Does the common virus cause sudden liver failure in children?

Last October, a young girl with severe liver failure was admitted to a hospital in Birmingham, Alabama. His symptoms were typical. skin և eyes yellow with jaundice, markers of liver damage outside the charts. But he gave a negative test for all the usual suspects behind him liver disease. Surprisingly, his only positive test was the adenovirus, a common virus best known for causing colds, pink eyes, or stomach flu. In rare cases, it is associated with hepatitis or inflammation of the liver in immunocompromised patients. But this girl was healthy.

Then it happened again. The second child came, about the same age, with all the same symptoms, again positive for adenovirus. “One patient is accidental. “Both are examples,” said Marcus Buchfelner, a pediatric infectious disease physician at the University of Alabama (UAB) in Birmingham. Two quickly became three, then four. The doctors of the disturbed hospital called the local health authorities և CDC, whose investigation finally found out. nine such cases Unusual hepatitis in children in Alabama. Two needs for liver transplantation.

Buchfelner originally believed that what was happening was happening in Alabama. But this springInvestigators in the UK have begun to wonder about the mysterious rise of hepatitis in children. They have since discovered more than that 150 such cases In the UK, this prompted the CDC to launch a wider network, raising the number of suspected cases in the US up to 109:. Fifteen of the children needed a liver transplant, and five died. All over the world, probable cases are now common 348 were distributed in 20 countries.

Early evidence continues to point to an adenovirus link, an unexpected ratio that is too strong to ignore, not strong enough to close the case. Seventy percent of the world’s cases are positive for adenovirus according to the World Health Organization. However, although biopsies were performed in a small number of cases, they could not detect adenovirus in the liver of children. At the same time, we know for a fact that another virus recently infected a large number of children, SARS-CoV-2, of course. However, here the ratio is even less clear. Only 18% of probable cases gave a positive result to COVID.

Adenovirus ոն coronavirus do not have to be mutually exclusive explanations. Leading hypotheses now suggest an interaction between the adenovirus ‘epidemic’, or because social distance has changed adenovirus’s immune systems, allowing for more severe or simply more: Adenovirus infections or because a previous infection or co-infection with a coronavirus causes an unusual reaction to the adenovirus. Alternatively, has the adenovirus itself recently changed to develop an easier-to-damage liver?


Severe hepatic impairment in children is very rare, says Helena Gutierrez, medical director of pediatric liver transplantation at UAB և Children’s of Alabama. But when that happens, most cases, even in normal times, remain completely mysterious. Almost no identical cause has been found half of the children with liver failure so severe that they may need a transplant. After all, understanding the latest pattern of unexplained cases of liver failure in children may shed light on previously mysterious cases that were once too rare to attract much attention.

But why the growth right now? The only culprits that can be definitively ruled out are the COVID vaccines, as children under 5, who make up the majority of hepatitis cases, still cannot be vaccinated. In the coming weeks, experts will review three key pieces of data to analyze the rest of the hypotheses.

The first և probably the most obvious data set to be collected is the following: Have these children had COVID-19 before? The vast majority of children with hepatitis have tested negative for coronavirus, but researchers are now collecting antibody data to find out if any of them have had COVID-19 before. “I do not think it is directly related to the virus,” Buchfelner said, “but perhaps COVID could have predisposed a child to liver failure when something else, such as an adenoviral infection, developed.” And though Multiple inflammatory syndrome or MIS-CAfter coronavirus infection can affect the liverPatients with hepatitis did not show the other feature signs of that conditionsuch as high inflammatory markers և heart damage.

When COVID antibody data appear, many children will be positive simply because many children, in general, have recently had COVID-19. Experts will want to go one step further to find out if coronavirus really plays a role. If so, they expect children with hepatitis to be more likely to have COVID antibodies than controls in children without hepatitis.

The second major data point is about adenovirus. Adenoviruses are very common, so can all positive tests simply detect accidental infections not related to liver failure? Here, too, investigators will want to see if children who are hospitalized with hepatitis are more likely to have a positive adenovirus test than those who are hospitalized for other reasons. If they are, the connection with the adenovirus becomes stronger. The UK is analyzing this exact data, and the results are expected next week.

Clearly how many children test positive for an adenovirus may seem like a simple statistic, but it can be confusing from the start when investigators are dealing primarily with retrospective data. Different doctors at different hospitals may think about ordering different tests. The UAB accidentally tested for adenovirus, but it’s so low on the list of hepatitis culprits that the test does not have to be routine. And how the tests are done can affect whether they are positive, says Benjamin Lee, a pediatric infectious disease doctor at the University of Vermont. “Is it possible to detect the virus in the blood when a patient seeks medical help?” Are there any other sites that need to be tested? ” he asks. What about the nose and throat? Or a stool? And indeed, British researchers have had to understand the fusion of blood, feces, and breath samples with varying degrees of positivity.

The third part of the investigation will focus on the adenoviruses found in these samples. The sequence of their genomes may determine whether viruses have recently acquired new mutations that may be linked to liver failure. Adenovirus variants have appeared in the past, and this type of virus is particularly suitable for altering its genome. The whole sequence of the genome is being worked out, as British scientists initially had difficulty extracting enough virus from early samples. And scientists do not have a large database of samples of such old adenoviruses to compare with new ones. “We think of it as SARS-CoV-2,” said James Platts-Mills, an infectious disease doctor at the University of Virginia. Thus, initial progress may be slow.

The partial sequence of the viral genome, however, has already identified one type of adenovirus that predominates in cases of hepatitis: adenovirus 41, also known as 41F. (There are more than 100 types of adenovirus. F: refers to species; The number reflects the sequence of species detection 🙂 Adenovirus 41 infects the gastrointestinal tract. Platts-Mills studied adenovirus in 41 developing countries where it is The main reason for hospitalization for diarrhea in children. It is also traded in rich countries, but in the United States it is not difficult enough to justify active control. Potentially, says Platts-Mills, hepatitis cases are just the tip of the iceberg for a large number of 41 undocumented mild adenovirus cases. The invisible growth, if any, may be due to either new viral mutations or the fact that very young children become infected at once with the relief of COVID restrictions.

However, it is strange to see adenovirus 41 especially as a suspect in these cases of hepatitis, the adenovirus experts told me. Whether the adenovirus is associated with severe liver failure is not an adenovirus 41 but a species. 1, 2, 3, 5 և 7:. In addition, these cases almost always occur in patients with suppressed immune systems. “You can see it in the liver of these immunocompromised children. “When we made the slides, you could see the virus particles,” said Kurt Scheberg, a UC Davis pathologist who studied. Adenoviral hepatitis. The dark centers of the infected liver cells become very swollen. All this is quite obvious. Biopsies did not reveal any of these patterns in the liver of non-immunocompromised children. If the adenovirus plays a role, it is probably more indirect. Probably a factor as to why they’re doing so poorly. And this can continue even after the virus is cleared, so adenovirus tests can be negative.

All this means that the answer to these cases of hepatitis in children will not be clear. “If we had found the virus in the liver, we would have ended it,” Buchfelner said in Alabama. “The fact that we can not find it means that it is much more difficult to prove.” Instead of one direct cause, investigators are probably looking for one or more indirect causes. Asking three key questions in the coming weeks, whether these children were also infected with COVID, whether their adenovirus infections were accidental, or whether their viruses were mutated would at least reduce the list of possible hypotheses.

At the same time, all nine children in Alabama are recovering. Whatever the reason, the doctors stressed to me that the risk of severe hepatitis in healthy children is still very, very small.

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