BQ Journal Vol 48 - Q3 2022 - 27

Early Release
Summary
What is already known about this topic?
Following identification of pediatric hepatitis cases of unknown
etiology in the United States and the United Kingdom, CDC
issued a request in April 2022 for U.S. providers to report
additional cases. Many reported cases had test results positive
for adenovirus, which is not known to cause hepatitis in
immunocompetent children.
What is added by this report?
Analyses of four data sources did not indicate recent increases
in hepatitis-associated emergency department visits or
hospitalizations, liver transplants, or adenovirus types 40/41
percent positivity among U.S. children compared with
pre-COVID-19 pandemic levels.
What are the implications for public health practice?
Current data do not suggest an increase in pediatric hepatitis or
adenovirus types 40/41 above pre-COVID-19 pandemic
baseline levels; continued surveillance is important to monitor
changes over time.
entire U.S. population, nor do they represent the same catchment
areas. Similarly, Labcorp data represent only one large
laboratory network and are not deduplicated to the patient
level. The extent to which changes in testing volume might
be due to changes in laboratory market share or test-ordering
practices could not be determined, although the percentage of
positive test results should not be substantially affected. Fifth,
although the Labcorp assay cannot distinguish between adenovirus
types 40 and 41, nearly 90% of adenovirus detections
in U.S. children with gastroenteritis are type 41 (10). Sixth,
cases of acute hepatitis of unknown etiology are generally rare;
thus, small changes in incidence might be difficult to detect
and interpret. Finally, these results are intended to provide an
overview of trends in pediatric acute hepatitis of unspecified
etiology and adenovirus types 40/41 in the United States and
cannot be used to infer or disprove a causal link between these
two illnesses.
These analyses, based on four data sources, did not indicate a
recent increase in hepatitis-associated ED visits or hospitalizations
among children aged 0-11 years, liver transplants among
children aged 0-17 years, or percentage of specimens positive
for adenovirus types 40/41 among children aged 0-9 years in
the United States compared with pre-COVID-19 pandemic
levels. The potential role of adenovirus in the etiology of the
newly reported hepatitis cases is unknown; ongoing investigations
are assessing this hypothesis along with the possible
role of other factors, including current or past infections with
SARS-CoV-2, the virus that causes COVID-19. It remains
unknown whether the recently reported cases represent a
novel etiology of pediatric acute hepatitis or a previously
6
MMWR / June 14, 2022 / Vol. 71
existing phenomenon that is now being detected. The rarity
of this outcome makes it difficult to detect small changes, and
pandemic-associated disruptions in health care-seeking behavior
and infectious disease epidemiology might still be normalizing.
Ongoing assessment of trends in addition to enhanced
epidemiologic investigations will help contextualize reported
cases of acute hepatitis of unknown etiology in U.S. children.
Corresponding author: Anita K. Kambhampati, ncirddvdgast@cdc.gov.
1Division of Viral Diseases, National Center for Immunization and Respiratory
Diseases, CDC; 2Division of Health Informatics and Surveillance, Center for
Surveillance, Epidemiology, and Laboratory Services, CDC; 3Epidemic
Intelligence Service, CDC; 4ICF, Atlanta, Georgia; 5Division of Viral Hepatitis,
National Center for HIV, Viral Hepatitis, STD, and TB Prevention, CDC;
6Booz Allen Hamilton, Atlanta, Georgia; 7Molecular Microbiology Department,
Center for Esoteric Testing, Labcorp, Burlington, North Carolina.
All authors have completed and submitted the International
Committee of Medical Journal Editors form for disclosure of potential
conflicts of interest. Suzanne E. Dale reports Labcorp contracts with
BioMerieux for BioFire equipment and reagents to perform testing,
travel funding for a conference presentation from SpeeDx, and stock
and stock options from Labcorp as part of employee compensation.
No other potential conflicts of interest were disclosed.
References
1. Baker JM, Buchfellner M, Britt W, et al. Acute hepatitis and adenovirus
infection among children-Alabama, October 2021-February 2022.
MMWR Morb Mortal Wkly Rep 2022;71:638-40. PMID:35511732
https://doi.org/10.15585/mmwr.mm7118e1
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of unknown aetiology among young children, Scotland, 1 January 2022
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https://doi.org/10.2807/1560-7917.ES.2022.27.15.2200318
3. World Health Organization. Multi-country - acute, severe hepatitis of
unknown origin in children. Geneva, Switzerland: World Health
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https://www.doi.org/10.15585/mmwr.mm7118e1 https://www.doi.org/10.2807/1560-7917.ES.2022.27.15.2200318 https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON376 https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON376 https://www.doi.org/10.1128/CMR.5.3.262 https://www.doi.org/10.1128/CMR.5.3.262 https://doi.org/10.1002/sim.5595 https://doi.org/10.1002/sim.5595 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1073704/acute-hepatitis-technical-briefing-2.pdf https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1073704/acute-hepatitis-technical-briefing-2.pdf https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1073704/acute-hepatitis-technical-briefing-2.pdf https://doi.org/10.2807/1560-7917.ES.2022.27.19.2200370 https://doi.org/10.2807/1560-7917.ES.2022.27.19.2200370 https://www.doi.org/10.2807/1560-7917.ES.2022.27.19.2200369 https://www.doi.org/10.2807/1560-7917.ES.2022.27.19.2200369

BQ Journal Vol 48 - Q3 2022

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