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Hepatitis in children: What’s behind the outbreaks?

BMJ 2022; 377 doi: (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,

The current article by Elisabeth Mahase discussing the sudden rise of severe non A-E hepatitis cases is quite informative.

In the light of current knowledge, I would like to highlight a few points.

The current approach to investigating these cases could be biased as we are only investigating the cases severe enough to get hospitalised. These cases are just the tip of the iceberg; there is an urgent need to uncover the prevalence of such viruses in children having a mild elevation of transaminases in the same vicinity.

Active search for the cofactor: From the recent report released by the UK Health Security Agency, i'ts quite evident that there is a co-factor in play since the suggested agent Adenovirus is not usually known to cause severe hepatitis in previously healthy children (1). However, given an immune-compromised state in a child recovering from COVID or some other novel virus, such a disease form might manifest. Such severe hepatitis cases have already been reported in HIV-affected and bone marrow transplant recipients (2). With the continuing current phase of the pandemic and given the tested COVID positivity was higher (16%) among the affected, versus the weekly positivity rate among the community (5-8%). However, we know that SARS-CoV-2 alone is unlikely to cause such severe liver disease since most cases wherever reported in children have been of mild elevation of transaminases (3).

A close look at the data also reveals that some other viruses like EBV, CMV and Human herpes viruses have been found in such cases, although in fewer numbers. Interestingly in some of such cases the main suspect Adenovirus is missing. In a recent study from India among children affected with severe hepatitis, positivity was found for other viruses like VZV and EBV in a similar fashion (4).

This leads us to a theory of primary insult followed by a secondary invasion of the liver, which in the case of the UK incidences is most likely to be Adenovirus. We should not forget that owing to a high number of many such viruses which are known to cause hepatitis in a host having a weakened immune system, which vary in their prevalence across the Globe, such active searches for these agents must be driven according to the affected area and not limited to testing for Adenoviruses alone.

1) Acute hepatitis: technical briefing [Internet]. GOV.UK. [cited 2022 May 3]. Available from:
2) Donald R. Carrigan P. Adenovirus Infections in Immunocompromised Patients. Am J Med. 1997 Mar 17;102(3):71–4.
3) Zhou YH, Zheng KI, Targher G, Byrne CD, Zheng MH. Abnormal liver enzymes in children and infants with COVID-19: A narrative review of case-series studies. Pediatr Obes. 2020;15(12):e12723
4) Rawat SK, Asati AA, Jain A, Mishra N, Ratho RK. COVID-19 Associated Hepatitis in Children (CAH-C) during the second wave of SARS-CoV-2 infections in Central India: Is it a complication or transient phenomenon [Internet]. medRxiv; 2021 [cited 2022 May 3]. p. 2021.07.23.21260716. Available from:

Competing interests: No competing interests

03 May 2022
Associate Professor, Dept of Microbiology, Bundelkhand Medical College, Sagar, MP , India
Dept of MIcrobiology, Bundelkhand Medical College. E mail: