UKHSA: Acute Hepatitis of Unknown Etiology Update & Technical Briefing #2

#16,735

In yesterday's CDC Telebriefing On Acute Hepatitis Of Unknown Cause  we learned that the number of U.S. cases under investigation has grown to at least 109 - spanning 24 States and Puerto Rico - with 90% requiring hospitalization, 14% receiving liver transplants, and 5 dying. 

The 41-minute audio of the telebriefing can be heard here.  The transcript, as of this writing, has not been posted. 

Meanwhile the UK has posted a new update, adding 18 more cases (ttl=163), and has published their second technical Briefing. 

While an adenovirus connection is being vigorously explored by both the U.S. and UK health authorities, it is far from certain what is behind this outbreak.  Even if a adenovirus is ultimately  implicated, it may not be the sole cause.  

But since the vast majority of these cases are under the age of 5 - and are ineligible for COVID vaccination - that much maligned scapegoat on social media can be safely eliminated. 

Increase in hepatitis (liver inflammation) cases in children under investigation

Regular UKHSA updates on the ongoing investigation into higher than usual rates of liver inflammation (hepatitis) in children across the UK.

From:UK Health Security Agency updated 6  May 2022 — See all updates

Latest

The UK Heath Security Agency (UKHSA) has published its second detailed technical briefing on the UK-wide investigations into a rise in cases of sudden onset hepatitis in children, updating data and findings on cases resident in the UK up to 3 May 2022.

Since the last update on 29 April, active case finding investigations have identified a further 18 confirmed cases, bringing the total number of UK cases to 163 as of 3 May. Of these children, 11 have received a liver transplant. None have died.

Jaundice and vomiting are the most common symptoms experienced by the children affected.

The investigation continues to suggest an association with adenovirus. Adenovirus is the most frequently detected virus in samples tested.

However, as it is not common to see hepatitis following adenovirus infection in previously well children, investigations are continuing into other factors which may be contributing. These include previous SARS-CoV-2 or another infection, a change in susceptibility possibly due to reduced exposure during the pandemic, or a change in the adenovirus genome itself.

These possibilities are being tested rapidly. The association with adenovirus is undergoing a formal epidemiological study.

Research studies of the immune system are being undertaken to determine if changes in susceptibility or the effect of prior infections could be contributing factors.

There is no evidence of any link to the coronavirus (COVID-19) vaccine. The majority of cases are under 5 years old, and are too young to have received the vaccine.

Normal hygiene measures, including thorough handwashing and making sure children wash their hands properly, help to reduce the spread of many common infections, including adenovirus.

Dr Meera Chand, Director of Clinical and Emerging Infections at UKHSA, said:

It’s important that parents know the likelihood of their child developing hepatitis is extremely low. However, we continue to remind everyone to be alert to the signs of hepatitis – particularly jaundice, look for a yellow tinge in the whites of the eyes – and contact your doctor if you are concerned.

Our investigations continue to suggest that there is an association with adenovirus and our studies are now testing this association rigorously.

We are also investigating other contributors, including prior SARS-CoV-2, and are working closely with the NHS and academic partners to understand the mechanism of liver injury in affected children.

The 49-page Technical Briefing is well worth downloading and reading in its entirety.  I've posted the UK's working hypothesis below. I'll return with a brief postscript after the break. 

Part 1. Working hypotheses 

The following hypotheses are all being actively tested by the investigations in process. There are increased paediatric acute non-A-E hepatitis presentations due to: 

1. A normal adenovirus infection, due to one of: 

a. Abnormal susceptibility or host response which allows adenovirus infection to progress more frequently to hepatitis (whether direct or immunopathological), for example from lack of exposure during the coronavirus (COVID-19) pandemic. 

b. An exceptionally large wave of normal adenovirus infections, causing a very rare or under-recognised complication to present more frequently.

c. Abnormal susceptibility or host response to adenovirus due to priming by a prior infection with SARS-CoV-2 (including Omicron restricted) or another infection. 

d. Abnormal susceptibility or host response to adenovirus due to a coinfection with SARS-CoV-2 or another infection. 

e. Abnormal susceptibility or host response to adenovirus due to a toxin, drug or environmental exposure. 

2. A novel variant adenovirus, with or without a contribution from a cofactor as listed above. 

3. A post-infectious SARS-CoV-2 syndrome (including an Omicron restricted effect). 

4. A drug, toxin or environmental exposure. 

5. A novel pathogen either acting alone or as a coinfection. 

6. A new variant of SARS-CoV-2.

Even though 9 cases had been detected in Alabama (starting last fall), and were apparently under joint investigation by the state and the CDC, we didn't learn of this syndrome until a month ago when the UKHSA announced they were Investigating An Unusual Increase In Hepatitis In Children. 

Just over a week later (April 14th), in Eurosurveillance: Investigation into Cases of Hepatitis of Unknown Aetiology Among Young Children, Scotland, we learned from the Scottish Health Authority that the CDC was investigating similar cases here in the United States.

PHS is also aware of a cluster of hepatitis and adenovirus cases among children being investigated by the US Centers for Disease Control and Prevention (personal communication: Hannah L. Kirking, 12 March 2022).

Two days later we saw an announcement from the Alabama DOH on their Investigation Into 9 Young Children with Hepatitis/Adenovirus, which said the CDC was working on a HAN advisory. 

The following day the WHO published Acute hepatitis of unknown aetiology – the United Kingdom of Great Britain and Northern Ireland, and we saw reports from More Countries (Israel, Denmark, Netherlands, etc.) in the days that followed. 

Fifteen days after the UK announcement (and 5+ weeks after informing PHS) the CDC finally published a HAN advisory, where they described 9 cases (all from Alabama) and called on clinicians to report suspected cases.  

Since that announcement just over 2 weeks ago, 100 more cases (including 5 deaths) have been reported.  And that may just be the tip of the pyramid. 

While I'm sure the CDC has their hands full with the pandemic, avian flu, and a hundred other concerns, this delayed response - and the awkward initial disclosure of U.S. cases through a 3rd party - is far from the CDC's finest hour.

Hopefully, this will serve as a wake up call.  Because more threats are coming.