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 2023 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. application/pdf https://susi.usi.ch/global/documents/331234 https://n2t.net/ark:/12658/srd1331234 https://susi.usi.ch/documents/331234/files/Terziroli_2022_Elsevier_JHEP reports_Histological and serological features.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jhepr.2022.100605 info:eu-repo/semantics/altIdentifier/ark/12658/srd1331234 info:eu-repo/semantics/openAccess CC BY JHEP reports. - 2023, vol. 5, no. 1, p. 100605 Acute liver injury SARS-CoV-2 vaccines Liver histology Autoimmune liver serology info:eu-repo/classification/udc/61 Histological and serological features of acute liver injury after SARS-CoV-2 vaccination http://purl.org/coar/resource_type/c_6501