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Hepatitis in children: What’s behind the outbreaks?

BMJ 2022; 377 doi: https://doi.org/10.1136/bmj.o1067 (Published 26 April 2022) Cite this as: BMJ 2022;377:o1067

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Re: Hepatitis in children: What’s behind the outbreaks?

Dear Editor

We read with keen interest the recent article in The BMJ about cases of idiopathic hepatitis in children around the world. We are concerned that the gains of multi-sectoral mitigation responses to COVID-19 is under threat by this evolving situation. Cases of idiopathic acute hepatitis were first identified in Scotland among 11 children aged one to five years between January to March 2022. The World Health Organization (WHO) was notified of these cases on April 5, 2022. [1] The outbreak in Scotland triggered retrospective investigations across the UK, leading to identification of 74 cases in children admitted to hospitals in since January 2022. [2] This coordinated case finding effort involved assessment of exposure history, toxicological testing and additional laboratory tests. By April 8, 2022, the WHO was notified of the 74 cases that fulfilled the case definition (49 cases in England, 13 in Scotland inclusive of 11 cases above, and 12 in Wales and Northern Ireland). [1]

By April 11, 2022, the usual causes of infectious hepatitis (hepatitis A to E) had been excluded from all 74 cases of hepatitis, while the coronavirus and/or adenovirus had been detected in several of the children. By April 29, 2022, the total number of cases had risen to 145: 108 in England, 17 in Scotland, 11 in Wales and 9 in Northern Ireland. A total of 10 of the 145 affected children have required liver transplantation and they will require immunosuppressive drugs for the rest of their lives, which will put them at risk of other infections. Findings suggest that these cases may be linked to adenovirus type 41 infection [2], however, several potential causes such as drugs, toxins, or environmental exposure are still under investigation. Parents are advised to watch out for symptoms of hepatitis such as high fever, jaundice, dark urine and pruritus whilst supervising good handwashing and hygiene at home.

Initially there were concerns that these new hepatitis cases could be linked to COVID-19 vaccination. However, this is unlikely to be the case as the COVID-19 vaccine is only offered to children over 5 years in the UK. [3] The UK Heath Security Agency (UKHSA) has stated that there is no link between these hepatitis cases and COVID-19 vaccination. [4] It is interesting to note the alternative causal hypothesis of a yet-to-be-identified non-native virus that is reflected in the article in The BMJ (https://www.bmj.com/content/377/bmj.o1067).

Following the notifications from the UK, cases of idiopathic hepatitis have been reported in 14 other countries including in Europe, American and Asia. This is eliciting concerns of cross-border spread. [5] It is therefore vital to leverage existing clinical and public health surveillance mechanisms that facilitated early detection and management of COVID-19 to unravel the cause of these cases of idiopathic hepatitis.

Greater priority should be given to viral hepatitis as it causes an estimated 1·34 million deaths annually, a figure comparable with deaths caused by infectious diseases such as HIV/AIDS, tuberculosis, and malaria. [6] Furthermore, the number of deaths from HIV, tuberculosis and malaria have all declined since 2008, while global deaths from chronic hepatitis show no sign of reducing. [7]

The World Health Assembly in 2016 passed a resolution to eliminate viral hepatitis as a public health problem, defined as: i) a reduction in hepatitis-related deaths by 65% and ii) new chronic hepatitis by 90%, by 2030. [8] However, achieving these targets require all countries to significantly scale-up interventions to prevent the transmission of hepatitis and improve access to testing and treatment. The current outbreak of viral hepatitis among children in 15 countries is a poignant reminder of what remains to be done to achieve these targets.

References
1. UK Health Security Agency. Increase in hepatitis (liver inflammation) cases in children under investigation. 12 April 2022. https://www.gov.uk/government/news/increase-in-hepatitis-liver-inflammat...
2. Wilson C. Mystery outbreak of hepatitis in children investigated in the UK. New Scientist. https://www.newscientist.com/article/2315740-mystery-outbreak-of-hepatit...
3. Reed J. Childhood hepatitis: Why are we seeing an unusual spike in cases? BBC News. 9 April 2022. https://www.bbc.co.uk/news/health-61025140
4. GOV.UK. Increase in hepatitis (liver inflammation) cases in children under investigation. Available at: https://www.gov.uk/government/news/increase-in-hepatitis-liver-inflammat...
5. World Health Organization (15 April 2022). Disease Outbreak News; Acute hepatitis of unknown aetiology - the United Kingdom of Great Britain and Northern Ireland. Available at: https://www.who.int/emergencies/disease-outbreak-news/item/acute-hepatit...
6. Rob Brierley R. Elimination of viral hepatitis by 2030: ambitious, but achievable. The Lancet Gastroenterology & Hepatology 2019; Volume 4, Issue 2, 88 - 89
7. Cox AL, El-Sayed MH, Kao JH, et al. Progress towards elimination goals for viral hepatitis. Nat Rev Gastroenterol Hepatol 2020; 17, 533–542 (2020). https://doi.org/10.1038/s41575-020-0332-6.
8. Smith S, Harmanci H, Hutin Y. Global progress on the elimination of viral hepatitis as a major public health threat: An analysis of WHO Member State responses. 2017. JHEP Reports 2019: 1(2): 81-89

Competing interests: No competing interests

05 May 2022
Akaninyene Asuquo Otu
Medical Doctor
Bassey Ebenso [1], John Walley [1], Josep Mercader Barceló [2] (1. Nuffield Centre for International Health and Development, Leeds Institute of Health Sciences, University of Leeds, Leeds, UK. 2. Department of Fundamental Biology and Health Sciences, University of the Balearic Islands (UIB))
Leeds Teaching Hospitals NHS Trust, Leeds, UK