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Sofia Morfopoulou, Sarah Buddle, O. E. Torres Montaguth, Laura Atkinson, J. A. Guerra-Assunção, Mahdi Moradi Marjaneh, Riccardo Zennezini Chiozzi, N. Storey, Luis Campos, J. C. Hutchinson, J. Counsell, G. Pollara, Sunando Roy, C. Venturini, Juan F. Antinao Diaz, Ala’a Siam, Luke J. Tappouni, Zeinab Asgarian, J. Ng, Killian S. Hanlon, Alexander Lennon, A. McArdle, Agata Czap, J. Rosenheim, Catarina Andrade, Glenn Anderson, Jack C. D. Lee, Rachel J. Williams, Charlotte Williams, H. Tutill, N. Bayzid, Luz Marina Martin Bernal, Hannah Macpherson, Kylie Montgomery, C. Moore, K. Templeton, C. Neill, M. Holden, R. Gunson, S. Shepherd, P. Shah, S. Cooray, M. Voice, Michael Steele, Colin G Fink, T. Whittaker, G. Santilli, P. Gissen, B. Kaufer, J. Reich, J. Andreani, P. Simmonds, Dimah K. Alrabiah, S. Castellano, Primrose Chikowore, M. Odam, Tommy Rampling, C. Houlihan, K. Hoschler, Tiina Talts, C. Celma, Suam Gonzalez, E. Gallagher, R. Simmons, C. Watson, S. Mandal, M. Zambon, M. Chand, J. Hatcher, S. De, K. Baillie, M. Semple, Evangelos Claire Samuel Tisham Giselle Leire Estramiana Dieg Bellos Broderick Channon-Wells De D’Souza Elorriet, Evangelos Bellos, C. Broderick, S. Channon-Wells, Tisham De, Giselle D'Souza, Leire Estramiana Elorrieta, D. Estrada-Rivadeneyra, R. Galassini, D. Habgood-Coote, Shea Hamilton, H. Jackson, J. Kavanagh, M. M. Marjaneh, Stephanie Menikou, S. Nichols, R. Nijman, Harsita Patel, I. Pennisi, Oliver Powell, R. Reid, O. Vito, E. Whittaker, Clare Wilson, R. Womersley, Amina Abdulla, S. Darnell, Sobia Mustafa, P. Georgiou, J. Manzano, Nicolas Moser, Michael J. Carter, S. Tibby, Jonathan Cohen, Francesca Davis, J. Kenny, P. Wellman, Marie K White, M. Fish, Aislinn Jennings, Shankar-Hari, K. Fidler, D. Agranoff, V. Richmond, M. Seal, S. Faust, D. Owen, Ruth Ensom, Sarah McKay, Diana Mondo, M. Shaji, R. Schranz, Prita Rughnani, A. Anpananthar, S. Liebeschuetz, A. Riddell, Nosheen Khalid, I. L. Malcolm, Teresa Simagan, M. Peters, A. Bamford, N. Pathan, E. Daubney, D. White, M. Heightman, S. Eisen, T. Segal, L. Wellings, S. Drysdale, N. Branch, Lisa Hamzah, H. Jarman, M. Nyirenda, Lisa Capozzi, E. Gardiner, R. Moots, M. Nasher, A. Hanson, Michelle Linforth, S. O’Riordan, Donna Ellis, Akash Deep, I. Caro, F. Shackley, A. Bellini, S. Gormley, Samira Neshat, Barnaby J. Scholefield, C. Robbins, H. Winmill, S. Paulus, A. Pollard, S. Hopton, Danielle Miller, Zoe J. Oliver, S. Beer, B. Ward, S. Shrestha, M. Gurung, P. Amatya, B. Pokhrel, Sanjeev M. Bijukchhe, Timothy Lubinda, Sarah Kelly, P. O'reilly, F. Martinón-Torres, Antonio Salas, Fernando A. González, Xabier Bello, M. García, Sandra Carnota, M. Cebey-López, M. Currás-Tuala, Carlos Durán Suárez, Luisa García Vicente, A. Gómez-Carballa, Jose Gómez Rial, Pilar Leboráns Iglesias, N. Martinón-Torres, J. Sánchez, B. Pérez, J. Pardo-Seco, Lidia Piñeiro Rodríguez, S. Pischedda, S. Vazquez, I. R. Calle, C. Rodríguez-Tenreiro, L. Redondo-Collazo, M. Ora, S. Fernández, Cristina Serén Trasorras, M. Iglesias, E. Carrol, Elizabeth Cocklin, Aakash Khanijau, Rebecca Lenihan, N. Lewis-Burke, Karen Newal, S. Romaine, M. Tsolia, Irini Eleftheriou, N. Spyridis, Maria Tambouratzi, D. Maritsi, Antonios Marmarinos, Marietta Xagorari, Lourida Panagiota, Pefanis Aggelos, Akinosoglou Karolina, Gogos Charalambos, Maragos Markos, Voulgarelis Michalis, Stergiou Ioanna, M. Emonts, E. Lim, J. Isaacs, K. Bell, Stephen Crulley, Daniel Fabian, E. Thomson, C. Miller, Ashley Bell, F. V. D. van der Velden, G. Shenton, Ashley Price, O. Treloar, Daisy Thomas, P. Rojo, C. Epalza, S. Villaverde, Sonia Márquez, M. Gijón, F. Machín, Laura Cabello, I. Hernández, Lourdes Gutiérrez, Á. Manzanares, T. Kuijpers, M. van de Kuip, Marceline Tutu van Furth, M. J. van den Berg, G. Biesbroek, F. Verkuil, C. W. van der Zee, D. Pajkrt, M. V. van