodies and elevated immunoglobulin G levels) and corticosteroid therapy for the liver injury. We identified 87 patients (63%, female), median age 48 (range: 18–79) years at presentation. Liver injury was diagnosed a median 15 (range: 3–65) days after vaccination. Fifty-one cases (59%) were attributed to the Pfizer-BioNTech (BNT162b2) vaccine, 20 (23%) cases to the Oxford-AstraZeneca (ChAdOX1 nCoV-19) vaccine and 16 (18%) cases to the Moderna (mRNA-1273) vaccine. The liver injury was predominantly hepatocellular (84%) and 57% of patients showed features of immune-mediated hepatitis. Corticosteroids were given to 46 (53%) patients, more often for grade 3–4 liver injury than for grade 1–2 liver injury (88.9% vs. 43.5%, p = 0.001) and more often for patients with than without immune-mediated hepatitis (71.1% vs. 38.2%, p = 0.003). All patients showed resolution of liver injury except for one man (1.1%) who developed liver failure and underwent liver transplantation. Steroid therapy was withdrawn during the observation period in 12 (26%) patients after complete biochemical resolution. None had a relapse during follow-up. Conclusions: SARS-CoV-2 vaccination can be associated with liver injury. Corticosteroid therapy may be beneficial in those with immune-mediated features or severe hepatitis. Outcome was generally favorable, but vaccine-associated liver injury led to fulminant liver failure in one patient.

AB - Background and Aims: A few case reports of autoimmune hepatitis–like liver injury have been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We evaluated clinical features, treatment response and outcomes of liver injury following SARS-CoV-2 vaccination in a large case series. Approach and Results: We collected data from cases in 18 countries. The type of liver injury was assessed with the R-value. The study population was categorized according to features of immune-mediated hepatitis (positive autoantibodies and elevated immunoglobulin G levels) and corticosteroid therapy for the liver injury. We identified 87 patients (63%, female), median age 48 (range: 18–79) years at presentation. Liver injury was diagnosed a median 15 (range: 3–65) days after vaccination. Fifty-one cases (59%) were attributed to the Pfizer-BioNTech (BNT162b2) vaccine, 20 (23%) cases to the Oxford-AstraZeneca (ChAdOX1 nCoV-19) vaccine and 16 (18%) cases to the Moderna (mRNA-1273) vaccine. The liver injury was predominantly hepatocellular (84%) and 57% of patients showed features of immune-mediated hepatitis. Corticosteroids were given to 46 (53%) patients, more often for grade 3–4 liver injury than for grade 1–2 liver injury (88.9% vs. 43.5%, p = 0.001) and more often for patients with than without immune-mediated hepatitis (71.1% vs. 38.2%, p = 0.003). All patients showed resolution of liver injury except for one man (1.1%) who developed liver failure and underwent liver transplantation. Steroid therapy was withdrawn during the observation period in 12 (26%) patients after complete biochemical resolution. None had a relapse during follow-up. Conclusions: SARS-CoV-2 vaccination can be associated with liver injury. Corticosteroid therapy may be beneficial in those with immune-mediated features or severe hepatitis. Outcome was generally favorable, but vaccine-associated liver injury led to fulminant liver failure in one patient.

UR - https://www.scopus.com/pages/publications/85132426686

U2 - 10.1002/hep.32572

DO - 10.1002/hep.32572

M3 - Article

C2 - 35567545

AN - SCOPUS:85132426686

SN - 0270-9139

VL - 76

SP - 1576

EP - 1586

JO - Hepatology

JF - Hepatology

IS - 6

ER -

Liver injury after SARS-CoV-2 vaccination: Features of immune-mediated hepatitis, role of corticosteroid therapy and outcome

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