Histological and serological features of acute liver injury after SARS-CoV-2 vaccination

Codoni, Greta; Kirchner, Theresa; Engel, Bastian; Villamil, Alejandra Maria; Efe, Cumali; Stättermayer, Albert Friedrich; Weltzsch, Jan Philipp; Sebode, Marcial; Bernsmeier, Christine; Lleo, Ana; Gevers, Tom JG.; Kupcinskas, Limas; Castiella, Agustin; Pinazo, Jose; De Martin, Eleonora; Bobis, Ingrid; Sandahl, Thomas Damgaard; Pedica, Federica; Invernizzi, Federica; Del Poggio, Paolo; Bruns, Tony; Kolev, Mirjam; Semmo, Nasser; Bessone, Fernando; Giguet, Baptiste; Poggi, Guido; Ueno, Masayuki; Jang, Helena; Elpek, Gülsüm Özlem; Soylu, Neşe Karadağ; Cerny, Andreas; Wedemeyer, Heiner; Vergani, Diego; Mieli Vergani, Giorgina; Lucena, M. Isabel; Andrade, Raul J.; Zen, Yoh; Taubert, Richard; Terziroli Beretta-Piccoli, Benedetta

doi:10.1016/j.jhepr.2022.100605

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Terziroli_2022_Elsevier_JHEP reports_Histological and serological features

Journal article

Histological and serological features of acute liver injury after SARS-CoV-2 vaccination

Codoni, Greta Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Kirchner, Theresa Dept. Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany - European Reference Network on Hepatological Diseases (ERN RARE-LIVER)
Engel, Bastian Dept. Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany - European Reference Network on Hepatological Diseases (ERN RARE-LIVER)
Villamil, Alejandra Maria ORCID HIBA, Buenos Aires, Argentina
Efe, Cumali Harran University, Şanlıurfa, Turkey
Stättermayer, Albert Friedrich ORCID Medical University of Vienna, Wien, Austria
Weltzsch, Jan Philipp I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany - European Reference Network on Hepatological Diseases (ERN RARE-LIVER)
Sebode, Marcial ORCID I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany - European Reference Network on Hepatological Diseases (ERN RARE-LIVER)
Bernsmeier, Christine ORCID University Centre for Gastrointestinal and Liver Diseases, Basel, Switzerland
Lleo, Ana ORCID IRCCS Humanitas Research Hospital Milan, Italy - Humanitas University, Pieve Emanuele, Milan, Italy
Gevers, Tom JG. ORCID European Reference Network on Hepatological Diseases (ERN RARE-LIVER) - Maastricht University Medical Center, Netherlands
Kupcinskas, Limas European Reference Network on Hepatological Diseases (ERN RARE-LIVER) - Lithuanian University of Health Sciences, Kaunas, Lituania
Castiella, Agustin Donostia University Hospital, Spain
Pinazo, Jose Servicios de Ap Digestivo y Farmacologia Clínica, Hospital Universitario Virgen de la Victoria, IBIMA, Universidad de Málaga, Spain
De Martin, Eleonora Hépatologie et Transplantation Hépatique, Hôpital Paul Brousse, Villejuif, France
Bobis, Ingrid Städtisches Krankenhaus Kiel, Germany
Sandahl, Thomas Damgaard ORCID Aarhus University Hospital, Denmark
Pedica, Federica ORCID Ospedale San Raffaele, Milano, Italy
Invernizzi, Federica Ospedale San Raffaele, Milano, Italy
Del Poggio, Paolo Policlinico San Marco, Zingonia, Italy
Bruns, Tony ORCID European Reference Network on Hepatological Diseases (ERN RARE-LIVER) - University Hospital RWTH Aachen, Germany
Kolev, Mirjam ORCID Hepatology, University Clinic for Visceral Surgery and Medicine, Inselspital Bern, University of Bern, Switzerland
Semmo, Nasser Hepatology, University Clinic for Visceral Surgery and Medicine, Inselspital Bern, University of Bern, Switzerland
Bessone, Fernando ORCID University of Rosario School of Medicine, Rosario, Argentina
Giguet, Baptiste Centre Hospitalier Universitaire de Rennes, France
Poggi, Guido Istituti Clinici Pavia-Vigevano UO Epatologia Oncologica, Vigevano, Italy
Ueno, Masayuki ORCID Department of Gastroenterology and Hepatology, Kurashiki Central Hospital, Japan - Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Japan
Jang, Helena Department of Clinical Immunology and Allergy, Royal North Shore Hospital, St Leonards, Australia
Elpek, Gülsüm Özlem ORCID Department of Pathology, Akdeniz University Faculty of Medicine, Antalya, Turkey
Soylu, Neşe Karadağ Department of Pathology, Inonu University Faculty of Medicine, Malatya, Turkey
Cerny, Andreas Epatocentro Ticino, Lugano, Switzerland
Wedemeyer, Heiner Dept. Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany - European Reference Network on Hepatological Diseases (ERN RARE-LIVER)
Vergani, Diego MowatLabs, Faculty of Life Sciences & Medicine, King’s College London, King’s College Hospital, London, United Kingdom
Mieli Vergani, Giorgina MowatLabs, Faculty of Life Sciences & Medicine, King’s College London, King’s College Hospital, London, United Kingdom
Lucena, M. Isabel ORCID Servicios de Ap Digestivo y Farmacologia Clínica, Hospital Universitario Virgen de la Victoria, IBIMA, Universidad de Málaga, Spain - Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
Andrade, Raul J. Servicios de Ap Digestivo y Farmacologia Clínica, Hospital Universitario Virgen de la Victoria, IBIMA, Universidad de Málaga, Spain - Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
Zen, Yoh MowatLabs, Faculty of Life Sciences & Medicine, King’s College London, King’s College Hospital, London, United Kingdom
Taubert, Richard Dept. Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany - European Reference Network on Hepatological Diseases (ERN RARE-LIVER)
Terziroli Beretta-Piccoli, Benedetta ORCID Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Epatocentro Ticino, Lugano, Switzerland - MowatLabs, Faculty of Life Sciences & Medicine, King’s College London, King’s College Hospital, London, United Kingdom

