For months, scientists around the world have been investigating cases of severe, unexplained hepatitis, or inflammation of the liver, in previously healthy children. According to the World Health Organization, at least 920 probable cases have been detected in 33 countries since October. About 5 percent require a liver transplant, and 18 deaths have been reported.
So far, explanations have remained elusive. A significant proportion of hepatitis cases in children have always been unexplained. There is still no consensus on whether such cases have become more common, and it is unclear whether the recently reported cases, which remain rare, are part of a new medical phenomenon or share an underlying cause. We do.
But a detailed investigation of the case has yielded clues.
Two new studies published Wednesday in the New England Journal of Medicine report that two medical centers — one in Birmingham, Ala., and the other in Birmingham, England — have recently seen an increase in the number of children with acute, unexplained hepatitis. . month.
The research also presents more circumstantial evidence that adenovirus 41, which often causes gastrointestinal symptoms, may be a contributing factor. In both studies, adenovirus infection was detected in about 90 percent of the children tested, and children who developed acute liver failure or required a transplant had higher average levels of the virus in their blood than those with mild cases. .
“I think adenovirus may be a player,” said Dr. Helena Gutierrez Sánchez, medical director of the Pediatric Liver Transplant Program at the University of Alabama at Birmingham and author of one of the new papers. “It seems to be a common sign, not only in our group but around the world.”
But the evidence is far from certain. And neither study found clear evidence that the virus was in the liver cells of any affected children, which suggested that if there was a link between adenovirus infection and hepatitis, it may not be straightforward.
“I don’t think it’s a subtle point,” said Dr. Saul Karpen, a pediatrician at Emory University and Children’s Healthcare of Atlanta, who wrote an editorial accompanying the two new papers. “I think that’s a key point.”
He noted that not all medical centers saw the same increase in cases, and a recent study by the Centers for Disease Control and Prevention did not find evidence that unexplained hepatitis had become more common in American children overall.
He said the new cases do not necessarily mean “something new and frightening”. “On the other hand, you can’t ignore it.”
Hepatitis has many causes, including certain medications and medical conditions, toxins, heavy alcohol use, and hepatitis A via the E virus.
Understanding Hepatitis
While inflammation of the liver is usually caused by a virus, hepatitis has many complicating factors, side effects, and stigma.
Adenoviruses, a family of viruses that usually cause cold- or flu-like symptoms, are not usually associated with inflammation of the liver in healthy children.
But physicians have detected adenovirus infection in several recent cases, including a group of children in Alabama, the first cluster of cases reported in the United States.
One of the new papers provides more information about cases of hepatitis in children at the Alabama Hospital in Birmingham. During the five-month period from October 2021 to February 2022, the hospital admitted nine children with acute, unexplained hepatitis, three times more than those admitted in the previous full year. “At least in our center, we had a spike,” Dr Gutierrez said.
Blood samples from eight of those nine children tested positive for adenovirus. Viral samples from five children yielded good genomic sequences that could be further analysed; All turned out to be adenovirus 41.
(During the same time period, the hospital also admitted six children who had a known cause of hepatitis. Of the five who tested for adenovirus, all were negative, and a review of laboratory records suggested that the infection was hospitalized. The overall patient population was not widespread in those days.)
In the UK, 44 children with acute, unexplained hepatitis were referred to the Birmingham Women’s and Children’s Pediatric Liver Transplant Center between 1 January and 11 April in 2022. Thirteen were admitted, with one to five patients being admitted over the same time frame. in past years.
Of the 30 children tested for adenovirus, 27 were positive. Britain’s Health Protection Agency later determined that the virus was adenovirus 41, said Birmingham Women and Children’s consultant pediatrician and study author Dr. Chayanani Kelgeri said.
The picture became more complicated when scientists analyzed liver samples from a group of affected children. Laboratory tests revealed no evidence of viral proteins or particles in the liver cells themselves.
(PCR testing found adenovirus DNA in liver samples from many children, but these samples may contain blood mixed with liver tissue, making it difficult to determine whether the genetic material came from the liver or blood, the scientists said. Told.)
“This leads us to question whether the virus was there, but what we are seeing in liver samples is the result of viral injury,” said Dr. Kelgeri.
Perhaps, she said, an adenovirus infection triggers an abnormal immune response in some children, and it is the immune response, rather than the virus, that damages the liver.
However, why some hospitals are seeing a rise in cases is unknown. If hepatitis has always been a rare consequence of adenovirus infection in children, cases may increase as the virus becomes more prevalent. The new cases of hepatitis in the UK coincide with “reports of increased adenoviruses” in the wider population, Dr. Calgary said.
Scientists said it is also possible that the virus may have changed or that other factors – such as previous exposure to COVID-19 – may have made some children more vulnerable to subsequent adenovirus infection. (Of those tested, 28 percent of British children tested positive for coronavirus, while 38 percent tested positive for coronavirus antibodies.)
Dr. Karpen said he was not yet convinced that there was a link between adenovirus infection and pediatric hepatitis – or that the incidence of both was increasing overall. Despite this, there is a need for more systematic data collection and analysis, he said.
“I am very happy that registries are being made so that we can know whether there is indeed a new virus in the city that needs attention,” Dr. Karpen said. “We really just need to gather information and keep our eyes open.”