Antonia Ho, Richard Orton, Rachel Tayler, P. Asamaphan, V. Herder, Chris Davis, Lily Tong, Katherine Smollett, Maria Manali, J. Allan, K. Rawlik, Sarah E. McDonald, Elen Vink, L. Pollock, Louise Gannon, Clair Evans, J. McMenamin, Kirsty Roy, K. Marsh, Titus Divala, Matthew T. G. Holden, Michael Lockhart, D. Yirrell, Sandra Currie, M. O’Leary, David Henderson, S. Shepherd, C. Jackson, R. Gunson, A. Maclean, Neil McInnes, A. Bradley-Stewart, Richard Battle, Jill A. Hollenbach, Paul Henderson, M. Odam, Primrose Chikowore, W. Oosthuyzen, Meera A Chand, M. S. Hamilton, D. Estrada-Rivadeneyra, Mike Levin, Nikos Avramidis, E. Pairo-Castineira, V. Vitart, Craig Wilkie, Aubrey Jethro Myrsini Victoria Evangelos Claire Samuel Sa Cunnington Herberg Kaforou Wright Bellos Broderick, Aubrey Cunnington, J. Herberg, M. Kaforou, Victoria Wright, Evangelos Bellos, Claire Broderick, S. Channon-Wells, S. Cooray, Tisham 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, Ivana Pennisi, Oliver Powell, R. Reid, P. Shah, O. Vito, Elizabeth Whittaker, Clare Wilson, Rebecca S. Womersley, Amina Abdulla, S. Darnell, Sobia Mustafa, Pantelis Georgiou, J. Manzano, Nicolas Moser, Ivana Pennisi, Michael J. Carter, Shane M Tibby, Jonathan Cohen, Francesca Davis, Julia Kenny, P. Wellman, Marie White, M. Fish, Aislinn Jennings, M. Shankar-Hari, Katy 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, Lauran O’Neill, N. Pathan, E. Daubney, Deborah White, Melissa 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, 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, Sanjeev M. 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, Sara Rey Vázquez, 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, Despoina N Maritsi, Antonios 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. V. 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, M. Di Giuseppe, C. Vermont, Henriette A Moll, D. Borensztajn, N. Hagedoorn, Chantal D. Tan, Joany M. Zachariasse, Medical students, W. Dik, C. Shen, D. Zavadska, S. Laivacuma, Aleksandra Rudzāte, 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, Kim-Thanh 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, 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, Louis J. Bont, Tom F. W. Wolfs, Coco R Beudeker, Philipp Agyeman, L. Schlapbach, Christoph Aebi, M. Usman, Stefanie Schlüchter, Verena Wyss, Nina Schöbi, E. Zimmermann, Marion Meier, Kathrin Weber, Philipp Agyeman, L. Schlapbach, E. Giannoni, Martin Stocker, K. Posfay-Barbe, U. Heininger, Sara Bernhard-Stirnemann, A. Niederer-Loher, Christian Kahlert, G. Natalucci, Christa Relly, Thomas Riedel, Christoph Aebi, Christoph Berger, Colin Fink, M. Voice, Leonides Calvo-Bado, Michael Steele, Jennifer Holden, B. Evans, J. Stevens, Peter Matthews, Kyle Billing, Werner Zenz, A. Binder, B. Kohlmaier, Daniela S. Kohlfürst, N. Schweintzger, Christoph J. Zurl, Susanne Hösele, Manuel Leitner, Lena Pölz, Alexandra Rusu, G. Rajic, Bianca Stoiser, Martina Strempfl, M. Sagmeister, S. Bauchinger, Martin Benesch, Astrid Ceolotto, Ernst Eber, S. Gallistl, H. Haidl, A. Hauer, Christa Hude, Andreas Kapper, Markus Keldorfer, Sabine Löffler, T. Niedrist, H. Pilch, A. Pfleger, K. Pfurtscheller, Siegfried Rödl, A. Skrabl-Baumgartner, V. Strenger, Elmar Wallner, Dennie Tempel, Daniëlle van Keulen, Annelieke M. Strijbosch, M. Tauchert, U. von Both, Laura Kolberg, Patricia Schmied, I. Alba-Alejandre, Katharina Danhauser, Nikolaus Haas, Florian 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, Fiona 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, Clark D Russell, David Dorward, Maria Zambon, Richard S. Tedder, S. Khoo, L. Turtle, Tommy Solomon, Samreen Ijaz, Tom Fletcher, E. Thomson, NicholasS . C. Price, Judith 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, L. Macgillivray, Alan Maclean, Sarah McCafferty, K. Morrice, L. 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, Rachel Tayler, Clare Irving, Katherine Jack, M. Ramsay, Margaret W. Millar, Barry Milligan, Naomi 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
6
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.