British researchers unravel the possible cause of mysterious cases of hepatitis affecting young children, finding that the serious liver condition was linked to the co-infection of two common viruses, but not the coronavirus.
The World Health Organization (WHO) has reported at least 1,010 probable cases, including 46 who have needed transplants y 22 deaths by the disease since last October.
In Spain, the 40 cases of acute hepatitis of unknown origin in children according to the European Center for Disease Prevention and Control (ECDC) and the World Health Organization (WHO) Regional Office for Europe.
Previous theories had focused on a spike in commonly found adenovirus infections being behind the cases.
But in two new studies Conducted independently and simultaneously in Scotland and London, the scientists found that another virus, AAV2 (adeno-associated virus 2), played an important role and was present in 96% of all patients examined.
AAV2 is not normally known to cause disease and cannot replicate itself without the presence of another ‘helper’ virus.
Both teams concluded that coinfection with AAV2 and an adenovirus, or sometimes with the herpesvirus HHV6, offered the best explanation for the severe liver disease.
The presence of the AAV2 virus is associated with unexplained hepatitis in children
“The presence of the AAV2 virus is associated with unexplained hepatitis in children,” said Professor of Infectious Diseases Emma Thomson, from the University of Glasgow, who led the Scottish work, in a statement.
But he also cautioned that it was not yet clear whether AAV2 was causing the disease or rather a biomarker of an underlying adenovirus infection, which is more difficult to detect but is the main pathogen.
The two studies looked at both patients who got hepatitis and those who didn’t, and found that AAV2 was mostly present in those who got the disease, not those who didn’t.
The Scottish study also looked at the genes of the children who had gotten sick and those who hadn’t, focusing on differences in their Human Leukocyte Antigen that could explain why some are more susceptible than others.
Both teams ruled out recent or previous SARS-CoV-2 infection as a direct cause.
No coronavirus was found in the patients’ livers, and although the Scottish study found that two-thirds of patients had coronavirus antibodies, that rate was similar to the general population prevalence among children at the time.
It’s not clear why hepatitis cases have spiked recently, but both teams highlighted the possibility that lockdowns may have contributed, either by lowering children’s immunity or changing patterns of virus circulation.
Deirdre Kelly, a professor of pediatric hepatology at the University of Birmingham who was not involved in the work, said: “I think that is a plausible explanation for these cases. Coinfection seems to be the key.”
However, he added, further work is needed to to understand why some children develop serious illness and require a transplant.
Thomson said it was also important to “understand more about the seasonal circulation of AAV2, a virus that is not routinely monitored.”
“It may be that a peak of adenovirus infection has coincided with a peak of AAV2 exposure, leading to an unusual manifestation of hepatitis in susceptible young children.”