In both publications, an unusual virus called adeno-associated virus-2 (AAV2) is implicated as one aspect of a complex mechanism that can cause rare and serious liver problems, including a dozen cases this year in Canadian children. The preprinted studies are from research groups at London and Glasgow, and has not yet been formally published or peer-reviewed. The teams looked at small numbers of children suffering from liver inflammation not caused by the obvious culprits, such as the common family of hepatitis viruses, alongside healthy control subjects. Researchers in both regions found high levels of AAV2 in blood samples taken from young patients with unexplained hepatitis and evidence of other viral infections. The findings suggest that co-infection with two viruses — AAV2, plus an adenovirus or, in some cases, a herpes virus — could cause hepatitis in some children. The Scottish team also noted that the majority of affected children had a particular gene, DRB1-0401. “Eight out of nine children had this particular gene … whereas in Scotland, it’s only present in 15.6 per cent,” said one of the authors of the Glasgow study, Antonia Ho, a clinical lecturer at the MRC-University of Glasgow Center for Virus Research. “So we’re wondering if, perhaps, it’s co-infection with AAV2 and an adenovirus, in children who have this particular gene, that 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 acknowledged, as more global research is needed to investigate exactly what triggered more than 1,000 possible 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 this year, including a surge that first caught the attention of British officials, then subsided and included 22 deaths. No children have died in Canada this year 24 cases of acute severe hepatitis were reported across the countryalthough two children required liver transplants. There has been intense debate about what could be at play, with scientists around the world pointing 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, neither theory has been a slam dunk. Clinicians have also raised questions about whether this is a new phenomenon, 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 set the record high. global health officials level alarm. While there are still more questions than answers, the latest British research explores some interesting possibilities, offering more possible pieces to this puzzle. Particularly intriguing — and unexpected — was the potential connection to AAV2, several scientists told CBC News. It’s what’s known as a parvovirus, which usually doesn’t replicate on its own inside the human body. WATCHES | The cause of the rare liver disease epidemic is a mystery to experts:
The cause of the rare outbreak of liver disease in children is a mystery to experts
Doctors aren’t sure what’s causing a mysterious outbreak of liver disease that has been seen in children from a dozen countries around the world. While at least one child has died, experts insist most children will make a full recovery from the disease. “It’s essentially a parasite. There has to be another DNA virus to replicate its genome,” said Charlotte Houldcroft, a virologist in the department of genetics at the University of Cambridge, who was not involved in any of the new studies. A high percentage of the population is likely to be infected with AAV2 but may never realize it. Typically, the virus is not considered to cause disease on its own, as it requires a “helper virus” to be present as well, Houldcroft said. However, some studies suggest AAV2 infectionor his use as a carrier in gene therapy to treat certain diseases, it may be associated with liver-related health problems. Houldcroft noted that the particular gene identified in patients from the Scottish group may prove to be another key factor, as it has already been linked to certain autoimmune conditions. “Genetic susceptibility would explain why this is rare,” he said. “And then the fact that maybe you need two different infections, and we had this big wave of adenovirus 41, in the UK from December 2021 to the spring of 2022 — that might explain why these rare cases clustered over time. and why did we suddenly notice this disease.”
More research, larger studies are needed
Dr. Jordan Feld, a clinician-scientist at Western Toronto Hospital’s Liver Clinic, agreed that the work presents interesting points, connecting data that may, in time, explain the rare but troubling cases emerging this year, and perhaps even some unexplained ones. childhood hepatitis cases that arose. But it’s important to validate the results beyond these two, small studies, he stressed, given all the possible factors. “When people first suggested adenovirus and first suggested 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 — largely showed that they probably were That’s not the whole story,” Feld said. There are also significant limitations to the work, both outside experts and the authors themselves noted, 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 British paper stressed that their data alone are not sufficient to rule out the impact of the Omicron variant, “the appearance of which preceded the outbreak of unexplained hepatitis,” with more results from large, case-controlled studies . Feld stressed that whatever causes unexplained hepatitis in children remains an incredibly rare phenomenon, although more medical professionals are watching closely for cases. Parents can look for tell-tale symptoms such as jaundice – yellowing of the child’s eyes and skin – dark urine, pale stools, abdominal pain and vomiting. “There is certainly not a rampant epidemic of severe acute hepatitis,” Feld said. “Well I would say, the first thing is to take a deep breath. Most kids will be completely fine.”
