Three studies on the outbreak of hepatitis of unknown etiology in children have been published in Nature with an accompanying editorial.

in pandemic •  2 years ago 

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We are starting to get some clarity on what may have caused the outbreak.

These studies all show an association between Adeno-Associated Virus 2 and the hepatitis outbreak. Samples were also generally high in adenoviruses. These AAVs are replication deficit and need helper viruses like adenovirus to replicate. AAVs aren't known to cause disease in humans, but they are known to have immune-mediated effects and they have a tropism for liver cells.

One study also suggested a genetic susceptibility as most of the cases had a specific mutation in a class II HLA gene.

Further study is needed to elucidate if the AAV is causing direct harm to the liver, or rather causing immune responses that are harmful to the liver, and whether other viral infections may be contributory.

These studies used control groups of similar children with hepatitis of defined etiology and others without hepatitis. Controls were low both in AAV2 as well as adenoviruses and other helper viruses suggesting that these co-infections were associated with the hepatitis.

It is unclear why these viruses that previously were considered to be mostly harmless caused these hepatitis cases. In rare cases adenoviruses have been able to cause acute hepatitis, but generally not in immunocompetent individuals. AAVs were generally considered to not cause disease, but a gene therapy trial indicated that high doses of AAVs can cause liver damage. Pandemic mitigation may have reduced circulation of these two viruses, and thus as mitigation was lifted they co-circulated amongst a susceptible population.

Some commentators suspected a role for coronavirus infection, though affected children generally had coronavirus antibodies similar to the general population and these hepatitis cases generally followed the rise in adenovirus not the coronavirus.

https://www.nature.com/articles/s41586-023-05949-1

https://www.nature.com/articles/d41586-023-00570-8

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