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

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

doi:10.1002/hep.32572

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

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Author(s): Cumali Efe ¹ ^, , Anand V. Kulkarni ² , Benedetta Terziroli Beretta‐Piccoli ³ ^, ⁴ , Bianca Magro ⁵ , Albert Friedrich Stättermayer ⁶ , Mustafa Cengiz ⁷ , Daniel Clayton‐Chubb ⁸ , Craig Lammert ⁹ , Christine Bernsmeier ¹⁰ ^, ¹¹ , Özlem Gül ¹² , Fatima Higuera‐de la Tijera ¹³ , Margarita Anders ¹⁴ , Ellina Lytvyak ¹⁵ , Mete Akın ¹⁶ , Tugrul Purnak ¹⁷ , Rodrigo Liberal ¹⁸ ^, ¹⁹ , Mirta Peralta ²⁰ ^, ²¹ , Berat Ebik ²² , Serkan Duman ²³ , Nurhan Demir ²⁴ , Yasemin Balaban ²⁵ , Álvaro Urzua ²⁶ , Fernando Contreras ²⁷ , Maria Grazia Venturelli ²⁸ , Yılmaz Bilgiç ²⁹ , Adriana Medina ³⁰ , Marcos Girala ³⁰ , Fulya Günşar ³¹ , Maria‐Carlota Londoño ³² , Theodoros Androutsakos ³³ , Ayelen Kisch ³⁴ , Alper Yurci ³⁵ , Fatih Güzelbulut ³⁶ , Yasir Furkan Çağın ²⁹ , Enver Avcı ³⁷ , Murat Akyıldız ³⁸ , Emine Kübra Dindar‐Demiray ³⁹ , Murat Harputluoğlu ²⁹ , Rahul Kumar ⁴⁰ , Sanjaya K. Satapathy ⁴¹ , Manuel Mendizabal ²¹ ^, ⁴² , Marcelo Silva ²¹ ^, ⁴² , Stefano Fagiuoli ⁵ , Stuart K. Roberts ⁸ ^, ⁴³ , Neşe Karadağ Soylu ⁴⁴ , Ramazan Idilman ²³ , Eric M. Yoshida ⁴⁵ , Aldo J. Montano‐Loza ¹⁵ , George N. Dalekos ⁴⁶ ^, ⁴⁷ , Ezequiel Ridruejo ²¹ ^, ⁴² ^, ⁴⁸ , Thomas D. Schiano ⁴⁹ , Staffan Wahlin ⁵⁰

Publication date (Electronic): 23 June 2022

Journal: Hepatology (Baltimore, Md.)

Publisher: John Wiley and Sons Inc.

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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.

Abstract

SARS‐COV‐2 vaccination and liver injury.

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Most cited references 36

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Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Chaolin Huang, Yeming Wang, Xingwang Li … (2020)

Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.

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Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention

Zunyou Wu, Jennifer M. McGoogan (2020)

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COVID-19 vaccines: modes of immune activation and future challenges

John Teijaro, Donna Farber (2021)

The new vaccines against SARS-CoV-2 are novel in terms of specificity, their wide dissemination across the global population and the inclusion of newly licensed mRNA platforms. We discuss here how the approved vaccines trigger innate immunity to promote durable immunological memory and consider the future implications of protecting populations with these vaccines.

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Author and article information

Contributors

Cumali Efe: scumaliefe@gmail.com

Journal

Journal ID (nlm-ta): Hepatology

Journal ID (iso-abbrev): Hepatology

Journal ID (doi): 10.1002/(ISSN)1527-3350

Journal ID (publisher-id): HEP

Title: Hepatology (Baltimore, Md.)

