A. Ho, R. Orton, Rachel Tayler, P. Asamaphan, V. Herder, Chris Davis, Lily Tong, Katherine Smollett, Maria Manali, Jay Allan, K. Rawlik, Sarah E. McDonald, Elen Vink, L. Pollock, Louise Gannon, C. Evans, J. McMenamin, K. Roy, K. Marsh, T. Divala, M. Holden, M. Lockhart, D. Yirrell, S. Currie, M. O'Leary, David R F Henderson, S. Shepherd, C. Jackson, R. Gunson, A. Maclean, N. McInnes, A. Bradley-Stewart, R. Battle, J. Hollenbach, Paul Henderson, M. Odam, Primrose Chikowore, W. Oosthuyzen, M. Chand, M. S. Hamilton, D. Estrada-Rivadeneyra, M. Levin, Nikos Avramidis, E. Pairo-Castineira, V. Vitart, Craig Wilkie, Aubrey Jethro Myrsini Victoria Evangelos Claire Samuel Sa Cunnington Herberg Kaforou Wright Bellos Broderick, A. Cunnington, J. Herberg, M. Kaforou, Victoria Wright, Evangelos Bellos, C. Broderick, S. Channon-Wells, S. Cooray, Tisham De, Giselle D'Souza, Leire Estramiana Elorrieta, R. Galassini, D. Habgood-Coote, Shea Hamilton, H. Jackson, J. Kavanagh, M. M. Marjaneh, Stephanie Menikou, S. Nichols, R. Nijman, Harsita Patel, Ivana Pennisi, Oliver Powell, R. Reid, P. Shah, O. Vito, E. Whittaker, Clare Wilson, R. Womersley, Amina Abdulla, S. Darnell, Sobia Mustafa, P. Georgiou, J. Manzano, Nicolas Moser, Ivana Pennisi, Michael Carter, S. Tibby, Jonathan Cohen, Francesca Davis, J. Kenny, P. Wellman, M. White, M. Fish, Aislinn Jennings, M. Shankar-Hari, K. Fidler, D. Agranoff, V. Richmond, Mathew 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, Ivone Lancoma Malcolm, Teresa Simagan, M. Peters, A. Bamford, Lauran O’Neill, N. Pathan, Esther 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, S. Neshat, Barney Scholefield, C. Robbins, H. Winmill, S. Paulus, Andrew J. Pollard, Mark Anthony, S. Hopton, Danielle Miller, Zoe J. Oliver, S. Beer, Bryony Ward, S. Shrestha, Andrew J. Pollard, M. Gurung, P. Amatya, B. Pokhrel, S. Bijukchhe, Timothy Lubinda, Sarah Kelly, P. O'reilly, F. Martinón-Torres, Antonio Salas, Fernando A. González, Xabier Bello, Mirian Ben 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, A. Khanijau, Rebecca Lenihan, N. Lewis-Burke, Karen Newall, S. Romaine, M. Tsolia, Irini Eleftheriou, N. Spyridis, Maria Tambouratzi, D. Maritsi, A. 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, Diane Wallia, 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, A. M. V. van Furth, J. M. van den Berg, G. Biesbroek, F. Verkuil, C. van der Zee, D. Pajkrt, M. V. van Hensbroek, D. Schonenberg, M. Gruppen, S. Nagelkerke, Machiel H. Jansen, Ines Goetschalckx, L. Romani, M. De Luca, S. Chiurchiù, M. Di Giuseppe, C. Vermont, H. Moll, D. Borensztajn, N. Hagedoorn, Chantal D. Tan, Joany M. Zachariasse, Medical students, W. Dik, Ching-Fen Shen, D. Zavadska, S. Laivacuma, Aleksandra Rudzāte, Diāna Stoldere, A. Bārzdiņa, E. Barzdina, Monta Madelāne, D. Grāvele, Dace Svile, R. Basmaci, N. Lachaume, Pauline Bories, R. B. Tkhayat, L. Chériaux, Juraté Davoust, K. Ong, M. Cotillon, Thibault de Groc, Sébastien D. 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, Philipp Agyeman, L. Schlapbach, Christoph Aebi, M. Usman, Stefanie Schlüchter, Verena Wyss, N. Schöbi, E. Zimmermann, Marion Meier, Kathrin Weber, Philipp Agyeman, L. Schlapbach, E. Giannoni, M. Stocker, K. Posfay‐Barbe, U. Heininger, Sara Bernhard-Stirnemann, A. Niederer-Loher, C. Kahlert, G. Natalucci, C. Relly, T. Riedel, Christoph Aebi, C. Berger, Colin G Fink, M. Voice, L. Calvo-Bado, Michael Steele, J. Holden, 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, M. 