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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

In normal times, I would have expected a rapid output of relevant clinical data and early research into the medical domain. This hasn't happened with the hepatitis outbreak, despite 114 of 169 total reported cases having occurred in UK. We surmise on thin and disparate evidence. My supremely unqualified view is based on information which I found on Twitter (!) (thanks to @farid_jalali ).

My guess is that it's a new specific presentation of MISC-C from infection with the BA.2 lineage now running riot in UK. I don't think Adenovirus-related acute co-infection, or even potentiation, is as likely.

The frequency of Covid in these patients may well be higher than is apparent from the 16% 'Covid not detected' cohort. SARS-Cov-2 test positivity was much higher anyway in patients with hepatitis (16%) than the background rate of 5-8%, but this was only from testing on admission - so Covid infections in the preceding six weeks may not have been detected, and a delay in onset of MISC-C is usual. Covid is very prevalent and MISC-C only occurs in children. In the UK study, there was similar blood positivity for Covid (n=10) as for Adenovirus (n=11).

Of 100 described cases of severe adenoviral hepatitis, all were severely immunocompromised and all liver biopsy samples had hepatocyte adenovirus inclusions on histopathology - none of which were serotype Ad 41. In the current Alabama study, none of the samples had any adenovirus inclusions or positivity within hepatocytes.

Serotype Ad 41 has never been known to cause hepatitis. Adenoviruses commonly inhabit tonsils/adenoids on a chronic ongoing basis and viraemia can then occur when the host is immunocompromised eg during an attack of hepatitis. 'Acute' infection can still produce live virus 3 months to >1 year later and replication can persist for years in healthy people. So Adenovirus 41 may be less co-factor and more freeloader.

Whether the hepatitis is a primary viral or secondary immune insult is an important starter question with regard to treatment approach. I'd have expected to have had at least some better information now, since both mechanisms are already known in viral hepatitis. Aside from the limited UKHSA/CDC publications, is it a reasonable question to ask if there might be a political angle to the seeming dearth of information in such an alarming situation? Are they just hoping it will go away without having had to explain it as a Covid-related harm in children?

Competing interests: No competing interests

03 May 2022
Nick Mann