Why does hepatitis in children of unknown cause appear? Experts speculate that long-term isolation affects childhood immunity

Unexplained childhood hepatitis has been reported in at least 12 countries worldwide, and the cause is not yet clear.

According to the official WeChat public account "Huashan Infection" of the Huashan Medical Infection Department affiliated to Fudan University on April 29, experts such as Xie Youhua, executive deputy director of the Medical Molecular Virology Health Commission of Fudan University and the Key Laboratory of the Ministry of Education, posted an article speculating that the unexplained childhood hepatitis may be caused by new variants of adenovirus; at the same time, the prevention and control of the new crown epidemic may cause some young children to have reduced contact with common pathogens, resulting in the development of their immune systems different from that of children of the same age before the new crown epidemic, even if infected with common pathogens such as adenoviruses. It can also produce an immune response or disease manifestation that is different from that of previous peers. In addition, the article also gives other speculations.

Zhang Wenhong, director of the Department of Infectious Diseases at Huashan Hospital affiliated to Fudan University, made a related comment, "At present, it is speculated that it is a long period of new crown isolation, children have not been exposed to this virus (adenovirus) for a long time, and sudden contact will produce more serious immune damage, which is consistent with the phenomenon that emerging infectious diseases tend to be heavier in the early stage of disease outbreaks." ”

The article also reminds that due to the imported risk of the disease, it is necessary to prepare early, and parents should pay attention to children's hand hygiene.

Experts speculate on the possible cause of this hepatitis from 4 aspects

On April 29, the public number of "Huashan Infection" launched the article "Outbreak and Causes of Hepatitis in Children of Unknown Causes in the United Kingdom and Other Places", written by Xie Youhua and others.

As of 21 April, 12 countries worldwide have reported 169 cases of unexplained hepatitis in children, including 114 cases in the United Kingdom, 13 cases in Spain, 12 cases in Israel, 9 cases in the United States, 6 cases in Denmark, 5 cases in Ireland, 4 cases in the Netherlands, 4 cases in Italy, 2 cases each in Norway and France, and 1 case each in Romania and Belgium. Children range from 1 month of age to 16 years of age.

Hepatitis of unknown origin presents clinically as acute hepatitis, with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 500 IU/L, and most children have jaundice, nausea, abdominal pain, fatigue, drowsiness, and gastrointestinal symptoms, including diarrhea and vomiting. Most children are fever-free. Seventeen patients underwent liver transplants and at least one death was reported.

The article said that all children with unexplained hepatitis in the UK have not been vaccinated against COVID-19, so the direct correlation between the vaccine and hepatitis in unexplained children can be ruled out. Taking into account the epidemiological characteristics and the clinical characteristics of the child, infectious factors are more likely to cause the disease. Laboratory findings in all cases have ruled out hepatitis A, B, C, D, and E, suggesting that adenovirus may be associated with unexplained childhood hepatitis, but other infectious or environmental factors are not completely excluded.

The paper argues that although it is currently speculated that adenovirus infection may be one of the potential factors contributing to severe acute hepatitis in children, it is not yet possible to explain the severity of its clinical symptoms. Adenovirus is a common human pathogen, and adenovirus infections are usually self-limiting and cause only mild illness or symptoms. Acute hepatitis caused by adenovirus infection is uncommon, especially in immunocompetent children, although there have been case reports of hepatitis developing after infection with adenovirus in immunocompromised children.

In view of the current situation, the article speculates that 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.

Be wary of input risks and do a good job of personal protection

According to the news of the "Huashan Infection" public number on April 29, Zhang Wenhong made relevant comments on the article.

He noted that "cases of hepatitis of unknown cause occur every year, often referring to liver damage caused by known hepatitis viruses or known causes, which is not uncommon in children". The question at hand is, "There is a correlation with adenovirus infection that has been found so far, but adenovirus infection is a very common phenomenon that can cause pneumonia or diarrhea, so why are so many cases of severe hepatitis this year, and only in children?" ”

"The current speculation is that there is a long period of COVID-19 isolation, children have not been exposed to the virus for a long time, and sudden contact will produce more serious immune damage, which is consistent with the phenomenon that emerging infectious diseases tend to be heavier in the early stages of disease outbreaks." Zhang Wenhong explained. He further analyzed, "If it is caused by this cause, rather than a new virus that has not been detected before, the subsequent effects of this unexplained hepatitis will gradually decline." ”

Zhang Wenhong also reminded, "We also need to be vigilant against unknown pathogens, even if the probability of such an emerging infectious disease pandemic is not high." In addition, as awareness continues to deepen, the definition of the current confirmed case is also constantly being updated. ”

The authors also caution that "because of the imported risk of the disease, it is necessary to prepare for it." As far as personal protection is concerned, the authors remind that "the mainland is still in an important stage of active prevention and control of the COVID-19 epidemic, and in the context of promoting the development of good personal hygiene habits, parents especially need to care about children's hand hygiene." ”