Morphologic and molecular analysis of liver injury after SARS-CoV-2 vaccination reveals distinct characteristics.

Humans COVID-19 Vaccines / adverse effects Hepatitis, Autoimmune SARS-CoV-2 Chemical and Drug Induced Liver Injury, Chronic COVID-19 / prevention & control Liver / pathology Receptors, Antigen, T-Cell Vaccination
Autoimmune hepatitis COVID-19 Drug-induced liver injury SARS-CoV-2 Vaccination

Journal

Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886

Informations de publication

Date de publication:
09 2023
Historique:
received: 17 08 2022
revised: 10 05 2023
accepted: 19 05 2023
medline: 22 8 2023
pubmed: 9 6 2023
entrez: 8 6 2023
Statut: ppublish

Résumé

Liver injury after COVID-19 vaccination is very rare and shows clinical and histomorphological similarities with autoimmune hepatitis (AIH). Little is known about the pathophysiology of COVID-19 vaccine-induced liver injury (VILI) and its relationship to AIH. Therefore, we compared VILI with AIH. Formalin-fixed and paraffin-embedded liver biopsy samples from patients with VILI (n = 6) and from patients with an initial diagnosis of AIH (n = 9) were included. Both cohorts were compared by histomorphological evaluation, whole-transcriptome and spatial transcriptome sequencing, multiplex immunofluorescence, and immune repertoire sequencing. Histomorphology was similar in both cohorts but showed more pronounced centrilobular necrosis in VILI. Gene expression profiling showed that mitochondrial metabolism and oxidative stress-related pathways were more and interferon response pathways were less enriched in VILI. Multiplex analysis revealed that inflammation in VILI was dominated by CD8 Our analyses support that SARS-CoV-2 VILI is related to AIH but also shows distinct differences from AIH in histomorphology, pathway activation, cellular immune infiltrates, and TCR usage. Therefore, VILI may be a separate entity, which is distinct from AIH and more closely related to drug-induced autoimmune-like hepatitis. Little is known about the pathophysiology of COVID-19 vaccine-induced liver injury (VILI). Our analysis shows that COVID-19 VILI shares some similarities with autoimmune hepatitis, but also has distinct differences such as increased activation of metabolic pathways, a more prominent CD8+ T cell infiltrate, and an oligoclonal T and B cell response. Our findings suggest that VILI is a distinct disease entity. Therefore, there is a good chance that many patients with COVID-19 VILI will recover completely and will not develop long-term autoimmune hepatitis.

Sections du résumé

BACKGROUND & AIMS
Liver injury after COVID-19 vaccination is very rare and shows clinical and histomorphological similarities with autoimmune hepatitis (AIH). Little is known about the pathophysiology of COVID-19 vaccine-induced liver injury (VILI) and its relationship to AIH. Therefore, we compared VILI with AIH.
METHODS
Formalin-fixed and paraffin-embedded liver biopsy samples from patients with VILI (n = 6) and from patients with an initial diagnosis of AIH (n = 9) were included. Both cohorts were compared by histomorphological evaluation, whole-transcriptome and spatial transcriptome sequencing, multiplex immunofluorescence, and immune repertoire sequencing.
RESULTS
Histomorphology was similar in both cohorts but showed more pronounced centrilobular necrosis in VILI. Gene expression profiling showed that mitochondrial metabolism and oxidative stress-related pathways were more and interferon response pathways were less enriched in VILI. Multiplex analysis revealed that inflammation in VILI was dominated by CD8
CONCLUSIONS
Our analyses support that SARS-CoV-2 VILI is related to AIH but also shows distinct differences from AIH in histomorphology, pathway activation, cellular immune infiltrates, and TCR usage. Therefore, VILI may be a separate entity, which is distinct from AIH and more closely related to drug-induced autoimmune-like hepatitis.
IMPACT AND IMPLICATIONS
Little is known about the pathophysiology of COVID-19 vaccine-induced liver injury (VILI). Our analysis shows that COVID-19 VILI shares some similarities with autoimmune hepatitis, but also has distinct differences such as increased activation of metabolic pathways, a more prominent CD8+ T cell infiltrate, and an oligoclonal T and B cell response. Our findings suggest that VILI is a distinct disease entity. Therefore, there is a good chance that many patients with COVID-19 VILI will recover completely and will not develop long-term autoimmune hepatitis.

