Dialogue with British virologist
What's known and what's unanswered about hepatitis of unknown etiology
Since the beginning of this year, there has been an abnormal increase in cases of childhood hepatitis of unknown etiology around the world.
The World Health Organization said on May 27 that the number of reported cases of hepatitis of unknown etiology in many countries and regions increased to 650, and the cumulative number of children with hepatitis of unknown etiology in the United Kingdom increased to 222. It is currently the country with the most reported cases and the first to report related cases. s country.
Well-known virologist and professor of virology at the University of Nottingham in the United Kingdom, Will Owen, told the Beijing News that there are currently multiple etiological hypotheses, adenovirus infection is only one of them, and the new coronavirus is unlikely to directly cause liver damage, and relevant investigations are underway. processing.
Faced with what appears to be a more serious virus threat, Irving said it won't be long.
What do we already know about hepatitis of unknown etiology?
How many truths remain to be solved?
Adenovirus F41 has not been previously associated with liver damage
Beijing News: What is the current situation in the UK regarding hepatitis of unknown etiology?
Will Owen: At this stage, we are still investigating multiple possible causes, and adenovirus infection is just one of them.
Available data suggest that children are most likely to be infected with adenovirus.
Normally, adenovirus does not cause hepatitis, but oddly, it is detected in about three-quarters of cases of hepatitis of unknown etiology in the UK.
We are also not sure whether adenovirus infection is responsible for liver damage.
If adenovirus infection has caused liver damage, we can't help but ask, why did this happen in 2022 if adenovirus has not caused liver damage in the past 50 years?
Beijing News: In addition to the United Kingdom, the United States has also set its sights on adenovirus F41. What do you think?
Will Owen: The F41 adenovirus detected so far is unusual because the virus has not previously caused liver damage.
The Beijing News: The British Health and Safety Agency has put forward the hypothesis that the unexplained hepatitis cases are caused by the mutation of the adenovirus gene. What do you think?
Will Owen: Still need more data to support.
Although adenoviruses have been isolated from some cases of childhood hepatitis of unknown etiology in the UK, the numbers are small, making sequencing the viral genome difficult.
It's important to try to get more genetic sequence data from viruses and compare with similar virus sequences from previous years, but we don't fully have that data yet.
Beijing News: What other evidence is needed to determine the cause?
What are the underlying causes?
Will Owen: Research is underway to find the cause based on metagenomics approaches.
In specimens of hepatitis of unknown etiology, we have found and are sequencing adenoviruses to determine if there is something special about these adenoviruses that mutates to some extent from previous years to be able to infect the liver and cause liver damage.
In addition to the above-mentioned etiological hypothesis, countries such as the United Kingdom have also carried out epidemiological studies, by communicating with children and their parents with hepatitis of unknown etiology, trying to understand whether this type of hepatitis is exposed to a certain drug, certain toxin, food Supplements, etc.
The cause of hepatocyte necrosis has not yet been determined
Beijing News: Why is it so difficult to determine the cause?
Where is the difficulty?
Will Owen: A certain substance causes liver damage and causes liver cell necrosis, but the cause of liver cell necrosis cannot be identified at present. This is the primary difficulty in determining the cause.
Hepatocyte necrosis may be caused by a substance (such as a drug, toxin, or virus) directly damaging the liver, or by infection with a substance that causes the patient's immune system to attack the liver, known as autoimmune hepatitis.
By observing liver specimens from 11 children with hepatitis of unknown etiology in the UK, we did not see any virus particles in the liver cells, but there seemed to be infiltration of inflammatory cells in the liver, but the nature of these inflammatory cells could not be determined for the time being. Causes of hepatocyte necrosis.
In addition, hepatocyte necrosis may also be caused by infection with a substance whose characteristics have not been identified before, and we do not know the characteristics of the substance, let alone where to start, and it is extremely difficult to find the cause of hepatocyte necrosis.
