14 | New Scientist | 11 June 2022
THE number of mysterious cases
of acute hepatitis in children
continues to grow, with hundreds
of incidences being reported
worldwide. But the cause of the
surge still hasn’t been established.
From around January, doctors
in the UK noticed that young
children, mostly those under 5,
were suddenly developing liver
inflammation, or acute hepatitis.
As of 26 May, the World Health
Organization had received 650
reports of probable, sudden-onset
hepatitis with no known cause
in children under 16 across 33
countries. Of these, 222 cases were
in the UK and 216 were in the US.
The remaining cases were largely
scattered across the rest of Europe
and North America, but incidences
have also been reported in
countries including Argentina,
Indonesia and Singapore.
Most of the children have
recovered, but 38 (6 per cent)
needed liver transplants and
nine (1 per cent) died.
According to the UK Health
Security Agency (UKHSA),
the most common symptoms
are vomiting and jaundice: a
yellowing of the skin and eyes that
occurs when the liver doesn’t mop
up the waste product bilirubin.
Hepatitis can be caused by
poisonous substances, by viruses –
usually the hepatitis A, B, C, D and
E viruses – and occasionally by
someone’s immune system
attacking their liver.
In children, acute hepatitis
is very rare. When it occurs, it
is usually due to the food-borne
virus hepatitis A, but this and
the other hepatitis viruses
have been ruled out amid
the ongoing outbreak.
Health officials are exploring
many potential explanations.
In broad terms, these are: a new
variant of a known virus or a new
virus altogether; an existing virusbehaving differently, perhaps
due to some interaction with
SARS-CoV-2; a post-infection effect
of covid-19; an environmental
factor, such as a toxin; or overuse
of liver-damaging drugs.
Another explanation is that we
are finding more cases because
doctors are looking for them. “It
is not yet clear whether there has
been an increase in the number
of cases of hepatitis in children, or
improvements in detecting cases,”
the US Centers for Disease Control
and Prevention has stated.
What can be ruled out is any
connection with coronavirus
vaccines, because most affected
children are unvaccinated.
In the UK, the main suspect is
an adenovirus, a common virus
that usually causes a cold in
children. Of the affected children
there who have been tested for
an adenovirus, 68 per cent were
positive, the UKHSA has reported.
“The investigation continues tosuggest a strong association with
adenovirus,” it has stated. “While
[adenoviruses] don’t typically
cause hepatitis, it is a known
rare complication.”
However, adenovirus-related
hepatitis usually only affects
children with compromised
immune systems. What’s more,
the most common adenovirus
in the tested children, called 41F,
isn’t known to cause hepatitis
even in immunocompromised
people, says Deepti Gurdasani at
Queen Mary University of London.It has been suggested that
adenoviruses are causing
more severe infections because
many young children were less
exposed to them because of
covid-19 social restrictions.
However, adenoviruses cause
hepatitis by infecting liver cells
directly and the virus hasn’t been
found in liver tissue samples takenfrom some of the affected children.
The adenovirus hypothesis “does
not quite fit”, says Petter Brodin
at Imperial College London.
The next suspect is SARS-CoV-2.
There are reports of it occasionally
causing hepatitis by infecting liver
cells. But most of the children
with acute hepatitis tested
negative for covid-19.
Hepatitis may be a later
consequence of covid-19.
Gurdasani points out that in
rare cases, SARS-CoV-2 triggers
multisystem inflammatory
syndrome in children (MIS-C)
weeks after covid-19.
“I think we have seen hepatitis as
part of MIS-C before, but not in the
numbers that are being seen now,”
she says. This rise could be due to
millions of children being infected
by the omicron coronavirus
variant in recent months.
Antibody tests in countries such
as Israel suggest that all the affected
children there have had covid-19,
according to Gurdasani, but such
tests haven’t been done in the UK.
Another possibility is that in
some rare SARS-CoV-2 variants,
part of one viral protein resembles
part of a human protein and
somehow triggers an immune
attack on the liver.
Brodin has proposed that
hepatitis could be triggered
by persisting pockets of SARS-
CoV-2 in children’s guts that
oversensitise their immune
systems, leading to an over-the-
top response to adenoviruses.
Establishing whether these
acute hepatitis cases are due
to a direct infection or a post-
infection immune overreaction
is crucial because treatment
would be very different,
says Gurdasani. For example,
steroids, which are prescribed to
children in some countries, can
dampen immune overreactions,
but worsen infections. ❚Michael Le PageChildren’s healthHepatitis outbreak still a mystery
Hundreds of hepatitis cases with no known cause have now been reported in children globally
Delegates at the World
Health Assembly in Geneva,
Switzerland, in MayNews
“ The investigation
continues to suggest
a strong association
with adenovirus”RE
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