Hepatitis: A mysterious increase in cases among children is associated with a virus that was thought to be harmless

Two studies have associated a mysterious increase in unexplained inferior hepatitis cases in children with adeno-associated virus 2, which infects almost everyone in childhood.

To Michael Page

Two independent studies of British children with unexplained liver damage or hepatitis found a virus called adeno-associated virus 2 in almost all children, but found it in other similar children. did not. Almost all children with hepatitis also have genetic mutations that affect the immune response.

Adeno-associated virus 2, or AAV2, is a common virus that infects almost everyone in childhood, but was previously not thought to cause illness. The virus can integrate its DNA into the genome of infected cells, so it stays in the body indefinitely.

However, AAV2 is fairly unusual in that it can only replicate in the presence of other viruses, such as: Adenovirus Or herpes virus. Therefore, it is unclear whether AAV2 is the cause of hepatitis or just an indicator of adenovirus infection. Emma Thompson At the University of Glasgow, England.

The findings suggest that either AAV2 or another virus may cause liver damage through an unknown immune mechanism in children with a genetic predisposition. ..

“There may be an immune-mediated cause of hepatitis caused by the virus, but more work is needed to test that hypothesis,” says Thomson.

Thomson suspects that a small number of these cases have been unrecognized for years. In Scotland, covid-19 restrictions may have reduced the number of adenovirus infections, and relaxed measures may have increased the peak of adenovirus infections, resulting in many cases at the same time.

“I don’t think the blockage caused this, I’m just looking at it all at once,” Thomson said.

The Scottish doctor was there in April of this year. Reported a cluster of cases Percentage of infants with liver damage that is not usually due to the hepatitis virus that causes such cases.Children say they initially had gastrointestinal symptoms such as diarrhea Antonia HoAlso at the University of Glasgow, he developed hepatitis in the next few weeks.

Worldwide, more than 1000 cases of unexplained hepatitis in children have been reported. Most have recovered, but so far 22 children have died.

Ho says the real numbers can be higher than this. Many countries do not test for hepatitis virus, so it is not possible to identify cases that are not caused by the hepatitis virus.

To identify the cause, Ho, Thomson et al. In blood samples from 9 children with hepatitis, 12 healthy children of the same age, and 13 children with adenovirus infection but no liver damage. All DNA and RNA were sequenced. AAV2 Found in all 9 children Accompanied by hepatitis, but not found anywhere else. Liver samples were available for 4 of the 9 children, and AAV2 was present in all 4 children.

The team also found that eight out of nine children have a genetic mutation called. HLA-DRB1 * 04:01 It can affect the immune response to infections. This variant is found in only 16 percent of Scottish people.

Another team led by Judith Broyer A similar study was conducted at the UCL Great Ormond Street Child Health Institute in London, comparing 28 children with hepatitis with another 136 children. The findings were similar, with AAV2 found in the blood of 27 of 28 children, not in other children, or at very low levels.

Broyer’s team also found AAV2 RNA in five liver samples, but could not find viral proteins or see viral particles under an electron microscope. “This suggests to us that there is an indirect viral mechanism,” Breuer says.

Thomson believes that the SARS-CoV-2 coronavirus is “very unlikely” to play any role in the development of these hepatitis cases. For example, affected children were less likely to have been infected with covid-19 in the past than other children.

In the UK, the number of cases of hepatitis in children is currently declining. Briar said international cooperation would be needed to carry out larger studies to confirm the findings and seek to elucidate the underlying mechanisms.

Thomson says it’s too early to talk about treatment until more is known.