There are also hypotheses that the new coronavirus causes abnormal immune responses in children after they have recently been infected with the new coronavirus; there are also hypotheses that the risk of infection in children may have increased due to the new crown epidemic prevention measures in the past two years.
Although there are many hypotheses about the etiology, what we can do at this stage is to speculate on the cause of liver injury and try to collect the necessary evidence before drawing a final conclusion.
New coronavirus unlikely to directly cause liver damage
Beijing News: An article published in the British medical journal "The Lancet Gastroenterology and Hepatology" recently proposed a hypothesis on the pathogenic mechanism. This kind of hepatitis may be related to the immune activation mediated by the new coronavirus superantigen. related, and induced disease due to co-infection with adenovirus.
What do you think?
Will Owen: In the UK, only a very small number (less than a quarter) of children with hepatitis of unknown etiology have evidence of Covid-19 infection on admission.
This type of hepatitis is unlikely to be the result of the direct action of SARS-CoV-2, in other words, SARS-CoV-2 is unlikely to directly cause liver damage.
It is hypothesized that cases of hepatitis of unknown etiology may have contracted Covid-19 six months earlier, which altered their immune systems so that these cases responded abnormally to other common childhood viruses later on. The immune systems were not fighting off the virus, Instead, the virus is transferred to the liver, where it can be damaged.
This is a perfectly reasonable assumption that is difficult to prove.
One of the reasons why it is difficult to prove is that the population rate of new crown infection is very high, and more data are needed to prove that children with unexplained hepatitis are more likely to have contracted the new crown before contracting such hepatitis.
It has not been proven that hepatitis of unknown etiology is easily contagious
The Beijing News: There have also been reports of hepatitis of unknown etiology around the world. Why is this hepatitis of unknown etiology aroused concern?
Will hepatitis of unknown etiology reproduce the new crown pandemic?
Will Owen: There are always very few children with severe liver damage, but the cause has never been found.
The UK used to report around 20 cases of hepatitis of unknown etiology each year, but in the first four months or so of this year 180 cases have been reported.
The number of cases has increased significantly, but the etiology is not clear, so everyone is highly concerned.
However, there are already signs in the UK that hepatitis of unknown etiology is not a readily transmissible disease.
If hepatitis of unknown etiology is easily transmitted, the number of cases should increase dramatically over a short period of time, which is not the case in the UK.
For weeks, the UK has seen a steady increase in the number of new cases with six new cases a week, rather than a sharp rise in the hundreds or thousands.
Next, the increase in the number of unexplained hepatitis cases in the UK is also likely to slow.
Hospitals can offer adjuvant therapy to help keep the liver alive
Beijing News: How long does it take to determine the cause?
Will Owen: How long it ultimately takes to determine the cause depends on the results of the experiment.
In the next two or three months, hopefully we can find the cause, but also consider the possibility of not finding the cause.
If the cause is unclear, it is hoped that this type of hepatitis will go away on its own.
Beijing News: What are the current treatment options?
Will Owen: Without knowing the exact cause, it is impossible to formulate a precise treatment plan, but hepatitis with unknown cause has already hurt children, their livers are damaged, and they need to go to the hospital for medical treatment.
For the hospital, the hospital can provide adjunctive therapy to maintain fluid balance, ensure normal blood clots, and ensure that there are no problems with blood, sugar, and nutrients.
Through adjuvant therapy, the hospital helps patients maintain liver vitality and promote liver cell regeneration in a relatively healthy state.
After adjuvant therapy helps the patient stabilize various vital signs, the next step is to wait for the liver to recover on its own.
Beijing News: How to prevent hepatitis of unknown etiology?
Will Owen: Hand hygiene, respiratory hygiene is recommended.
Also, don't worry parents, the total number of cases in the UK is still very low, with very few cases so severe that they require a liver transplant.
Parents should seek medical help right away if they are concerned, especially if their child shows any signs of this type of hepatitis of unknown cause.
Is humanity facing a growing virus threat?