Hensbroek, D. Schonenberg, M. Gruppen, S. Nagelkerke, Machiel H. Jansen, Ines Goetschalckx, L. Romani, M. D. Luca, S. Chiurchiù, Martina Di Giuseppe, C. Vermont, H. Moll, D. Borensztajn, N. Hagedoorn, Chantal D. Tan, Joany M. Zachariasse, W. Dik, Ching-Fen Shen, D. Zavadska, S. Laivacuma, Aleksandra Rudzate, Diāna Stoldere, A. Barzdina, E. Barzdina, Monta Madelāne, D. Grāvele, Dace Svile, R. Basmaci, Noémie Lachaume, Pauline Bories, R. B. Tkhayat, L. Chériaux, Juraté Davoust, K. Ong, M. Cotillon, Thibault de Groc, Sébastien Le, Nathalie Vergnault, H. Sée, Laure Cohen, Alice de Tugny, N. Danékova, M. Mommert-Tripon, K. Brengel-Pesce, M. Pokorn, M. Kolnik, T. Avčin, Tanja Avramoska, N. Bahovec, Petra Bogovič, L. Kitanovski, Mirijam Nahtigal, Lea Papst, T. Srovin, F. Strle, Ana Srpčič, K. Vincek, M. van der Flier, Wim J. E. Tissing, R. W. Wösten-van Asperen, S. Vastert, Daniel Claes Vijlbrief, L. Bont, T. Wolfs, Coco R Beudeker, P. Agyeman, L. Schlapbach, C. Aebi, M. Usman, Stefanie Schlüchter, Verena Wyss, Nina Schöbi, E. Zimmermann, Kathrin Weber, E. Giannoni, M. Stocker, K. Posfay-Barbe, U. Heininger, Sara Bernhard-Stirnemann, A. Niederer-Loher, C. Kahlert, G. Natalucci, C. Relly, T. Riedel, C. Berger, J. Holden, L. Calvo-Bado, B. Evans, J. Stevens, P. Matthews, Kyle Billing, W. Zenz, A. Binder, B. Kohlmaier, Daniela S. Kohlfürst, N. Schweintzger, Christoph J. Zurl, Susanne Hösele, Manuel Leitner, Lena Pölz, A. Rusu, G. Rajic, Bianca Stoiser, Martina Strempfl, M. Sagmeister, S. Bauchinger, Martin Benesch, Astrid Ceolotto, E. Eber, S. Gallistl, H. Haidl, A. Hauer, Christa Hude, Andreas Kapper, Markus Keldorfer, Sabine Löffler, T. Niedrist, H. Pilch, A. Pfleger, K. Pfurtscheller, S. Rödl, A. Skrabl-Baumgartner, V. Strenger, Elmar Wallner, D. Tempel, Daniëlle van Keulen, Annelieke M. Strijbosch, M. Tauchert, U. von Both, Laura Kolberg, Patricia Schmied, I. Alba-Alejandre, K. Danhauser, N. Haas, F. Hoffmann, M. Griese, T. Feuchtinger, S. Juranek, M. Kappler, E. Lurz, E. Maier, K. Reiter, Carol Schoen, Sebastian Schroepf, S. Yeung, Manuel Dewez, David Bath, Elizabeth J A Fitchett, F. Cresswell, Aubrey Jethro Mysini Victoria Lucas Clive Sara Ian Naomi Cunnington Herberg Kaforou Wright Baumard Hoggart , A. Cunnington, J. Herberg, M. Kaforou, V. Wright, Lucas R. Baumard, C. Hoggart, Sara Hourmat, I. Maconochie, Naomi Lin, Ivonne Pena Paz, Ladan Ali, Rikke Jorgensen, S. Persand, Molly M. Stevens, Eun-Ji Kim, Benjamin Pierce, J. Dudley, Emma Tavliavini, Ching-Chuan Liu, Shih-Min Wang, C. B. Farto, R. Barral-Arca, María B Castro, A. Balode, Dārta Deksne, I. Grope, Anija Meiere, Ieva Nokalna, J. Pavare, Z. Pučuka, Katrīna Selecka, Aleksandra A. Sidorova, U. Urbāne, Effua Usuf, K. Bojang, Syed M. A. Zaman, F. Secka, S. Anderson, A. Sarr, M. Saidykhan, Saffiatou Darboe, Samba Ceesay, Umberto D'Alessandro, L. Schlapbach, S. Paulus, Rebecca Jennings, Joann A. Johnston, Simon Leigh, Karen Newall, A. Marmarinos, Kelly Syggelou, Hinrich Baumgart, Martin Benesch, G. Gores, Larissa Krenn, Gudrun Nordberg, M. Sperl, Laura Stampfer, H. Till, Andreas Trobisch, J. E. Dewez, Martin Hibberd, A. Miners, R. Nijman, Catherine Wedderburn, Anne Meierford, B. Leurent, R. de Groot, M. van der Flier, M. D. de Jonge, K. V. van Aerde, W. Alkema, B. van den Broek, J. Gloerich, A. V. van Gool, S. Henriet, M. Huijnen, R. Philipsen, Esther Willems, G. Gerrits, M. van Leur, J. Heidema, L. de Haan, C. Miedema, C. Neeleman, C. Obihara, G. Tramper-Stranders, R. Kandasamy, S. Paulus, Michael J. Carter, D. O’Connor, S. Bibi, D. Kelly
96 30. 3. 2023.

Genomic investigations of unexplained acute hepatitis in children

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology. Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK^ 1 . Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children.


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