Why does unexplained childhood hepatitis occur? Experts speculate that it may be because...

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For hepatitis in children of unknown cause, experts give a variety of speculations...

Recently, at least 12 countries around the world have reported unexplained childhood hepatitis, and the cause is not yet clear. The World Health Organization released a report on the 23rd that of the 169 cases of hepatitis in children of unknown etiology found worldwide, 74 cases of adenovirus tested positive. Among them, 18 cases were identified as adenovirus type 41, 20 children were detected with SARS-CoV-2, and 19 cases were co-infected with adenovirus and SARS-CoV-2. Adenovirus is currently a hypothesis of etiology, but it does not fully explain the severity of clinical symptoms.

Children present clinically with acute hepatitis, elevated levels of transaminases in the blood (AST or ALT>500 IU/L), and many children have jaundice, nausea, abdominal pain, fatigue, and drowsiness. Some children report gastrointestinal symptoms, including diarrhea and vomiting, in the weeks leading up to admission. Most children do not have fever.

For the causes of such hepatitis, many experts have given different speculations...

Health Commission of Medical Molecular Virology of Fudan University

and Executive Deputy Director of the Key Laboratory of the Ministry of Education

Experts such as Xie Youhua speculate that there are 4 possibilities

Xie Youhua, executive deputy director of the Health Commission of Medical Molecular Virology of Fudan University and the Key Laboratory of the Ministry of Education, pointed out in the official WeChat public account "Huashan Infection" on April 29 that all children with unexplained hepatitis in the UK have not been vaccinated against the new crown vaccine, so the direct correlation between the vaccine and hepatitis in children of unknown cause can be ruled out. At the same time, through investigation, no common toxic factor exposure was found. Although toxicological investigations are still ongoing, it is speculated based on epidemiological features and the clinical features of the case that infectious factors are more likely to cause the disease. Laboratory findings in all reported cases excluded hepatitis A, B, C, D and E.

Of the 169 cases published by the World Health Organization, 74 children tested positive for adenovirus, of which 18 were identified as adenovirus type 41. 20 cases of children were tested for the new crown virus, and 19 cases were co-infected with adenovirus and the new crown virus. In addition, norovirus, rhinovirus, enterovirus, parainfluenza virus, etc. have been detected in individual cases.

Although it has been speculated that adenovirus infection may be one of the potential factors contributing to severe acute hepatitis in children, it is not possible to explain the severity of its clinical symptoms.

Adenovirus is a common human pathogen, a double-stranded DNA virus, divided into 7 subgroups of more than 50 serotypes, mainly through respiratory tract and contact to spread from person to person, often causing respiratory diseases.

Through analysis and speculation, at present, the possible causes of hepatitis in children of unknown origin are as follows:

1. It is a new variant of a known virus, which may be adenovirus, but it cannot rule out the possibility of other pathogens, such as coronavirus, rhinovirus, enterovirus, parainfluenza virus and other variant strains. If it is a new variant of adenovirus, it is worth paying attention to whether it is related to the recombination and mutation of adenovirus under the selection pressure that may occur after mass vaccination of adenovirus vector vaccine.

2. The prevention and control of the epidemic during the COVID-19 epidemic may cause some young children to have reduced contact with common pathogens, resulting in the development of their immune systems different from those of children of the same age before the COVID-19 epidemic. When young children are subsequently infected with common pathogens such as adenovirus, they have a different immune response or disease manifestation than their previous peers; it is also possible to have a subsequent infection with adenovirus or other viruses based on previous SARS-CoV-2 infection, or sars-CoV-2 co-infection with adenovirus or other viruses.

3. There is a new pathogen that has not yet been discovered.

4. Non-infectious factors, such as environmental toxins and drugs, cannot be completely ruled out.

Ma Anlin, director of the Department of Infectious Diseases at the China-Japan Friendship Hospital

Three possibilities are proposed

Ma Anlin, director of the Department of Infectious Diseases of the China-Japan Friendship Hospital, said in an interview with the Central Broadcasting Network reporter that adenovirus type 41 only provides a clue to find the cause of hepatitis in children of unknown causes, and it is not certain that adenovirus type 41 can cause hepatitis in children. Adenovirus is a common pathogen, from the currently known research results, adenovirus is mainly transmitted through the respiratory tract and contact between people, mainly invades the mucous membrane of the upper respiratory tract, causing respiratory diseases, mainly manifested as fever, runny nose, nasal congestion, sore throat and other symptoms.

Ma Anlin believes that the reason why there is "adenovirus is only the construction of the cause" is because in the cases that have been found, there are patients infected with adenovirus. There are dozens of different serotypes of adenoviruses, and patients infected with different subtypes of adenoviruses may experience different symptoms. Adenovirus infection can usually be prevented by washing hands frequently and disinfecting appropriately.

"In the past, there was no such thing as an adenovirus causing hepatitis." For this hypothesis released by the World Health Organization that adenoviruses cause hepatitis in unknown children, Ma Anlin proposed three possibilities:

1. Adenovirus infected by children with unexplained childhood hepatitis may be a subtype after adenovirus mutation, which may invade the body, including liver, thymus, lymph and other organs. From an adenovirus perspective, this new subtype may have a greater impact on the liver;

2. According to the age of sick children published by the World Health Organization, children between the ages of 1 month and 16 years old are mostly in the blank immunization period, unlike adults, children in the blank immunization period have a strong immune response after infection with adenovirus, excessive immunization occurs, which leads to hepatitis due to explosive liver damage;

3, is there may also be other factors caused by hepatitis, adenovirus is a common virus, mainly manifested as upper respiratory tract symptoms, in many children can be isolated adenovirus.

Will there be a pandemic?

Expert: Unlikely

Chang Rongshan, a virology expert, believes that it will not cause a large-scale epidemic, but there is a possibility of endemic epidemics. Most people in China have been infected with various subtypes of adenovirus, and adults have pre-existing antibodies to various epidemic strains of adenovirus, and they are also immune to other subtypes. In contrast, adenoviruses are more likely to circulate in children because there are fewer pre-stored antibodies in children.

Chang Rongshan said, "I analyzed the age data of these cases, more than 80% of them are children under 5 years old, 5-11 years old children account for very little in this hepatitis, 11-16 years old account for even less, did not find adults with such hepatitis, but also from the side to illustrate this reasoning." ”

At present, no cases of hepatitis of unknown cause have been reported in the country. On April 27, the Beijing Municipal Health Commission issued the Notice on Strengthening the Treatment of Children's Hepatitis Cases of Unknown Cause, prompting medical institutions to pay attention to children with hepatitis caused by unknown causes, and if such cases occur, they should find out the causes and strengthen treatment as soon as possible.

Resources:

Huashan infection "Outbreaks and causes of hepatitis in children of unknown cause in the United Kingdom and other places", the original article was published in the journal "Microbiology and Infection", authors: Xie Youhua, Chen Jieliang, Wang Yongxiang, Yuan Zhenghong

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