Beijing News: In addition to hepatitis of unknown etiology, the number of monkeypox cases has also increased abnormally. These two viruses have existed in the past, but this time they are still rare. Is this related to the new crown pandemic?
Will Owen: The monkeypox outbreak is something to watch.
The spread of monkeypox was caused by various people traveling and vacationing around the world, including in Africa, where the monkeypox virus is prevalent, or by someone who had been to Africa and brought it back to their home country.
People who carry monkeypox virus gather together and spread monkeypox virus after close contact with others.
The spread of many viruses has accelerated recently and is likely to accelerate further in the coming months.
My concern now is that there could be a massive relapse of the flu this winter.
Influenza outbreaks occur almost everywhere in the world every winter, but the past two years have seen low rates of influenza.
With the relaxation of the new crown epidemic prevention measures, people may experience a large-scale recurrence of influenza this winter, and many people may become ill or even die from the flu.
Beijing News: Does this constitute a trend that people may face more serious virus threats in the future?
Will Owen: It's not going to be a lasting phenomenon.
The number of viral infections may increase in the future, but not forever.
This year is a special year, people are trying to get out of the pandemic, and in about a year, we will be back to where we were before the pandemic, with different exposures, including the flu, to the same extent as before.
12 Questions and Answers about Hepatitis in Children of Unknown Cause
Cases of childhood hepatitis of unknown etiology have been reported in several countries and territories around the world since the UK first reported it on 5 April 2022.
What is childhood hepatitis of unknown etiology?
How severe are the symptoms?
How to prevent?
12 questions to give you a comprehensive understanding of childhood hepatitis of unknown etiology.
Beijing News reporter Zhu Yuehong
What is hepatitis of unknown etiology?
On May 7, the National Health Commission said in response to a question about childhood hepatitis of unknown etiology that the common characteristics of children with acute hepatitis are: ①Age from 1 month to 16 years old, most of them are under 10 years old; ②The appearance of jaundice and nausea , abdominal pain, fatigue, lethargy and gastrointestinal symptoms (including diarrhea and vomiting), most of the children without fever; ③ laboratory liver biochemical examination of transaminase (AST or ALT) significantly increased.
What is the global prevalence of childhood hepatitis of unknown etiology?
On May 27, local time, the World Health Organization issued a notification on hepatitis of unknown etiology. From April 5 to May 26, 33 countries and regions reported to the World Health Organization 650 cases of suspected acute hepatitis of unknown cause in children. case.
The National Health and Medical Commission said on May 7 that no relevant cases have been found in my country, and health administrative departments and medical institutions at all levels are closely monitoring and continuously monitoring the relevant situation.
Which countries and regions in the world have suspected cases of hepatitis of unknown etiology found?
According to a notification updated on the World Health Organization's official website on May 27, most of the suspected cases came from countries in the European Region of the World Health Organization.
Specifically, countries and regions reporting hepatitis of unknown etiology include: Belgium 14, Canada 10, Denmark 7, Ireland 7, Israel 12, Italy 27, Japan 31, Mexico 10, and the Netherlands 14 11 cases in Portugal, 29 cases in Spain, 9 cases in Sweden, 222 cases in the United Kingdom, and 216 cases in the United States.
Other countries and regions with less than 5 cases of hepatitis of unknown etiology include: Argentina, Austria, Bulgaria, Cyprus, France, Greece, etc.
How severe is the disease in children with hepatitis of unknown etiology?
According to data provided by the World Health Organization, among at least 650 suspected cases of acute hepatitis of unknown etiology in children, at least 38 require liver transplantation, and there have been 9 deaths, 75.4% of which are younger than 5 years old.
Is there a link between globally reported cases of hepatitis of unknown etiology?
The World Health Organization said most of the reported cases appeared to be unrelated, and extensive epidemiological investigations were underway to identify common contacts, risk factors or links between cases.
Two pairs of cases in Scotland have been reported as epidemiologically linked, and similar reports have been reported in the Netherlands.