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, S. Momodou, Effua Usuf, E. Ndure, K. Bojang, A. Roca, Isatou Sarr, Malcolm G. Gail Peter J. M. Jake Laura Clark D. David Mari Semple Carson Openshaw Dunning Merson Russell Dorw, M. Semple, G. Carson, P. Openshaw, J. Dunning, L. Merson, C. Russell, David Dorward, M. Zambon, R. Tedder, S. Khoo, L. Turtle, Tommy Solomon, S. Ijaz, T. Fletcher, E. Thomson, NicholasS . C. Price, Judith Breuer, T. D. de Silva, C. Donohue, H. Hardwick, Lauren Obosi, S. Clohisey, Andrew Law, L. Norris, Sarah Tait, Murray Wham, R. Clark, A. Coutts, Lorna Donnelly, A. Fawkes, T. Gilchrist, K. Hafezi, L. Macgillivray, Alan Maclean, Sarah McCafferty, K. Morrice, L. Murphy, N. Wrobel, V. Shaw, K. Ahmed, J. Armstrong, Lauren Lett, Paul Henderson, L. Pollock, S. Kishore, H. Brotherton, L. Armstrong, A. Mitra, A. Dall, K. Bohmova, Sheena Logan, Louise Gannon, K. Agwuh, S. Chukkambotla, I. DuRand, D. Fullerton, Sanjeev Gar, Clive Graham, T. Grammatikopoulos, S. Hartshorn, L. Hodgson, P. Jennings, G. Koshy, T. Leiner, James Limb, J. Little, Sheena Logan, E. Matovu, F. McGill, C. Morris, J. Morrice, D. Price, H. Reschreiter, Tim Reynolds, P. Whittaker, T. Jordan, Rachel Tayler, C. Irving, Katherine Jack, M. Ramsay, Margaret W. Millar, B. Milligan, N. Hickey, M. Connon, C. Ward, L. Beveridge, S. MacFarlane, K. Leitch, Claire Bell, L. Finlayson, J. Dawson, J. Candlish, L. McGenily, Tara Roome, Cynthia Diaba
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19. 7. 2022.
Adeno-associated virus 2 infection in children with non-A–E hepatitis
An outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland^ 1 in April 2022 and has now been identified in 35 countries^ 2 . Several recent studies have suggested an association with human adenovirus with this outbreak, a virus not commonly associated with hepatitis. Here we report a detailed case–control investigation and find an association between adeno-associated virus 2 (AAV2) infection and host genetics in disease susceptibility. Using next-generation sequencing, PCR with reverse transcription, serology and in situ hybridization, we detected recent infection with AAV2 in plasma and liver samples in 26 out of 32 (81%) cases of hepatitis compared with 5 out of 74 (7%) of samples from unaffected individuals. Furthermore, AAV2 was detected within ballooned hepatocytes alongside a prominent T cell infiltrate in liver biopsy samples. In keeping with a CD4^+ T-cell-mediated immune pathology, the human leukocyte antigen (HLA) class II HLA-DRB1*04:01 allele was identified in 25 out of 27 cases (93%) compared with a background frequency of 10 out of 64 (16%; P = 5.49 × 10^−12). In summary, we report an outbreak of acute paediatric hepatitis associated with AAV2 infection (most likely acquired as a co-infection with human adenovirus that is usually required as a ‘helper virus’ to support AAV2 replication) and disease susceptibility related to HLA class II status. A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.