Source 丨21 Healthnews21 original work
Author 丨 Wei laughs
Editor 丨 Xu Xu
Picture 丨 Figure Worm
Cases of hepatitis of unknown origin continue to increase globally.
To date, nearly 200 cases have been reported from at least 13 countries worldwide. Among them, Japan reported the detection of the first case in Asia. According to Japanese media reports, on April 28, Japan's Ministry of Health, Labor and Welfare said that the country reported 2 new cases of acute hepatitis in children of unknown cause, plus one case reported on April 25, and there were 3 cases of acute hepatitis in children of unknown cause in Japan.
As of April 28, at least 20 cases of hepatitis in children have been reported in the U.S. states of Alabama, Delaware, Illinois, New York, North Carolina and Wisconsin, including at least four children in need of liver transplantation and one child who has died.
In this regard, Zhang Wenhong, director of the National Center for Infectious Diseases And director of the Department of Infectious Diseases of Huashan Hospital affiliated to Fudan University, commented that the unexplained hepatitis that WHO is concerned about this time has the characteristics of cluster incidence, and the incidence rate is beyond previous years, and it is reasonable to consider the risk of infectious diseases. "If it is caused by a prolonged isolation of the new crown, rather than a new virus that has not been discovered before, the subsequent effects of this unexplained hepatitis will gradually decline, but we also need to be vigilant against unknown pathogens, even if the probability of this emerging infectious disease pandemic is not high."
Recent studies have shown that mRNA vaccination may lead to the development of hepatitis. In response, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) published an article saying that the available evidence does not support a causal relationship between the new crown mRNA vaccine and very rare cases of autoimmune hepatitis (AIH).
In addition, there is currently no evidence that the COVID-19 vaccine has been linked to cases of unexplained hepatitis in children. WHO said it does not currently support hypotheses related to the side effects of the COVID-19 vaccine, as most of the affected children are too young to be vaccinated.
Unexplained hepatitis is possible in four ways
According to WHO, the first children were all located in the UK and were detected during hospitalization, with the earliest case being in January this year.
The U.S. investigation set a new time record. According to STAT, the United States has identified 9 cases of unexplained acute hepatitis in children, all reported by Alabama, with children ranging in age from 1 to 6 years. The earliest case was admitted to the hospital in the fall of 2021.
In the UK, children are concentrated in 2-5 years of age, and the main symptoms are vomiting, jaundice and yellowing of the whites of the eyes. The earliest batch of clinical data released by local researchers in Europe Monitor on April 14 showed that most children had blood levels of alanine transaminases (ALT) exceeding 2,000 IU/L, while normal values should be 10-40 IU/L.
The WHO report also indicates that the clinical syndrome in these cases is characterized by acute hepatitis, markedly elevated aminotransferases, usually with jaundice and sometimes with gastrointestinal symptoms.
Notably, just a week before the onset of illness, the children were healthy, and clinical records indicate that the children did not have any significant past medical history, such as underlying immunodeficiency or treatment with immunosuppressants.
However, the cause of this hepatitis is not yet clear. Hepatitis A, B, C and E virus infection was ruled out after several typical hepatitis virus tests were performed on children in the UK and Spain. Because most children do not have fever or abnormal markers of blood inflammation, C-reactive proteins, and elevated white blood cell counts, only a small percentage of children are bacteriologically tested and no abnormalities are reported.
After that, the scientists further expanded the detection range of viruses to those that are not within the scope of routine detection of hepatitis, such as enterovirus, paraintestinal virus, human herpesvirus 6, 7, varicella zoster virus, adenovirus. Eventually, they found that 5 of the 13 Scottish children published in Europe Surveillance tested positive for adenovirus, and officials from the Alabama Department of Public Health in the United States also confirmed in interviews that 5 of the 9 sick children in the local area were positive for adenovirus-41.
Meanwhile, UK Health Security Agency data shows that 77% of cases test positive for adenovirus. Mira Chand, who heads clinical and emerging infections at the UK Health Safety Service, noted that survey data are increasingly revealing that this (hepatitis) is linked to adenovirus infection. However, we are thoroughly investigating other possible factors.
WHO says countries are strongly encouraged to identify, investigate and report potential cases that meet the definition. The so-called "conformity to the definition" includes 3 aspects.
First, the confirmed case, i.e. after 1 January 2022, aged 10 years and below, has acute hepatitis (not caused by A, B, C, D or E virus infection) and aspartate aminotransferase (AST) or alanine transaminase (ALT) > 500U/L. In contrast, the normal ALT value should be 10-40 IU/L.
Second, the suspected case, i.e. after 1 January 2022, aged 11-16 years, with acute hepatitis (not caused by A, B, C, D, or E virus infection) and AST or ALT > 500U/L.
