%0 Journal Article
%A Röttele, Felix
%A Zollner, Andreas
%A Mogler, Carolin
%A Yuksel, Muhammed
%A Arikan, Cigdem
%A Karl, Vivien
%A Aberle, Judith Helene
%A Aberle, Stephan W
%A Kogler, Hubert
%A Vécsei, Andreas
%A Vodopiutz, Julia
%A Salié, Henrike
%A Gräser, Anne
%A Krimmel, Laurenz
%A Martin, Pius
%A Lurz, Eberhard
%A Maier, Felix Immanuel
%A Woelfle, Lena
%A Nobre, Susana
%A Goncalves, Isabel
%A Kern, Lisa
%A Schwemmle, Martin
%A Boettler, Tobias
%A Hofmann, Maike
%A Hasselblatt, Peter
%A Thimme, Robert
%A Tilg, Herbert
%A Müller, Thomas
%A Vogel, Georg Friedrich
%A Bengsch, Bertram
%T Characteristic immune cell interactions in livers of children with acute hepatitis revealed by spatial single-cell analysis identify a possible postacute sequel of COVID-19.
%J Gut
%V 74
%N 9
%@ 0017-5749
%C London
%I BMJ Publishing Group
%M DKFZ-2025-00718
%P 1486-1499
%D 2025
%Z 2025 Aug 7;74(9):1486-1499
%X A rise in paediatric cases of acute hepatitis of unknown origin (AHUO) was observed in 2022, some requiring liver transplantation. A link to adeno-associated virus 2 infection and CD4+T-cell mediated disease was reported in cohorts in the UK and USA but does not explain all cases.To determine the intrahepatic immune cell interactions in the inflamed liver and a possible contribution of SARS-CoV-2 infection.Patients with acute non-A non-E hepatitis (10/12 AHUO, 2/12 subacute) during February 2022-December 2022 undergoing liver biopsy were recruited in a European patient cohort. Hepatological, virological, histopathological and highly multiplexed spatial and single-cell analyses of liver biopsies were performed.Patients were negative for adenoviral and SARS-CoV-2 PCR. Three patients had a positive adenoviral serology and 10/12 patients had a history or serological evidence of SARS-CoV-2 infection. Imaging mass cytometry identified significant intrahepatic immune infiltration with an enrichment of CD8+T-cells. The highest CD8 infiltration and concomitant peripheral immune activation were observed in patients with the most severe hepatitis. CD8+T-cell infiltration was connected to histomorphological interface hepatitis and bridging necrosis. Cellular neighbourhood analysis indicated disease-associated microanatomic interactions between CX3CR1+ endothelial and myeloid cell populations, interacting with effector CD8+T-cells suggesting a pathogenic cellular triad. Of note, we detected intrahepatic SARS-CoV-2 antigens in ACE2-expressing cells in the areas with significant pathology in 11/12 samples using several different detection methods. 10/12 patients were treated with corticosteroid therapy and no liver transplantation was required.We identified a possible manifestation of an immune-mediated postacute sequel to COVID-19 associated with a characteristic immune infiltrate in children with AHUO. COVID-19 testing should be considered in paediatric AHUO.
%K ACUTE HEPATITIS (Other)
%K COVID-19 (Other)
%K IMMUNOHISTOPATHOLOGY (Other)
%K PAEDIATRIC HEPATOLOGY (Other)
%K T LYMPHOCYTES (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40187893
%R 10.1136/gutjnl-2024-333880
%U https://inrepo02.dkfz.de/record/300265