The European Center for Disease Control and Prevention once said in an interview with a reporter from the Beijing News that among the countries reporting cases, most of them are sporadic cases, and there is no connection between the cases.
What makes this unexplained hepatitis unusual?
According to the World Health Organization, compared with previous childhood hepatitis of unknown etiology, the clinical symptoms of children with unknown etiology are more severe this time, and the possibility of acute liver failure is higher, but the cause is still unclear.
How should we treat hepatitis of unknown etiology?
The World Health Organization says that although hepatitis of unknown etiology is still rare, it should be taken seriously.
It is imperative to identify the cause so that control and preventive measures can be further refined.
What are the current major hypotheses regarding etiology?
The etiology and pathogenesis of unknown hepatitis are still under investigation, and common hepatitis virus (hepatitis A, B, C, D, and E virus) infection is currently excluded.
Adenovirus infection was the main hypothesis.
Adenovirus is a common virus that spreads from person to person, and adenovirus infection usually causes vomiting and diarrhea in children, along with respiratory symptoms.
The World Health Organization said that while adenovirus was a hypothesis as the underlying cause, it did not fully explain the severity of the clinical situation, and the finding that the etiology was clearly associated with adenovirus may have been incidental, as the increase in laboratory detection of adenovirus comes at a time when It was at a time when community transmission of adenovirus was on the rise.
Is hepatitis of unknown etiology related to the new crown?
The UK's Health Security Agency has suggested that prevention measures during the new crown pandemic may reduce the chance of children being directly exposed to the virus, making them more susceptible to hepatitis of unknown cause.
The international authoritative academic journal "The Lancet Gastroenterology and Hepatology" released the latest report, which pointed out that more than 300 cases of childhood hepatitis of unknown etiology found in more than 20 countries may be related to the superantigen caused by the new coronavirus.
According to a recent survey by the World Health Organization, since the vast majority of children with unexplained acute hepatitis have not been vaccinated against the new coronavirus, the hypothesis related to the vaccination of the new coronavirus is not currently supported.
Why is the risk level for hepatitis of unknown etiology adjusted to intermediate?
The World Health Organization has adjusted the disease risk level for hepatitis of unknown etiology to intermediate for the following reasons:
Limited epidemiological, laboratory, histopathological, and clinical information is currently available; the actual number of cases may be underestimated in some cases; due in part to limited surveillance capacity available, the source and mode of transmission of potential pathogens have not yet been determined Therefore, the possibility of further transmission cannot be fully assessed; although there are no medical reports of mutual transmission between cases, human-to-human transmission of hepatitis of unknown etiology cannot be ruled out because there are some reports of epidemiologically relevant cases.
How to prevent hepatitis of unknown etiology?
The World Health Organization recommends frequent hand washing and respiratory hygiene to prevent common viral infections such as adenovirus.
Until more information is available, general infection prevention and control measures are recommended, including maintaining hand hygiene with soap and water or an alcohol-based sanitizer; following safe food handling and cooking practices.
The National Health and Health Commission stated that at present, the main preventive measures are to prevent children from going to crowded public places with poor ventilation, cut off contact with droplets and fecal-oral transmission routes, ensure that children have adequate sleep and nutrition, and regularly wash children's clothes and regular clothes. Contact with objects, wash hands frequently, wear masks, and maintain social distance. If children have hepatitis symptoms such as jaundice and gastrointestinal symptoms, they should seek medical attention in time.
How to detect hepatitis of unknown etiology in time?
Several experts from the Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences jointly suggested that since the cause of the disease is still unclear, it is recommended that the suspected cases should be managed during the isolation period during the diagnosis and treatment process, and the feces, secretions, excrement and blood pollutants of the patients should be strictly disinfected deal with.
The National Health and Health Commission stated that if the child has symptoms consistent with hepatitis of unknown etiology, parents should be vigilant and go to the hospital in time. To further determine whether the child has acute hepatitis and possible causes.
Beijing News reporter Zhu Yuehong and Yao Yuan