Evidence map›Paper›PMID 39653515›Full record

ReviewBMJ paediatrics open2024

Acute hepatitis of unknown aetiology in children: evidence for and against causal relationships with SARS-CoV-2, HAdv and AAV2.

Deepti Gurdasani, Mallory Trent, Hisham Ziauddeen, Emmanuel Mnatzaganian, Stuart Turville, Xin Chen, Mohana Priya Kunasekaran, Abrar Ahmad Chughtai, Aye Moa, Julie McEniery and 2 more

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in BMJ paediatrics open, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Deepti Gurdasani *William Harvey Research Institute, Queen Mary University, London, UK.ORCID 0000-0001-9996-6929
Mallory Trent *Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
Hisham ZiauddeenDepartment of Psychiatry, University of Cambridge, Cambridge, UK.
Emmanuel MnatzaganianUniversity of New South Wales, Sydney, New South Wales, Australia.
Stuart TurvilleKirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
Xin ChenKirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
Mohana Priya KunasekaranKirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
Abrar Ahmad ChughtaiSchool of Population Health, University of New South Wales, Sydney, New South Wales, Australia.
Aye MoaKirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
Julie McEnieryFaculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.
Trisha GreenhalghNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.ORCID 0000-0003-2369-8088
Chandini Raina MacIntyreKirby Institute, University of New South Wales, Sydney, New South Wales, Australia rainam@protonmail.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe cause of acute paediatric hepatitis of unknown aetiology (2022) has not been established despite extensive investigation.

objectiveTo summarise the evidence for and against a causal role for human adenovirus (HAdv), adeno-associated virus 2 (AAV-2) and SARS-CoV-2 in outbreaks of paediatric hepatitis in 2022.

methodsWe appraised and summarised relevant evidence for each of the Bradford Hill criteria for causality using quantitative (statistical modelling) and qualitative (narrative coherence) approaches. Each team member scored the evidence base for each criterion separately for HAdv, AAV-2 and SARS-CoV-2; differences were resolved by discussion. We additionally examined criteria of strength and temporality by examining the lagged association between SARS-CoV-2 positivity, respiratory HAdv positivity, positive faecal HAdv specimens and excess A&E attendances in 1-4 years for liver conditions in England.

resultsAssessing criteria using the published literature and our modelling: for HAdv three Bradford Hill criteria (strength, consistency and temporality) were partially met; and five criteria (consistency, coherence, experimental manipulation, analogy and temporality) were minimally met. For AAV-2, the strength of association criterion was fully met, five criteria (consistency, temporality, specificity, biological gradient and plausibility) were partially met and three (coherence, analogy and experimental manipulation) were minimally met. For SARS-CoV-2, five criteria (strength of association, plausibility, temporality, coherence and analogy) were fully met; one (consistency) was partially met and three (specificity, biological gradient and experimental manipulation) were minimally met.

conclusionBased on the Bradford Hill criteria and modelling, HAdv alone is unlikely to be the cause of the recent increase in hepatitis in children. The causal link between SARS-CoV-2, and to a lesser degree AAV-2, appears substantially stronger but remains unproven. Hepatitis is a known complication of multisystem inflammatory syndrome in children following COVID-19, and SARS-CoV-2 has been linked to increased susceptibility to infection post-COVID-19, which may suggest complex causal pathways including a possible interaction with AAV-2 infection/reactivation in hosts that are genetically susceptible or sensitised to infection.

Indexed as

HepatitisAcute DiseaseAdenoviruses, HumanCausalityChild, PreschoolCOVID-19DependovirusHumansInfantPandemicsSARS-CoV-2COVID-19EpidemiologyhepatitispaediatricStatistics

Identifiers

PMID39653515
PMCPMC11628968

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.