2023

Published in:

JHEP reports. - 2023, vol. 5, no. 1, p. 100605

English Background & Aims: Liver injury with autoimmune features after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is increasingly reported. We investigated a large international cohort of individuals with acute hepatitis arising after SARS-CoV-2 vaccination, focusing on histological and serological features. Methods: Individuals without known pre-existing liver diseases and transaminase levels ≥5x the upper limit of normal within 3 months after any anti-SARS-CoV-2 vaccine, and available liver biopsy were included. Fifty-nine patients were recruited; 35 females; median age 54 years. They were exposed to various combinations of mRNA, vectorial, inactivated and protein-based vaccines. Results: Liver histology showed predominantly lobular hepatitis in 45 (76%), predominantly portal hepatitis in 10 (17%), and other patterns in four (7%) cases; seven had fibrosis Ishak stage ≥3, associated with more severe interface hepatitis. Autoimmune serology, centrally tested in 31 cases, sh wed anti-antinuclear antibody in 23 (74%), anti-smooth muscle antibody in 19 (61%), anti-gastric parietal cells in eight (26%), anti-liver kidney microsomal antibody in four (13%), and anti-mitochondrial antibody in four (13%) cases. Ninety-one percent were treated with steroids ± azathioprine. Serum transaminase levels improved in all cases and were normal in 24/58 (41%) after 3 months, and in 30/46 (65%) after 6 months. One patient required liver transplantation. Of 15 patients re-exposed to SARS-CoV-2 vaccines, three relapsed. Conclusion: Acute liver injury arising after SARS-CoV-2 vaccination is frequently associated with lobular hepatitis and positive autoantibodies. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. A close follow-up is warranted to assess the long-term outcomes of this condition. Impact and implications: Cases of liver injury after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have been published. We investigated a large international cohort of individuals with acute hepatitis after SARS-CoV-2 vaccination, focusing on liver biopsy findings and autoantibodies: liver biopsy frequently shows inflammation of the lobule, which is typical of recent injury, and autoantibodies are frequently positive. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. Close follow-up is warranted to assess the long-term outcome of this condition.

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