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Writing| Yan Xiaoliu< /strong>Source| “Medical Community” Official AccountMultiple worldwide, unknown etiology, rapid development, serious rule Life-threatening acute hepatitis of unknown etiology in children, outbreak of nearly more than 3 months. The scientific community may finally find the key to the puzzle. This may be the result of multiple factors, according to two independent studies from Scotland and London, UK. On the one hand, a child may be infected with two different viruses at the same time. On the other hand, the patient has a genetic mutation, which may make the immune system “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.” Weibo big V, virus and infectious disease scientist @ Ziling expressed his views on Weibo. say. Or from the synergy of the two virusesThere are many causative hypotheses about acute hepatitis of unknown etiology in children. The theory of human adenovirus(hADV)infection, especially adenovirus type 41, was first proposed and has the most supporters. The New England Journal of Medicine(NEJM) published two case studies on July 13, saying the virus was detected in about 90 percent of the children surveyed. In this regard, two new British studies 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 were detected in the blood and liver tissue of 96% of the children interviewed (AAV2). 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. University of Glasgow, UK finds “possible accomplice”: 86% of children have adenovirus detected in blood or liver tissue(HAdV C/F) , and some children were detected with herpes virus(HHV6B). AAV2, adenovirus and herpes virus are not novel viruses. The University of Glasgow team pointed out that if its hypothesis is correct, a large number of children with unexplained hepatitis in many countries and regions must have their “special background” at the same time. “The current situation comes after the relaxation of the new crown epidemic prevention measures. In the past two years, the transmission of the virus that was interrupted by wearing masks and maintaining social distance has become active again. In addition, in the past two years , children are overprotected and less likely to be exposed to other pathogens, so pre-existing immunity is also reduced. This can lead to more childrenInfection, or promote an increase in childhood hepatitis cases.” US life science website STAT According to the analysis of the research team. This explains why the unknown Causes Acute hepatitis in children occurs in a short period of time, and there is no overlap between children from different countries and regions. “Easing COVID-19 restrictions means that children may be exposed to many viruses at once, rather than gradually being exposed to more viruses.”Special genotypes found strong>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. A multinational epidemiological survey from March to the present shows that more cases of unexplained hepatitis occur in previously healthy infants and young children. “Is it possible that liver damage may be a sequelae of viral infection? Adenovirus does not directly invade liver cells, but indirectly damages the liver by causing immune system disorders?” New England Journal of Medicine 7 The article of March 13 made this assumption. Two new UK studies answer this question. The University of Glasgow has identified a possible genetic risk factor. Among the 20 patients, 17 carried a special 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 gene 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 described above have not been peer-reviewed. University of Saskatchewan virologist Angela Rasmussen (Angela Rasmussen)combined research and pointed out that acute hepatitis of unknown cause may be a “three-element combination” products”, 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, said that the relevant theory deserves further development. research is still inconclusive. Angela Rasmussen and Saul Calpan said that these studiesOnly a very small number of cases and controls may be association rather than causation. What impact does this have on the clinic? According to the WHO report, as of July 8, 2022, a total of 1010 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. There are no related reports in China. However, domestic experts and scholars have been calling for it to pay close attention to its development trend. “The aforementioned research has certain implications for clinical practice. If there is a case, we know from which angles to find the cause and treat it symptomatically.” Li Huajun, an attending physician in the Department of Infectious Diseases, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, told “Medical boundary”. Li Huajun is good at and mainly treats various childhood infectious diseases. He noted that there are many causes of acute hepatitis in children. In terms of infectious factors, A, B, C, D, and E hepatitis virus infection is not the main factor. Adenovirus, enterovirus, cytomegalovirus, respiratory syncytial virus, EB virus and other infections are induced, see more. Li Huajun said that when the cause is unknown, the treatment will be somewhat 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, we can find ways to prevent them from the source.” Li Huajun said, including avoiding children’s exposure to specific viruses. References:[1]Adeno-associated virus 2 infection in children with non-A-E hepatitis.medRxiv[ 2]GENOMIC INVESTIGATIONS OF ACUTE HEPATITIS OF UNKNOWN AETIOLOGY IN CHILDREN.medRxiv[3]New studies offer theory on cause of unusual hepatitis cases in kids.STAT[4]Mystery hepatitis cases in kids linked to unexpected viral suspect.Science.doi:10.1126/science.ade1120[5] Expert advice on diagnosis and treatment of severe acute hepatitis in children of unknown cause. Chinese Journal of Pediatrics. DOI: 10.3760/cma. j.cn112140-20220510-00435.
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