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@ARTICLE{Rttele:300265,
      author       = {F. Röttele and A. Zollner and C. Mogler and M. Yuksel and
                      C. Arikan and V. Karl and J. H. Aberle and S. W. Aberle and
                      H. Kogler and A. Vécsei and J. Vodopiutz and H. Salié and
                      A. Gräser and L. Krimmel and P. Martin and E. Lurz and F.
                      I. Maier and L. Woelfle and S. Nobre and I. Goncalves and L.
                      Kern and M. Schwemmle and T. Boettler and M. Hofmann and P.
                      Hasselblatt and R. Thimme and H. Tilg and T. Müller and G.
                      F. Vogel and B. Bengsch$^*$},
      title        = {{C}haracteristic immune cell interactions in livers of
                      children with acute hepatitis revealed by spatial
                      single-cell analysis identify a possible postacute sequel of
                      {COVID}-19.},
      journal      = {Gut},
      volume       = {74},
      number       = {9},
      issn         = {0017-5749},
      address      = {London},
      publisher    = {BMJ Publishing Group},
      reportid     = {DKFZ-2025-00718},
      pages        = {1486-1499},
      year         = {2025},
      note         = {2025 Aug 7;74(9):1486-1499},
      abstract     = {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.},
      keywords     = {ACUTE HEPATITIS (Other) / COVID-19 (Other) /
                      IMMUNOHISTOPATHOLOGY (Other) / PAEDIATRIC HEPATOLOGY (Other)
                      / T LYMPHOCYTES (Other)},
      cin          = {FR01},
      ddc          = {610},
      cid          = {I:(DE-He78)FR01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40187893},
      doi          = {10.1136/gutjnl-2024-333880},
      url          = {https://inrepo02.dkfz.de/record/300265},
}