As scientists around the world race to figure out what has caused a wave of previously unexplained cases of hepatitis in children – including some who have needed liver transplants – two new UK studies offer new clues.
Both papers implicated an unusual virus called adeno-associated virus-2 (AAV2) as one aspect of a complex mechanism that can cause rare and serious liver problems, including two dozen cases this year among Canadian children.
Preprint studies are from research teams at London and Glasgow, and has not yet been officially published or peer-reviewed. The teams looked at a small number of children who suffered from liver inflammation that wasn’t caused by the obvious culprits, such as the usual family of hepatitis viruses, alongside healthy control subjects.
Researchers in both regions identified high levels of AAV2 in blood samples taken from young patients with unexplained hepatitis and signs of other viral infections.
The findings suggest that coinfection with two viruses at once — AAV2, plus adenovirus or, in some cases, herpes virus — can trigger hepatitis in certain children. The Scottish team also noted that the majority of affected children shared a specific gene, DRB1-0401.
“Eight of the nine children had this particular gene … whereas in the Scottish background it was present in only 15.6 per cent,” said one of the Glasgow study’s authors, Antonia Ho, clinical senior lecturer at the MRC-University of Glasgow Center for Research of viruses.
“So we wonder if maybe co-infection with AAV2 and adenovirus in children who have this particular gene makes them more susceptible to getting these viruses and having an abnormal immune response to them.”
Three possible factors
It’s a complex theory linking a trio of possible factors.
The early findings also do not confirm a root cause, Ho’s team acknowledges, and more global research is needed to understand exactly what caused more than 1,000 likely cases of acute severe hepatitis of unknown origin in young children in 35 countries. according to the latest data from the World Health Organization.
The total number of cases has risen sharply this year, including a surge that first caught the attention of officials in the UK, before falling to include 22 deaths. No child has died in Canada this year since 24 cases of acute severe hepatitis were registered throughout the countryalthough two children required liver transplants.
There was an intense debate about what could be played with scientists from all over the world they point the finger at viruses ranging from a common adenovirus known to cause stomach upset to the widely circulating SARS-CoV-2, the virus behind COVID-19.
So far, no theory has been nailed down. Clinicians have also raised questions about whether this is a new phenomenon at all, as medical teams have long seen sporadic cases of serious liver problems in children with no apparent cause – even before this year’s rash of cases put global health officials on high alert.
Although there are still more questions than answers, the latest UK research explores some intriguing possibilities, offering more potential pieces of this puzzle.
Particularly fascinating — and unexpected — was the possible connection to AAV2, several scientists told CBC News. This is what is known as a dependonparvovirus, which normally does not replicate itself in the human body.
WATCH | The cause of the occurrence of a rare liver disease is a mystery to experts:
The cause of a rare liver disease in children is a mystery to experts
Doctors aren’t sure what’s causing a mysterious outbreak of liver disease in children in a dozen countries around the world. Although at least one child has died, experts insist that most children will make a full recovery from the disease.
“It’s actually a parasite. It has to have another DNA virus to replicate its genome,” said Charlotte Holdcroft, a virologist in the Department of Genetics at the University of Cambridge, who was not involved in any of the new studies.
A large percentage of the population is likely infected with AAV2 but may never realize it.
The virus is generally thought not to cause disease by itself because it requires the presence of a “helper virus,” Holdcroft said. However, some studies suggest AAV2 infectionor his use as a vector in gene therapy to treat certain diseases, it may be related to health problems related to the liver.
Holdcroft noted that the specific gene identified in patients by the Scottish team could prove to be another key factor because it is already associated with certain autoimmune conditions.
“Genetic susceptibility would explain why this is rare,” she said.
“And then the fact that maybe you need two different infections and we have this big surge of adenovirus 41 in the UK from December 2021 to spring 2022 – that could explain why these rare cases have come together over time, and why we suddenly noticed this disease.”
More research, larger studies are needed
Dr. Jordan Feld, a clinician-scientist at Toronto’s Western Hospital Liver Clinic, agreed that the papers present interesting points, tying together data that in time may explain the rare but troubling cases emerging this year, and may would even some unexplained childhood hepatitis cases that were before.
But it’s important to validate the results beyond these two, small studies, he stressed, taking into account all potential factors.
“When people first proposed adenovirus and first proposed SARS-CoV-2 as the cause of it, everybody around the world went back to their samples and looked closely to see and – I would say – pretty much showed that they probably not is not the whole story,” Feld said.
There are also major limitations in the papers noted by both external experts and the authors themselves, including small sample sizes and unclear cause and effect.
The role of COVID-19 also remains unclear.
Ho, from the Glasgow team, said her team found no clear links to SARS-CoV-2 and said more cases of childhood hepatitis should have been seen during earlier waves of the pandemic if this virus was the cause .
Meanwhile, the authors of the UK paper stressed that their data alone were not sufficient to rule out the influence of the Omicron variant “whose appearance precedes the outbreak of unexplained hepatitis”, and more results from large, case-controlled studies are needed .
Feld emphasized that whatever causes unexplained hepatitis in children remains incredibly rare, although more and more medical professionals are watching closely for cases.
Parents can look for telltale symptoms, including jaundice – yellowing of the child’s eyes and skin – dark urine, pale stools, abdominal pain and vomiting.
“There is certainly no spreading epidemic of severe acute hepatitis,” Feld said. “So I would say the first thing is to take a deep breath. Most children will be perfectly fine.”
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