The number of mysterious cases of acute hepatitis in children continues to grow, with hundreds of incidences now being reported worldwide. But the cause of the surge still hasn鈥檛 been established.
From around January, doctors in the UK noticed that young children, mostly those under 5, were suddenly developing liver inflammation, known as acute hepatitis.
As of 26 May, the World Health Organization had received 650 reports of in children under 16 across 33 countries. Of these, 222 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.
Advertisement
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 of the condition are vomiting and jaundice, a yellowing of the skin and eyes that occurs when the liver doesn鈥檛 mop up a waste product called bilirubin. Other symptoms include nausea, stomach pain, itchy skin and unusually coloured urine or faeces.
Hepatitis can be caused by poisonous substances, by viruses 鈥� usually the hepatitis A, B, C, D and E viruses 鈥� and occasionally by someone鈥檚 immune system attacking their liver.
In children, acute hepatitis is very rare. When it does occur, 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 virus behaving 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, such as paracetamol.
Another explanation is that we are finding more cases because doctors are now looking for them. 鈥淚t is not yet clear whether there has been an increase in the number of cases of hepatitis in children, or improvements in detecting cases,鈥� .
What can be ruled out is any connection with coronavirus vaccines, as 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, , the UKHSA has reported. 鈥淭he investigation continues to suggest a strong association with adenovirus,鈥� . 鈥淲hile [adenoviruses] don鈥檛 typically cause hepatitis, it is a known rare complication.鈥�
However, adenovirus-related hepatitis usually . What鈥檚 more, the most common adenovirus in the tested children, called 41F, isn鈥檛 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 amid the covid-19 restrictions. However, adenoviruses cause hepatitis by infecting liver cells directly and the virus hasn鈥檛 been found in liver tissue samples taken from some of the affected children.
The adenovirus hypothesis 鈥渄oes not quite fit鈥�, says Petter Brodin at Imperial College London.
The next suspect is SARS-CoV-2. There are reports of the coronavirus 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 (MIS-C) weeks after the initial covid-19 infection.
鈥淚 think we have seen hepatitis as part of MIS-C before, but not in the numbers that are being seen now,鈥� she says. This increase could be due to millions of children being infected by the omicron variant in recent months.
Antibody tests in countries such as Israel suggest that all affected children there have had covid-19, according to Gurdasani, but such tests haven鈥檛 been done in the UK.
Another possibility is that in some rare SARS-CoV-2 variants, 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鈥檚 guts that oversensitise their immune systems, leading to an over-the-top response to adenoviruses.
Such a 鈥渟uperantigen effect鈥� could be detected in blood samples, says Brodin, which his team plans to do.
Establishing whether these acute hepatitis cases are due to a direct infection or a post-infection immune overreaction is crucial because their treatments are very different, says Gurdasani. For example, steroids, which are used to treat children in some countries, can dampen immune overreactions, but worsen infections.
