Feedback

Acute severe hepatitis outbreak in children: A perfect storm. What do we know, and what questions remain?

Affiliation
The Francis Crick Institute ,London ,United Kingdom
Matthews, Philippa C.;
Affiliation
Nuffield Department of Medicine ,University of Oxford ,Oxford ,England
Campbell, Cori;
Affiliation
Department of Infectious Diseases ,National Institute for Infectious Diseases-Prof. Dr. Matei Balş ,Carol Davila University of Medicine and Pharmacy ,Bucharest ,Romania
Săndulescu, Oana;
Affiliation
Faculty of Medicine ,Clinic for Infectious Diseases and Febrile Illnesses ,University Medical Centre Ljubljana ,University of Ljubljana ,Ljubljana ,Slovenia
Matičič, Mojca;
Affiliation
Virology Department ,Stefan S. Nicolau Institute of Virology ,“Carol Davila” University of Medicine and Pharmacy ,Bucharest ,Romania
Ruta, Simona Maria;
Affiliation
Hospital Universitario Reina Sofía ,Instituto Maimónides de Investigación Biomédica de Córdoba ,Universidad de Córdoba ,Córdoba ,Spain
Rivero-Juárez, Antonio;
Affiliation
Department of Internal Medicine and Infectious Diseases ,University Medical Centre Utrecht ,Utrecht ,Netherlands
van Welzen, Berend Joost;
Affiliation
INSERM U1052 ,Department of Intensive Care Unit ,Hôpital Lyon Sud ,Hospices Civils de Lyon ,Université Claude Bernard Lyon 1 ,Lyon ,France
Tan, Boun Kim;
Affiliation
Microbiology Department ,Instituto de Investigacion Ibs.Granada and Ciber de Enfermedades Infecciosas (CIBERINFEC) ,University Hospital San Cecilio ,Granada ,Spain
Garcia, Federico;
Affiliation
Department of Infectious Diseases ,“Dr. Victor Babes” Clinical Hospital of Infectious and Tropical Diseases ,Bucharest ,Romania
Gherlan, George Sebastian;
Affiliation
Department of Infectious Diseases and Clinical Microbiology ,Ankara University Faculty of Medicine ,Ankara ,Turkey
Çınar, Güle;
Affiliation
Department of Infectious Disease and Clinical Microbiology ,Ankara City Hospital ,Ankara Yıldırım Beyazıt University ,Ankara ,Turkey
Hasanoğlu, İmran;
Affiliation
Clinic for Infectious and Tropical Diseases ,University Clinical Center of Serbia ,Belgrade ,Serbia
Gmizić, Ivana;
Affiliation
Division of Infectious Diseases ,Ospedale Policlinico San Martino ,Genova ,Italy
Nicolini, Laura Ambra;
Affiliation
Nephrology and Infectious Diseases R&D ,Infectious Diseases Intensive Care Unit ,Faculty of Medicine of University of Porto ,Centro Hospitalar Universitário São João ,I3S - Instituto de Investigação e Inovaçãoem Saúde ,University of Porto ,Porto ,Portugal
Santos, Lurdes;
Affiliation
Ministry of Health ,National Centre for Infectious Diseases ,National Institute of Health ,Yerevan ,Armenia
Sargsyants, Narina;
Affiliation
Infectious Diseases Hospital Prof. Ivan Kirov and Department of Infectious Diseases ,Parasitology and Tropical Medicine ,Medical University of Sofia ,Sofia ,Bulgaria
Velikov, Petar;
Affiliation
Department of Microbiology ,Public Health Institute Novi Pazar ,Novi Pazar ,Serbia
Habibović, Selma;
Affiliation
Department of Virology ,INSERM ,Henri Mondor Hospital ,Assistance Publique-Hôpitaux de Paris ,Institut Mondor de Recherche Biomédicale ,Université Paris-Est ,Créteil ,France
Fourati, Slim;
Affiliation
Department of Immunological and Molecular Diagnostics ,University Hospital for Infectious Diseases “Dr Fran Mihaljevic” ,Zagreb ,Croatia
Židovec-Lepej, Snježana;
Affiliation
Medical Research Council-University of Glasgow Centre for Virus Research ,University of Glasgow ,Glasgow ,United Kingdom
Herder, Vanessa;
Affiliation
Department of Microbiology ,Oslo University Hospital ,Institute of Clinical Medicine ,University of Oslo ,Oslo ,Norway
Dudman, Susanne;
Affiliation
National Institute for Mother and Child Health “Alessandrescu-Rusescu” ,Carol Davila University of Medicine and Pharmacy ,Bucharest ,Romania
Miron, Victor Daniel;
Affiliation
NIHR Biomedical Research Centre ,Nottingham University Hospitals NHS Trust and the University of Nottingham ,Nottingham ,United Kingdom
Irving, William;
Affiliation
Department of Laboratory Medicine ,Section of Clinical Microbiology ,Region Skåne ,Lund ,Sweden
Şahin, Gülşen Özkaya

During the first half of 2022, the World Health Organization reported an outbreak of acute severe hepatitis of unknown aetiology (AS-Hep-UA) in children, following initial alerts from the United Kingdom (UK) where a cluster of cases was first observed in previously well children aged <6 years. Sporadic cases were then reported across Europe and worldwide, although in most countries incidence did not increase above the expected baseline. There were no consistent epidemiological links between cases, and microbiological investigations ruled out known infectious causes of hepatitis. In this review, we explore the evidence for the role of viral infection, superimposed on a specific host genetic background, as a trigger for liver pathology. This hypothesis is based on a high prevalence of Human Adenovirus (HAdV) 41F in affected children, together with metagenomic evidence of adeno-associated virus (Adeno-associated viruses)-2, which is a putative trigger for an immune-mediated liver injury. Roles for superantigen-mediated pathology have also been explored, with a focus on the potential contribution of SARS-CoV-2 infection. Affected children also had a high frequency of the MHC allele HLA-DRB1*04:01, supporting an immunological predisposition, and may have been vulnerable to viral coinfections due to disruption in normal patterns of exposure and immunity as a result of population lockdowns during the COVID-19 pandemic. We discuss areas of ongoing uncertainty, and highlight the need for ongoing scrutiny to inform clinical and public health interventions for this outbreak and for others that may evolve in future.

Cite

Citation style:
Could not load citation form.

Access Statistic

Total:
Downloads:
Abtractviews:
Last 12 Month:
Downloads:
Abtractviews:

Rights

License Holder: Copyright © 2022 Matthews, Campbell, Săndulescu, Matičič, Ruta, Rivero-Juárez, van Welzen, Tan, Garcia, Gherlan, Çınar, Hasanoğlu, Gmizić, Nicolini, Santos, Sargsyants, Velikov, Habibović, Fourati, Židovec-Lepej, Herder, Dudman, Miron, Irving and Şahin.

Use and reproduction: