@article{Morfopoulou_S-2022_90980,
title = {Genomic investigations of acute hepatitis of unknown aetiology in children},
author = {Morfopoulou, S. and Buddle, S. and Montaguth, O. and Atkinson, L. and Assuncao, J. and Storey, N. and Roy, S. and Lennon, A. and Lee, J. and Williams, R. and Williams, C. and Tutill, H. and Bayzid, N. and Bernal, L. and Moore, C. and Templeton, K. and Neill, C. and Holden, M. and Gunson, R. and Shepherd, S. and Shah, P. and Cooray, S. and Voice, M. and Steele, M. and Fink, C. and Whittaker, T. and Santilli, G. and Gissen, P. and Brown, R. and Kaufer, B. and Reich, J. and Andreani, J. and Simmonds, P. and Alrabiah, D. and Hereza, S. and DIAMONDS and PERFORM Consortia and Andrade, C. and Anderson, G. and Kelgeri, C. and Waddington, S. and Diaz, J. and Hatcher, J. and De, S. and Chiozzi, R. and Thalassinos, K. and Jacques, T. and Talts, T. and Hoschler, K. and Celma, C. and Gonzalez, S. and Gallagher, E. and Simmons, R. and Watson, C. and Mandal, S. and Zambon, M. and Chand, M. and Campos, L. and Martin, J. and Thomson, E. and Ushiro-Lumb, I. and Levin, M. and Brown, J. and Breuer, J.},
month = {jul},
year = {2022},
abstract = {Since the first reports of hepatitis of unknown aetiology occurring in UK children, over 1000 cases have been reported worldwide, including 268 cases in the UK, with the majority younger than 6 years old. Using genomic, proteomic  and immunohistochemical methods, we undertook extensive investigation of 28 cases and 136 control subjects. In five cases who underwent liver  transplantation, we detected high levels of adeno-associated virus 2 (AAV2) in the explanted livers. AAV2 was also detected at high levels in blood from 10/11 nontransplanted cases. Low levels of Adenovirus (HAdV) and Human Herpesvirus 6B (HHV6B), both of which enable AAV2 lytic replication, were  also found in the five explanted livers and blood from 15/17 and 6/9  respectively, of the 23 non-transplant cases tested. In contrast, AAV2 was detected at low titre in 6/100 whole bloods from child controls from cohorts with presence or absence of hepatitis and/or adenovirus infection. Our data show an association of AAV2 at high titre in blood or liver tissue, with unexplained  hepatitis in children infected in the recent HAdV-F41 outbreak. We were unable to find evidence by electron microscopy, immunohistochemistry or proteomics of HAdV or AAV2 viral particles or proteins in explanted livers, suggesting that hepatic pathology is not due to direct lytic infection by either virus. The potential that AAV2, although not previously associated with disease, may, together with HAdV-F41 and/or HHV-6, be causally implicated in the outbreak of unexplained hepatitis, requires further investigation.},
journal = {medRxiv},
publisher = {medRxiv},
url = {https://doi.org/10.1101/2022.07.28.22277963},
}
