ReviewFrontiers in pharmacology2022
Acute severe hepatitis outbreak in children: A perfect storm. What do we know, and what questions remain?
Review in Frontiers in pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 2 syntheses or guidelines pooled it, 33 citations in OpenAlex.
- A systematic review on the incidence of influenza viruses in wastewater matrices: Implications for public health.PloS one · 2024Pooled it
- Pooled it
- Traveling with chronic viral hepatitis.Tropical diseases, travel medicine and vaccines · 2026Review
- Epidemiology of respiratory infections during the different levels of non-pharmaceutical interventions.BMC pediatrics · 2025Article
- Acute severe hepatitis in children following extrahepatic infection in South Korea: etiology, clinical course, and outcomes.Acute and critical care · 2025Article
- Clinical metagenomics: ethical issues.Journal of medical microbiology · 2025Article
- International outbreak of acute pediatric hepatitis: Was acetaminophen the missing link?Pediatric investigation · 2024Article
- Letter to the editor (response to Vajro and colleagues).Virulence · 2024Article
- Retrospective analysis of hospital electronic health records reveals unseen cases of acute hepatitis with unknown aetiology in adults in Oxfordshire.BMC public health · 2024Article
- COVID-19 Pandemic and its Impact on Vaccine Hesitancy: A Review.Oman medical journal · 2024Review
- The Outbreak of Unexplained Acute Hepatitis in Children: The Role of Viral Infections in View of the COVID-19 Pandemic.Viruses · 2024Article
- Acute Hepatitis of Unknown Origin in Children: Analysis of 17 Cases Admitted to the Bambino Gesù Children's Hospital in Rome.Microorganisms · 2024Article
- Global Prevalence of Preexisting Antibodies against Human Adenoviruses, Surveyed from 1962 to 2021.Intervirology · 2024Review
- Pathogenicity and virulence of human adenovirus F41: Possible links to severe hepatitis in children.Virulence · 2023Review
- A dual role for adeno-associated virus in human health.Virology journal · 2023Article
- Liver Transaminases in Pediatric Adenovirus Infection-A Five-Year Study in Two Major Reference Centers from Romania.Microorganisms · 2023Article
- Changing patterns of infectious diseases in children during the COVID-19 pandemic.Frontiers in cellular and infection microbiology · 2023Review
Corrections and comments
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Authors and funding
26 authors at 20 institutions in 14 countries.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.