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Print): 0270-9139

ISSN (Electronic): 1527-3350

Publication date (Electronic): 23 June 2022

Publication date PMC-release: 23 June 2022

Electronic Location Identifier: 10.1002/hep.32572

Affiliations

[ ¹ ] Department of Gastroenterology Harran University Hospital Şanlıurfa Turkey

[ ² ] Department of Hepatology and Liver Transplantation Asian Institute of Gastroenterology Hospitals Hyderabad India

[ ³ ] Faculty of Biomedical Sciences Università Della Svizzera Italiana Lugano Switzerland

[ ⁴ ] Epatocentro Ticino Lugano Switzerland

[ ⁵ ] Gastroenterology Hepatology and Transplantation ASST Papa Giovanni XXIII‐Bergamo Bergamo Italy

[ ⁶ ] Division of Gastroenterology and Hepatology Department of Internal Medicine III Medical University of Vienna Vienna Austria

[ ⁷ ] Department of Gastroenterology Gülhane Training and Research Hospital Ankara Turkey

[ ⁸ ] Department of Gastroenterology Alfred Health Melbourne Victoria Australia

[ ⁹ ] Department of Medicine Indiana University School of Medicine Indianapolis Indiana USA

[ ¹⁰ ] Department of Biomedicine University of Basel Basel Switzerland

[ ¹¹ ] University Centre for Gastrointestinal and Liver Diseases Basel Switzerland

[ ¹² ] Department of Gastroenterology Kırıkkale University Kırıkkale Turkey

[ ¹³ ] Gastroenterology and Hepatology Unit Hospital General de México Ciudad de México Mexico

[ ¹⁴ ] Hepatology and Liver Transplant Unit Hospital Alemán Ciudad Autónoma de Buenos Aires Argentina

[ ¹⁵ ] Division of Gastroenterology and Liver Unit University of Alberta Edmonton Alberta Canada

[ ¹⁶ ] Department of Gastroenterology Akdeniz University Faculty of Medicine Antalya Turkey

[ ¹⁷ ] Division of Gastroenterology Hepatology and Nutrition McGovern Medical School Houston Texas USA

[ ¹⁸ ] Gastroenterology and Hepatology Department Centro Hospitalar e Universitário de São João Porto Portugal

[ ¹⁹ ] World Gastroenterology Organization (WGO) Porto Training Center Porto Portugal

[ ²⁰ ] Hepatology Section Hospital Francisco J Muñiz Ciudad Autónoma de Buenos Aires Argentina

[ ²¹ ] Latin American Liver Research Educational and Awareness Network (LALREAN) Pilar Argentina

[ ²² ] Department of Gastroenterology Gazi Yaşargil Education and Research Hospital Diyarbakir Turkey

[ ²³ ] Department of Gastroenterology Ankara University Medical Faculty Ankara Turkey

[ ²⁴ ] Department of Gastroenterology Haseki Training and Research Hospital Istanbul Turkey

[ ²⁵ ] Department of Gastroenterology Faculty of Medicine Hacettepe University Ankara Turkey

[ ²⁶ ] Gastroenterology and Hepatology Unit Hospital Clínico Universidad de Chile Santiago de Chile Chile

[ ²⁷ ] Centro de Gastroenterología Avanzada Santa Dominco Dominican Republic

[ ²⁸ ] Gastroenterology and Hepatology Unit Clinica Stella Maris Lima Peru

[ ²⁹ ] Department of Gastroenterology Inönü University School of Medicine Malatya Turkey

[ ³⁰ ] Gastroenterology and Hepatology Unit Hospital de Clínicas, Universidad Nacional de Asunción San Lorenzo Paraguay

[ ³¹ ] Department of Gastroenterology Ege University School of Medicine İzmir Turkey

[ ³² ] Liver Unit Hospital Clínic Barcelona IDIBAPS CIBERehd Barcelona Spain

[ ³³ ] Department of Pathophysiology National and Kapodistrian University of Athens Medical School Athens Greece

[ ³⁴ ] Hepatology Section Hospital Bonorino Udaondo Ciudad Autónoma de Buenos Aires Argentina

[ ³⁵ ] Department of Gastroenterology Erciyes University School of Medicine Kayseri Turkey

[ ³⁶ ] Department of Gastroenterology Haydarpaşa Numune Education and Research Hospital İstanbul Turkey

[ ³⁷ ] Department of Gastroenterology KTO Karatay University Medical School Affiliated Konya Medicana Hospital Konya Turkey

[ ³⁸ ] Department of Gastroenterology Koc University School of Medicine Istanbul Turkey

[ ³⁹ ] Department of Infectious Diseases and Clinical Microbiology Bitlis Tatvan State Hospital Bitlis Turkey

[ ⁴⁰ ] Department of Gastroenterology and Hepatology Changi General Hospital Medicine Academic Clinical Programme Sing Health Duke‐NUS Academic Medical Centre Singapore

[ ⁴¹ ] Department of Internal Medicine Donald and Barbara Zucker School of Medicine Northwell Health Manhasset New York USA

[ ⁴² ] Hepatology and Liver Transplant Unit Hospital Universitario Austral Pilar Argentina

[ ⁴³ ] Central Clinical School Department of Medicine Monash University Melbourne Victoria Australia

[ ⁴⁴ ] Department of Pathology Inönü University Faculty of Medicine Malatya Turkey

[ ⁴⁵ ] Division of Gastroenterology University of British Columbia and Vancouver General Hospital Vancouver British Columbia Canada

[ ⁴⁶ ] Department of Medicine and Research Laboratory of Internal Medicine National Expertise Center of Greece in Autoimmune Liver Diseases General University Hospital of Larissa Larissa Greece

[ ⁴⁷ ] European Reference Network on Hepatological Diseases (ERN RARE‐LIVER) General University Hospital of Larissa Larissa Greece

[ ⁴⁸ ] Hepatology Section Department of Medicine Centro de Educación Médica e Investigaciones Clínicas, CEMIC Ciudad Autónoma de Buenos Aires Argentina

[ ⁴⁹ ] Division of Liver Diseases the Mount Sinai Medical Center New York New York USA

[ ⁵⁰ ] Hepatology Division, Department of Upper GI Diseases Karolinska Institutet and Karolinska University Hospital Stockholm Sweden

Author notes

[*] [* ] Correspondence

Cumali Efe, Department of Gastroenterology, Harran University Hospital, Şanlıurfa, Turkey.

Email: scumaliefe@ 123456gmail.com

[Correction added June 29, 2022 after first online publication: Author names were corrected for "Fatih Güzelbulut" and ''Murat Akyıldız." Stefano Fagiuoli's affiliation was incorrectly listed and updated.]

Author information

Anand V. Kulkarni https://orcid.org/0000-0002-1240-1675

Benedetta Terziroli Beretta‐Piccoli https://orcid.org/0000-0001-5004-5029

Bianca Magro https://orcid.org/0000-0002-6417-3205

Daniel Clayton‐Chubb https://orcid.org/0000-0001-7479-9669

Craig Lammert https://orcid.org/0000-0003-3809-640X

Yasemin Balaban https://orcid.org/0000-0002-0901-9192

Álvaro Urzua https://orcid.org/0000-0002-8059-8844

Maria‐Carlota Londoño https://orcid.org/0000-0002-6533-1586

Theodoros Androutsakos https://orcid.org/0000-0003-2556-6230

Rahul Kumar https://orcid.org/0000-0002-5092-4821

Sanjaya K. Satapathy https://orcid.org/0000-0003-0153-2829

Manuel Mendizabal https://orcid.org/0000-0002-7026-9908

Stuart K. Roberts https://orcid.org/0000-0002-9015-7997

Ezequiel Ridruejo https://orcid.org/0000-0002-3321-0683

Article

Publisher ID: HEP32572 Other ID: HEP-22-0461.R3

DOI: 10.1002/hep.32572

PMC ID: 9348326

PubMed ID: 35567545

SO-VID: c7c3abbc-eb9d-494d-b66b-ea89d109bd2e

License:

This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

History

Date revision received : 04 May 2022

Date received : 28 February 2022

Date accepted : 05 May 2022

Page count

Figures: 1, Tables: 3, Pages: 11, Words: 5906

Custom metadata

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details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.7 mode:remove_FC converted:03.08.2022

ScienceOpen disciplines: Gastroenterology & Hepatology

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ScienceOpen disciplines: Gastroenterology & Hepatology

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