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Unexplained hepatitis in children is not necessarily an infectious disease
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Major progress: Unexplained hepatitis in children is not necessarily an infectious disease.
Globally, there are multiple acute hepatitis of unknown etiology in children with unknown etiology, rapid development, and even life-threatening, and the outbreak lasted for more than 3 months. The scientific community may finally find the key to the puzzle.
This may be the result of multiple factors, two independent studies from Scotland and London, UK, suggest.
On the one hand, a child may be infected with two different viruses at the same time. On the other hand, the patient’s own genetic mutation may cause the immune system to “overreact” and induce severe hepatitis.
At the same time, relevant studies have ruled out the claim that unexplained hepatitis is related to the new coronavirus.
So this disease is likely to be an autoimmune disease in nature, not an acute infectious disease.
Or due to the synergy of the two viruses
There are many causative hypotheses about acute hepatitis of unknown etiology in children.
The earliest proposed and most popular is the theory of human adenovirus (hADV) infection, especially adenovirus type 41. The New England Journal of Medicine (NEJM) published two case studies on July 13, saying that the virus was detected in about 90% of the children surveyed.
In this regard, two recent studies in the United Kingdom propose a new angle of interpretation.
They found both the effect of adenovirus infection and other factors: high levels of adeno-associated virus type 2 (AAV2) were detected in the blood and liver tissue of 96 percent of the children interviewed . The control group was almost undetectable.
“Science” magazine analyzed that almost everyone will be infected with AAV2 around the age of 10. After that, the virus lies dormant in the cell until a distant relative, such as adenovirus or herpes virus, emerges and activates it. This means that for AAV2 to make chaos in the human body, it needs other viruses to “assist” and infect the human body at the same time.
The University of Glasgow in the United Kingdom found a “possible accomplice”: 86% of the children had adenovirus (HAdV C/F) detected in the blood or liver tissue , and some children had herpes virus (HHV6B) detected .
Neither AAV2 nor adenovirus or herpes virus is a new virus. The University of Glasgow team pointed out that if its hypothesis is correct, there must be a “special background” for a large number of children with unexplained hepatitis in many countries and regions at the same time.
“The current situation emerged after the relaxation of the COVID-19 epidemic prevention measures. In the past two years, the transmission of the virus that was interrupted by wearing masks and social distancing has become active again. In addition, in the past two years, children have been overprotected and rarely There is an opportunity to be exposed to other pathogens, so pre-existing immunity will also decline. This will lead to more infections in children, or promote an increase in childhood hepatitis cases.” The American life science website STAT quoted the research team’s analysis as saying.
Emma Thomson, a co-author of the study and an infectious disease specialist at the University of Glasgow’s Centre for Virology Research, pointed out that this explains why acute hepatitis of unknown origin occurs in a short period of time, and there is no difference between children in different countries and regions. intersection. “Easing COVID-19 restrictions means that children may be exposed to many viruses at once, rather than gradually being exposed to more viruses.”
Discover special genotypes
Previously, the aforementioned “adenovirus infection pathogenic theory” has encountered many challenges.
Opponents argue that human adenoviruses are less destructive. It mainly invades the respiratory tract and causes liver damage and liver failure in rare cases, mostly in immunocompromised children.
The multi-country epidemiological survey from March to the present showed that more unexplained hepatitis cases occurred in previously healthy infants and young children.
“Is it possible that liver damage may be a sequela of viral infection? Adenovirus does not directly invade liver cells, but indirectly damages the liver by causing immune system disorders?” The article in the New England Journal of Medicine on July 13 once proposed this assumption.
Two new British studies answer this question.
A possible genetic risk factor has been identified by the University of Glasgow. Of the 20 patients, 17 carried a specific HLA genotype (DRB1*04:01) .
This is a genetic variation. Studies have shown that people with this genotype are more likely to develop an “excessive immune response” after viral infection.
Science says the genetic mutation is particularly common in northern Europeans. 11% of Britons are carriers, and the detection rate in Scotland may reach 15.6%.
The UK is the first country to report cases of unexplained childhood hepatitis to the World Health Organization (WHO) . The country’s first cases were in Scotland.
The two UK studies mentioned above have not been peer-reviewed.
Angela Rasmussen , a virologist at the University of Saskatchewan in Canada, has pointed out that acute hepatitis of unknown cause in children may be the product of a combination of “three elements”, including a helper virus (such as adenovirus) , AAV2 and genetic susceptibility (specific HLA genotypes).
Saul Karpen, a pediatric gastroenterologist at Emory University School of Medicine in the United States, and others said that the relevant theory deserves further study, but it is still inconclusive.
Angela Rasmussen and Sol Calpan said that these studies are only a very small number of cases and controls, and may be an association rather than a causal relationship.
What impact does this have on the clinic?
According to the WHO report, as of July 8, 2022, a total of 1,010 cases of acute hepatitis of unknown cause in children and at least 22 deaths have been reported in 35 countries and regions around the world.
The aforementioned research has certain implications for clinical practice. If there is a case, we know where to look for the cause and symptomatic treatment.
When the cause is unknown, the treatment will be slightly passive.
For example, if liver function is damaged due to inflammation, anti-inflammatory drugs can be used. If liver failure occurs, liver transplantation should be considered.
According to WHO data, 46 related children worldwide need liver transplantation.
After confirming the incentives, you can find ways to prevent them from the source.
 Adeno-associated virus 2 infection in children with non-AE hepatitis.medRxiv
GENOMIC INVESTIGATIONS OF ACUTE HEPATITIS OF UNKNOWN AETIOLOGY IN CHILDREN.medRxiv
New studies offer theory on cause of unusual hepatitis cases in kids.STAT
Mystery hepatitis cases in kids linked to unexpected viral suspect.Science.doi:10.1126/science.ade1120
 Expert advice on the diagnosis and treatment of severe acute hepatitis in children of unknown cause. Chinese Journal of Pediatrics. DOI: 10.3760/cma.j.cn112140-20220510-00435
Unexplained hepatitis in children is not necessarily an infectious disease
(source:internet, reference only)