Third, epidemiologically related cases: after 1 January 2022, there was acute hepatitis (not caused by A, B, C, D or E virus infection) and had close contact with the confirmed case.
The official WeChat of the Department of Infectious Diseases of Huashan Hospital affiliated to Fudan University in Shanghai pointed out that at present, the possible causes of hepatitis in children of unknown cause speculated are as follows:
First, 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 variants of coronavirus, rhinovirus, enterovirus, parainfluenza virus, etc. 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.
Second, epidemic prevention and control during the COVID-19 pandemic may result in reduced exposure of some young children to common pathogens, resulting in a different development of their immune systems than children of the same age before the COVID-19 pandemic. 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.
Third, there is a new pathogen that has not yet been discovered.
Fourth, non-infectious factors, such as environmental toxins and drugs, cannot be completely ruled out.
In this regard, Zhang Wenhong commented that cases of hepatitis of unknown cause occur every year, often referring to liver damage caused by known hepatitis virus or known etiology, which is not uncommon in children. However, hepatitis of unknown cause of concern to WHO this time has the characteristics of cluster incidence, and the incidence rate is higher than in previous years. In this case, it makes sense to consider the risk of infectious diseases.
Zhang Wenhong said that there is a certain correlation with adenovirus infection. But adenovirus infection is a very common phenomenon and can cause pneumonia or diarrhea, so why are there so many cases of severe hepatitis this year, and only in children? At present, it is speculated that it is a long period of new crown isolation, children have not been exposed to this 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 believes that if it is caused by a long period of new crown isolation, rather than a new virus that has not been discovered before, the subsequent effects of this unexplained hepatitis will gradually decline, but we also need to be vigilant against unknown pathogens, even if the probability of this 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.
Lu Hongzhou, head of the first public health expert group on epidemic prevention and control in Shenzhen and president of the Third People's Hospital of Shenzhen, also pointed out in an interview with the 21st Century Business Herald reporter that in fact, all ages are susceptible to adenovirus, but because children's immune systems are not well developed and their resistance is poor, they are more susceptible to infection. In addition, infection with adenovirus does not generally cause severe acute hepatitis, but in immunocompromised patients can cause occasional or severe viral infections, especially in some organ transplant patients.
There is no evidence that the COVID-19 vaccine causes hepatitis in unknown children
WHO predicts that the number of cases of hepatitis in unexplained children is likely to continue to increase in the future, and with the release of more case data and laboratory test results, many questions about the etiology of hepatitis in unexplained children may be answered, allowing for more targeted prevention and control measures.
It is worth noting that on April 21, 2022, the Journal of Hepatology, an authoritative international journal in the field of liver disease, published the article "SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatitis". The article points out that the covid-19 mRNA vaccine (BNT162b2) jointly developed by Pfizer/BioNTech may trigger a rare T-cell-mediated autoimmune hepatitis.
The report said a 52-year-old male patient developed acute hepatitis after receiving the COVID-19 mRNA vaccine (BNT162b2), developed jointly by Pfizer/BioNTech. After further research, the researchers believe that vaccinating against BNT162b2 may trigger autoimmune hepatitis (AIH).
Can the mRNA vaccine cause acute hepatitis? In this regard, some insiders stressed that there is no clear evidence that there is a direct and inevitable link between mRNA vaccine and autoimmune hepatitis. "More than a billion doses of mRNA vaccine have been injected worldwide, and several cases of liver inflammation are normal, and they are one case, related to the immune function of individuals. The public does not have to panic, can not be choked up, from the BNT/Pfizer and Moderna has announced side effects and cases, mRNA vaccine is still safe and effective, side effects are controllable. ”
The above-mentioned industry insiders also said that the two mRNA vaccines that have been listed from emergency authorization to full approval are the process of regulatory agencies and vaccine companies to track the safety data and risk assessment of the vaccine after the market, with sufficient data support and regulatory guarantees. "In general, the US CDC will track all the side effects of the vaccine after 18 months of marketing, and if there is a major event, it will ask the vaccine company to track the investigation, supplement the experiment, rectify or even delist."
On April 8, the European Medicines Agency's (EMA) Committee on Pharmacovigilance Risk Assessment (PRAC) published an article saying that the available evidence does not support a causal relationship between the COVID-19 mRNA vaccine and very rare cases of autoimmune hepatitis (AIH).
In fact, there is no evidence that the COVID-19 vaccine is associated with unknown cases of hepatitis, as most children with acute hepatitis are not vaccinated against COVID-19.
WHO said it does not currently support hypotheses related to the side effects of the COVID-19 vaccine, as most of the affected children are too young to be vaccinated.
Lu Hongzhou also believes that hepatitis in children of unknown cause should not be associated with COVID-19 vaccination. "Children have been vaccinated against COVID-19 for a long time, and if it causes hepatitis, it will not appear until recently."