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World J Virol. Mar 25, 2023; 12(2): 100-108
Published online Mar 25, 2023. doi: 10.5501/wjv.v12.i2.100
Immune-mediated liver injury following COVID-19 vaccination
Georgios Schinas, Eleni Polyzou, Vasiliki Dimakopoulou, Stamatia Tsoupra, Charalambos Gogos, Karolina Akinosoglou
Georgios Schinas, Department of Medicine, University of Patras, Patras 26504, Greece
Eleni Polyzou, Vasiliki Dimakopoulou, Stamatia Tsoupra, Charalambos Gogos, Karolina Akinosoglou, Department of Internal Medicine, University of Patras, Patras 26504, Greece
Author contributions: Akinosoglou K and Gogos C conceived the idea; Schinas G performed the literature search, reviewed data, and wrote the manuscript; Polyzou E, Dimakopoulou V, and Tsoupra S performed the literature search and reviewed data; Akinosoglou K and Gogos C critically corrected the manuscript; Akinosoglou K revised the manuscript
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Karolina Akinosoglou, MD, PhD, Associate Professor, Department of Internal Medicine, University of Patras, 5th floor, University General Hospital of Patras, Patras 26504, Greece.
Received: October 11, 2022
Peer-review started: October 11, 2022
First decision: November 15, 2022
Revised: November 23, 2022
Accepted: January 23, 2023
Article in press: January 23, 2023
Published online: March 25, 2023

Liver injury secondary to vaccination is a rare adverse event that has recently come under attention thanks to the continuous pharmacovigilance following the widespread implementation of coronavirus disease 2019 (COVID-19) vaccination protocols. All three most widely distributed severe acute respiratory syndrome coronavirus 2 vaccine formulations, e.g., BNT162b2, mRNA-1273, and ChAdOx1-S, can induce liver injury that may involve immune-mediated pathways and result in autoimmune hepatitis-like presentation that may require therapeutic intervention in the form of corticosteroid administration. Various mechanisms have been proposed in an attempt to highlight immune checkpoint inhibition and thus establish causality with vaccination. The autoimmune features of such a reaction also prompt an in-depth investigation of the newly employed vaccine technologies. Novel vaccine delivery platforms, e.g., mRNA-containing lipid nanoparticles and adenoviral vectors, contribute to the inflammatory background that leads to an exaggerated immune response, while patterns of molecular mimicry between the spike (S) protein and prominent liver antigens may account for the autoimmune presentation. Immune mediators triggered by vaccination or vaccine ingredients per se, including autoreactive antibodies, cytokines, and cytotoxic T-cell populations, may inflict hepatocellular damage through well-established pathways. We aim to review available data associated with immune-mediated liver injury associated with COVID-19 vaccination and elucidate potential mechanisms underlying its pathogenesis.

Keywords: Adverse effects, COVID-19 vaccines, mRNA vaccine, Autoimmune Hepatitis, Chemical and Drug Induced Liver Injury, Autoimmunity

Core Tip: Following the worldwide implementation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination protocols, several reports suggest an increase in the occurrence of autoimmune phenomena involving the liver. Studies on vaccine-induced liver injury point to a specific pattern of hepatocellular injury that involves immune-mediated pathways. This minireview explores the underlying pathophysiology of immune-mediated liver injury following SARS-CoV-2 vaccination and examines the most widely distributed vaccine formulations’ autoimmune and hepatotoxic potential.