Codoni, GretaGretaCodoniKirchner, TheresaTheresaKirchnerEngel, BastianBastianEngelVillamil, Alejandra MariaAlejandra MariaVillamilEfe, CumaliCumaliEfeStättermayer, Albert FriedrichAlbert FriedrichStättermayerWeltzsch, Jan PhilippJan PhilippWeltzschSebode, MarcialMarcialSebodeBernsmeier, ChristineChristineBernsmeierLleo, AnaAnaLleoGevers, Tom JgTom JgGeversKupčinskas, LimasLimasKupčinskasCastiella, AgustinAgustinCastiellaPinazo, JoseJosePinazoDe Martin, EleonoraEleonoraDe MartinBobis, IngridIngridBobisSandahl, Thomas DamgaardThomas DamgaardSandahlPedica, FedericaFedericaPedicaInvernizzi, FedericaFedericaInvernizziDel Poggio, PaoloPaoloDel PoggioBruns, TonyTonyBrunsKolev, MirjamMirjamKolev0000-0002-5027-3432Semmo, NasserNasserSemmoBessone, FernandoFernandoBessoneGiguet, BaptisteBaptisteGiguetPoggi, GuidoGuidoPoggiUeno, MasayukiMasayukiUenoJang, HelenaHelenaJangElpek, Gülsüm ÖzlemGülsüm ÖzlemElpekSoylu, Neşe KaradağNeşe KaradağSoyluCerny, AndreasAndreasCernyWedemeyer, HeinerHeinerWedemeyerVergani, DiegoDiegoVerganiMieli-Vergani, GiorginaGiorginaMieli-VerganiLucena, M IsabelM IsabelLucenaAndrade, Raul JRaul JAndradeZen, YohYohZenTaubert, RichardRichardTaubertTerziroli Beretta-Piccoli, BenedettaBenedettaTerziroli Beretta-Piccoli2024-10-142024-10-142023-01https://boris-portal.unibe.ch/handle/20.500.12422/115687BACKGROUND & 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, showed 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.enAIHautoimmune hepatitis ALPalkaline phosphatase ALTalanine aminotransferase AMAanti-mitochondrial antibody ANAanti-nuclear antibody ASTaspartate aminotransferase COVID-19coronavirus disease 2019 DILIdrug-induced liver injury IAIHGInternational Autoimmune Hepatitis Group IFTindirect immunofluorescence LKMliver kidney microsomal LTliver transplantation PCAparietal cell antigen SARS-CoV-2 vaccines SARS-CoV-2severe acute respiratory syndrome coronavirus type 2 SLAsoluble liver antigen SMAanti-smooth muscle antibody ULNupper limit of normal acute liver injury autoimmune liver serology liver histology pIgGpolyreactive IgG600 - Technology::610 - Medicine & healtharticle10.48350/1752583644025910.1016/j.jhepr.2022.100605