A. Ho, R. Orton, R. Tayler, P. Asamaphan, V. Herder, C. Davis, L. Tong, Katherine Smollett, Maria Manali, J. Allan, K. Rawlik, S. McDonald, Elen Vink, L. Pollock, Louise Gannon, C. Evans, J. McMenamin, K. Roy, K. Marsh, Titus Divala, M. Holden, M. Lockhart, D. Yirrell, S. Currie, M. O’Leary, David Henderson, S. Shepherd, C. Jackson, R. Gunson, A. Maclean, Neil McInnes, A. Bradley-Stewart, Richard Battle, J. Hollenbach, Paul Henderson, M. Odam, Primrose Chikowore, W. Oosthuyzen, M. Chand, M. S. Hamilton, D. Estrada-Rivadeneyra, Mike Levin, Nikos Avramidis, E. Pairo-Castineira, V. Vitart, C. Wilkie, Aubrey Jethro Myrsini Victoria Evangelos Claire Samuel Sa Cunnington Herberg Kaforou Wright Bellos Broderick, A. Cunnington, J. Herberg, M. Kaforou, Victoria J. Wright, Evangelos Bellos, Claire Broderick, S. Channon-Wells, S. Cooray, T. De, Giselle D'Souza, Leire Estramiana Elorrieta, R. Galassini, D. Habgood-Coote, Shea Hamilton, H. Jackson, James Kavanagh, M. M. Marjaneh, Stephanie Menikou, S. Nichols, R. Nijman, Harsita Patel, I. Pennisi, Oliver Powell, R. Reid, P. Shah, O. Vito, Elizabeth Whittaker, Clare Wilson, Rebecca S. Womersley, Amina Abdulla, S. Darnell, Sobia Mustafa, P. Georgiou, J. Manzano, Nicolas Moser, I. Pennisi, Michael J. Carter, S. Tibby, Jonathan Cohen, Francesca Davis, Julia Kenny, P. Wellman, Marie White, M. Fish, A. Jennings, M. Shankar-Hari, K. Fidler, Dr Agranoff, Vivien Richmond, Mathew Seal, Saul N. Faust, D. Owen, Ruth Ensom, Sarah Mckay, Diana Mondo, M. Shaji, R. Schranz, Prita Rughnani, Amutha Anpananthar, S. Liebeschuetz, A. Riddell, Nosheen Khalid, I. L. Malcolm, Teresa Simagan, M. Peters, A. Bamford, L. O'Neill, N. Pathan, E. Daubney, Deborah White, M. Heightman, S. Eisen, Terry Segal, L. Wellings, S. Drysdale, Nicole Branch, Lisa Hamzah, Heather 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, Mark Anthony, S. Hopton, Danielle Miller, Zoe J. Oliver, S. Beer, Bryony Ward, S. Shrestha, A. 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, José Gomez Rial, Pilar Leboráns Iglesias, N. Martinón-Torres, J. Sánchez, B. Pérez, J. Pardo-Seco, Lidia Piñeiro Rodríguez, S. Pischedda, Sara Rey Vázquez, I. R. Calle, C. Rodríguez-Tenreiro, L. Redondo-Collazo, Miguel Sadiki Ora, S. Fernández, Cristina Serén Trasorras, M. Iglesias, E. Carrol, E. Cocklin, A. Khanijau, Rebecca Lenihan, N. Lewis-Burke, Karen Newall, S. Romaine, M. Tsolia, Irini Eleftheriou, N. Spyridis, Maria Tambouratzi, Despoina N. Maritsi, A. Marmarinos, Marietta Xagorari, Lourida Panagiota, Pefanis Aggelos, Akinosoglou Karolina, Gogos Charalambos, Maragos Markos, Voulgarelis Michalis, Stergiou Ioanna, M. Emonts, E. Lim, John Isaacs, Kathryn Bell, Stephen Crulley, Daniel Fabian, E. Thomson, Diane Wallia, Caroline Miller, Ashley Bell, F. V. D. van der Velden, G. Shenton, Ashley Price, O. Treloar, Daisy Thomas, Pablo Rojo, C. Epalza, S. Villaverde, Sonia Márquez, M. Gijón, F. Machín, Laura Cabello, I. Hernández, Lourdes Gutiérrez, Ángela Manzanares, T. Kuijpers, M. van de Kuip, A. M. van Furth, J. M. van den Berg, Giske 