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Review
. 2022 May 24;10(6):973.
doi: 10.3390/healthcare10060973.

Hepatitis of Unknown Origin and Etiology (Acute Non HepA-E Hepatitis) among Children in 2021/2022: Review of the Current Findings

Malik Sallam  1   2   3 , Azmi Mahafzah  1   2 , Gülşen Özkaya Şahin  3   4 , On Behalf Of Escmid Study Group For Viral Hepatitis-Esgvh
Affiliations
Review

Hepatitis of Unknown Origin and Etiology (Acute Non HepA-E Hepatitis) among Children in 2021/2022: Review of the Current Findings

Malik Sallam et al. Healthcare (Basel). .

Abstract

Several clusters and individual cases of acute hepatitis have been reported in the US, Europe and recently in Asia and Central America since October 2021. A laboratory investigation of the common viral hepatitis agents (HAV, HBV, HCV, HDV and HEV) yielded negative results prompting the use of the term "acute non HepA-E hepatitis" to describe this condition. The cases were characterized by the manifestations of acute hepatitis (abdominal pain, vomiting, diarrhea, jaundice and very high levels of liver enzymes) affecting children with a median age of 3-4 years. The exact underlying etiology has not been revealed yet; however, a leading hypothesis is that an infectious agent is the culprit, underlying cause or a risk factor for acute non HepA-E hepatitis occurrence. So far, laboratory testing has shown the presence of the group F human adenovirus serotype 41 (HAdV-F41) in about three-fourths of the investigated cases. As of 13 May 2022, more than 450 cases were reported worldwide, the majority of which were in the UK (n = 176), the US (n = 109), 13 European countries (at least 103 cases) and in Argentina, Brazil, Canada, Costa Rica, Indonesia, Israel, Japan, Palestine, Panama, Singapore and South Korea. Vigilant surveillance and epidemiologic investigations to identify further cases are warranted to delineate the features of this emergent public health issue. The possible role of environmental and toxic agents including foodborne toxins should also be considered. Specific guidelines for identification of further cases are necessary, particularly in low-income settings where testing for adenoviruses is not considered routinely. A genetic analysis of HAdV-F41 isolates is recommended to assess the potential changes in the virus genome with subsequent possible altered virus behavior. Immunopathogenesis is another possibility that should be evaluated considering the lack of viral structures in liver biopsies of the affected children in the US.

Keywords: novel; outbreak; public health promotion; unknown etiology; unknown hepatitis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The global geographic distribution of acute non HepA-E hepatitis as of 13 May 2022. The map was generated in Microsoft Excel, powered by Bing, © GeoNames, Microsoft, Navinfo, TomTom, Wikipedia. We are neutral with regard to jurisdictional claims in this map.
Figure 2
Figure 2
The distribution of acute non HepA-E hepatitis in the United States as of 13 May 2022. The map was generated in Microsoft Excel, powered by Bing, © GeoNames, Microsoft, Navinfo, TomTom, Wikipedia.
Figure 3
Figure 3
The geographic distribution of acute non HepA-E hepatitis in Europe as of 13 May 2022. The map was generated in Microsoft Excel, powered by Bing, © GeoNames, Microsoft, Navinfo, TomTom, Wikipedia. We are neutral with regard to jurisdictional claims in this map.
See this image and copyright information in PMC

References

    1. Christie B. Scientists Search for Cause of Hepatitis Cases in Children. BMJ. 2022;377:o982. doi: 10.1136/bmj.o982. - DOI - PubMed
    1. World Health Organization (WHO) Acute Hepatitis of Unknown Aetiology—The United Kingdom of Great Britain and Northern Ireland. [(accessed on 29 April 2022)]. Available online: https://www.who.int/emergencies/disease-outbreak-news/item/acute-hepatit....
    1. Centers for Disease Control and Prevention (CDC) Recommendations for Adenovirus Testing and Reporting of Children with Acute Hepatitis of Unknown Etiology—Distributed via the CDC Health Alert Network. [(accessed on 28 April 2022)]; Available online: https://emergency.cdc.gov/han/2022/han00462.asp.
    1. European Centre for Disease Prevention and Control Increase in Severe Acute Hepatitis Cases of Unknown Aetiology in Children—28 April 2022. [(accessed on 28 April 2022)]. Available online: https://www.ecdc.europa.eu/en/publications-data/increase-severe-acute-he....
    1. Marsh K., Tayler R., Pollock L., Roy K., Lakha F., Ho A., Henderson D., Divala T., Currie S., Yirrell D., et al. Investigation into Cases of Hepatitis of Unknown Aetiology among Young Children, Scotland, 1 January 2022 to 12 April 2022. Eurosurveillance. 2022;27:2200318. doi: 10.2807/1560-7917.ES.2022.27.15.2200318. - DOI - PMC - PubMed