Identifiants

DOI: 10.1016/j.jhep.2023.05.020 PMID: 37290592 PMC: PMC10245467
pubmed: 37290592
pii: S0168-8278(23)00348-3
doi: 10.1016/j.jhep.2023.05.020
pmc: PMC10245467
pii:
doi:

Substances chimiques

COVID-19 Vaccines 0
Receptors, Antigen, T-Cell 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

666-676

Subventions

Organisme : NIAID NIH HHS
ID : DP2 AI171139
Pays : United States

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.

Auteurs

Sarp Uzun (S)

Institute of Pathology, University Hospital Basel, Basel, Switzerland.

Carl P Zinner (CP)

Institute of Pathology, University Hospital Basel, Basel, Switzerland.

Amke C Beenen (AC)

Institute of Pathology, University Hospital Basel, Basel, Switzerland.

Ilaria Alborelli (I)

Institute of Pathology, University Hospital Basel, Basel, Switzerland.

Ewelina M Bartoszek (EM)

Microscopy Core Facility, Department of Biomedicine, University of Basel, Basel, Switzerland.

Jason Yeung (J)

Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Byron Calgua (B)

Institute of Pathology, University Hospital Basel, Basel, Switzerland.

Matthias Reinscheid (M)

Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany.

Peter Bronsert (P)

Institute for Surgical Pathology, Freiburg University Medical Center, University of Freiburg, Freiburg, Germany; Core Facility for Histopathology and Digital Pathology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Anna K Stalder (AK)

Institute of Pathology, University Hospital Basel, Basel, Switzerland.

Jasmin D Haslbauer (JD)

Institute of Pathology, University Hospital Basel, Basel, Switzerland.

Juerg Vosbeck (J)

Institute of Pathology, University Hospital Basel, Basel, Switzerland.

Luca Mazzucchelli (L)

Istituto Cantonale di Patologia, Locarno, Switzerland.

Tobias Hoffmann (T)

Innere Medizin, Spital Dornach, Dornach, Switzerland.

Luigi M Terracciano (LM)

Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.

Gregor Hutter (G)

Brain Tumor Immunotherapy Lab, Department of Biomedicine, University of Basel, Basel, Switzerland; Department of Neurosurgery, University Hospital Basel, Basel, Switzerland.

Michael Manz (M)

Gastroenterology and Hepatology, University Centre for Gastrointestinal and Liver Diseases Basel, Switzerland.

Isabelle Panne (I)

Gastroenterology and Hepatology, University Centre for Gastrointestinal and Liver Diseases Basel, Switzerland.

Tobias Boettler (T)

Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Maike Hofmann (M)

Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Bertram Bengsch (B)

Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany; Partner Site Freiburg, German Cancer Consortium (DKTK), Heidelberg, Germany.

Markus H Heim (MH)

Gastroenterology and Hepatology, University Centre for Gastrointestinal and Liver Diseases Basel, Switzerland; Department of Biomedicine, University of Basel, Switzerland.

Christine Bernsmeier (C)

Gastroenterology and Hepatology, University Centre for Gastrointestinal and Liver Diseases Basel, Switzerland; Department of Biomedicine, University of Basel, Switzerland.

Sizun Jiang (S)

Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Pathology, Dana Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Alexandar Tzankov (A)

Institute of Pathology, University Hospital Basel, Basel, Switzerland.

Benedetta Terziroli Beretta-Piccoli (B)

Faculty of Biomedical Sciences, Università Della Svizzera Italiana, Lugano, Switzerland; Epatocentro Ticino, Lugano, Switzerland; MowatLabs, Faculty of Life Sciences and Medicine, King's College London, King's College Hospital, London, UK.

Matthias S Matter (MS)

Institute of Pathology, University Hospital Basel, Basel, Switzerland. Electronic address: matthias.matter@usb.ch.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Morphologic and molecular analysis of liver...
questionsmedicales.fr › Mélanges complexes › Produits biologiques › Vaccins › Vaccins antiviraux › Vaccins contre la COVID-19 › Morphologic and molecular analysis of liver...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Hépatite auto-immune › Morphologic and molecular analysis of liver...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › Virus du SRAS › SARS-CoV-2 › Morphologic and molecular analysis of liver...
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questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › Morphologic and molecular analysis of liver...
questionsmedicales.fr › Système digestif › Foie › Morphologic and molecular analysis of liver...
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