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. De Luca, S. Chiurchiù, Martina Di Giuseppe, C. Vermont, H. Moll, D. Borensztajn, N. Hagedoorn, C. Tan, Joany M. Zachariasse, Medical students, W. Dik, C. Shen, D. Zavadska, S. Laivacuma, Aleksandra Rudzate, Diāna Stoldere, A. Barzdina, E. Bārzdiņa, Monta Madelāne, D. Grāvele, Dace Svile, R. Basmaci, N. Lachaume, Pauline Bories, Raja Ben Tkhayat, L. Chériaux, J. Davoust, K. Ong, M. Cotillon, Thibault de Groc, Sébastien D. Le, Nathalie Vergnault, Hélène Sée, Laure Cohen, Alice de Tugny, N. Danékova, M. Mommert-Tripon, Karen Brengel-Pesce, M. Pokorn, M. Kolnik, T. Avčin, Tanja Avramoska, N. Bahovec, P. Bogovič, L. Kitanovski, Mirijam Nahtigal, Lea Papst, T. Srovin, F. Strle, A. Srpčič, K. Vincek, M. van der Flier, Wim J. E. Tissing, R. W. Wösten-van Asperen, S. Vastert, Daniel Claes Vijlbrief, L. Bont, Tom F. W. Wolfs, Coco R. Beudeker, P. Agyeman, L. Schlapbach, Christoph Aebi, M. Usman, Stefanie Schlüchter, Verena Wyss, N. Schöbi, E. Zimmermann, Marion Meier, Kathrin Weber, P. Agyeman, L. Schlapbach, E. Giannoni, Martin Stocker, K. Posfay-Barbe, U. Heininger, Sara Bernhard-Stirnemann, A. Niederer-Loher, C. Kahlert, G. Natalucci, Christa Relly, T. Riedel, Christoph Aebi, C. Berger, Colin Fink, M. Voice, Leonides Calvo-Bado, M. Steele, J. Holden, B. Evans, J. Stevens, Peter Matthews, Kyle Billing, Werner Zenz, A. Binder, B. Kohlmaier, D. Kohlfürst, N. Schweintzger, Christoph J. Zurl, Susanne Hösele, Manuel Leitner, Lena Pölz, Alexandra Rusu, Glorija 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, S. Löffler, T. Niedrist, H. Pilch, Andreas Pfleger, K. Pfurtscheller, S. Rödl, A. Skrabl-Baumgartner, V. Strenger, Elmar Wallner, Dennie Tempel, D. van Keulen, Annelieke M. Strijbosch, M. Tauchert, U. von Both, L. Kolberg, Patricia Schmied, I. Alba-Alejandre, K. Danhauser, Nikolaus Haas, F. Hoffmann, M. Griese, T. Feuchtinger, S. Juranek, M. Kappler, E. Lurz, Esther Maier, K. Reiter, Carol Schoen, Sebastian Schroepf, Shunmay Yeung, Manuel Dewez, David Bath, Elizabeth J A Fitchett, F. Cresswell, S. Momodou, Effua Usuf, E. Ndure, K. Bojang, A. Roca, I. 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. D. Russell, D. Dorward, Maria Zambon, Richard S. Tedder, S. Khoo, L. Turtle, Tommy Solomon, Samreen Ijaz, Tom E. Fletcher, E. Thomson, NicholasS C. Price, J. Breuer, T. D. de Silva, C. Donohue, H. Hardwick, Lauren Obosi, S. Clohisey, Andrew Law, Lucy Norris, Sarah Tait, Murray Wham, R. Clark, A. Coutts, Lorna Donnelly, A. Fawkes, T. Gilchrist, K. Hafezi, Louise Macgillivray, A. Maclean, Sarah McCafferty, Kirstie Morrice, Lee Murphy, N. Wrobel, V. Shaw, K. Ahmed, Jane A. 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, Fiona McGill, C. Morris, John Morrice, D. Price, H. Reschreiter, Tim Reynolds, P. Whittaker, Thomas Jordan, R. Tayler, Clare Irving, Katherine Jack, M. Ramsay, Margaret W. Millar, Barry 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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30. 3. 2023.
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.