Investigation into mystery hepatitis outbreaks escalates

The US Centers for Disease Control and Prevention (US CDC) has become the latest health body to open an investigation into a spate of unexplained hepatitis cases in children that has left doctors confused and concerned.  
 
Reports emerged in children in the US and Europe on 5 April, but there is anecdotal evidence that cases were occurring as far back as October 2021.
 
Nine in 10 US-based children involved in the CDC study have been hospitalised as a result of the infection, while 14% of the 109 cases under investigation have required a liver transplant and five have died.
 
Investigations are also being conducted in Jakarta, where three children died last month with symptoms similar to those now being reported in five of the six World Health Organization (WHO) regions.
 
Dr Jay Butler, the CDC’s deputy director of infectious diseases, described the situation as ‘evolving’ and said some common causes of viral hepatitis have been considered but were not found in any of the cases.
 
However, Dr Philippa Easterbrook, a senior scientist in the WHO’s global hepatitis program, did recently suggest that there may be a potential link to a particular type of adenovirus, called F41, which was found in 72 out of 84 cases that had been tested.
 
While much of the testing has been restricted to the UK, adenovirus has reportedly been detected in more than 50% of the US CDC cases.
 
Dr Easterbrook also noted that many other viruses commonly linked with the infection, such as hepatitis A–E viruses, cytomegalovirus and glandular fever, have not been identified.
 
No mystery hepatitis cases have been identified in Australia yet, and there is no definitive evidence to suggest the rare condition itself is spreading around the world. However, the Kirby Institute’s Professor Andrew Lloyd said the fact that it occurred initially in England and then in Europe ‘suggests that it can spread between countries’.
 
Professor Peter White, also from the University of New South Wales, says should it be confirmed that a virus outside of those commonly associated with the infection is causing hepatitis, such as adenovirus F41, it would be ‘something new that we haven’t seen for 30 years’.
 
‘There are about 113 different types of adenovirus, but F41 and a few of the others are well known to cause gastro,’ he said.
 
‘The liver is really like the helper of the gastrointestinal system, so if the virus is now capable of infecting the liver, that would not be a surprise to me or any other virologist.
 
‘If this virus now infects liver cells, that would indicate a tropism change and I would say this suggests something must have changed with the virus.’
 
For doctors treating children in the US who have formed part of the CDC’s investigation, the severity of the illness has been notable.
 
‘Even during the first case, I thought it was weird,’ Dr Markus Buchfellner, a paediatric infectious disease specialist at the University of Alabama said.
 
‘And then when the second one came in, that’s when I said, “OK, we need to talk to someone about this”.’
 
Cases have been reported in children aged from one month to 16 years old and any link to COVID vaccination has been ruled out, as the majority of infected children had not received a vaccine.
 
But University of Sydney infectious diseases paediatrician and vaccine expert Professor Robert Booy has questioned whether there could be a link to the disease itself.
 
‘The new hepatitis outbreak in children requires careful and urgent attention,’ he said.
 
‘Might this be a manifestation of co-infection with both adenovirus and COVID-19 in young children with an underlying rare genetic problem?
 
‘Adenovirus is also well known for being a commensal as well as a pathogen in children’s gastrointestinal disease. So [another] key question is was the virus actually found in inflamed liver cells?’
 
The UK Health Security Agency has also identified a potential link with dogs, finding ‘relatively high numbers of dog-owning families or other dog exposures’.
 
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COVID-19 Hepatitis infectious disease paediatric