TY  - JOUR
AU  - Röttele, Felix
AU  - Zollner, Andreas
AU  - Mogler, Carolin
AU  - Yuksel, Muhammed
AU  - Arikan, Cigdem
AU  - Karl, Vivien
AU  - Aberle, Judith Helene
AU  - Aberle, Stephan W
AU  - Kogler, Hubert
AU  - Vécsei, Andreas
AU  - Vodopiutz, Julia
AU  - Salié, Henrike
AU  - Gräser, Anne
AU  - Krimmel, Laurenz
AU  - Martin, Pius
AU  - Lurz, Eberhard
AU  - Maier, Felix Immanuel
AU  - Woelfle, Lena
AU  - Nobre, Susana
AU  - Goncalves, Isabel
AU  - Kern, Lisa
AU  - Schwemmle, Martin
AU  - Boettler, Tobias
AU  - Hofmann, Maike
AU  - Hasselblatt, Peter
AU  - Thimme, Robert
AU  - Tilg, Herbert
AU  - Müller, Thomas
AU  - Vogel, Georg Friedrich
AU  - Bengsch, Bertram
TI  - 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.
JO  - Gut
VL  - 74
IS  - 9
SN  - 0017-5749
CY  - London
PB  - BMJ Publishing Group
M1  - DKFZ-2025-00718
SP  - 1486-1499
PY  - 2025
N1  - 2025 Aug 7;74(9):1486-1499
AB  - 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.
KW  - ACUTE HEPATITIS (Other)
KW  - COVID-19 (Other)
KW  - IMMUNOHISTOPATHOLOGY (Other)
KW  - PAEDIATRIC HEPATOLOGY (Other)
KW  - T LYMPHOCYTES (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40187893
DO  - DOI:10.1136/gutjnl-2024-333880
UR  - https://inrepo02.dkfz.de/record/300265
ER  -