Studies Probe Adenovirus Link to Childhood Hepatitis Cases

For months, scientists around the world have been investigating cases of unexplained severe hepatitis or liver inflammation in previously healthy children.at least 920 possible cases detected In 33 countries since October, according to the World Health Organization. About 5% need a liver transplant and 18 people are reported to have died.

So far, the explanation remains elusive. A significant proportion of hepatitis cases in children are not always explained. There is still no consensus as to whether such cases have become more common, and whether recently reported cases, which remain rare, are part of a new medical phenomenon or share a root cause. Is not clear.

However, more detailed case studies are beginning to provide clues.

Two new studies published in the New England Journal of Medicine on Wednesday show two medical centers — One is in Birmingham, Alabama. When The other is in Birmingham, England — In recent months, the number of children with unexplained acute hepatitis has increased.

This study also provides more contextual evidence that adenovirus 41, which often causes gastrointestinal symptoms, may contribute. In both studies, adenovirus infection was detected in about 90% of children tested, and children with acute liver failure or in need of transplant had higher average levels of virus in their blood than children with mild illness. rice field.

“I think adenovirus could be a player,” said Dr. Helena Gutierrez Sanchez, medical director and author of a new paper on a pediatric liver transplant program at the University of Alabama at Birmingham. “It seems to be a common signal not only in our cohort, but around the world.”

But the evidence is far from definitive. Also, neither study found clear evidence that the virus was in the hepatocytes of the affected child. This suggests that if there is a link between adenovirus infection and hepatitis, it may not be simple.

“I don’t think it’s a subtlety,” said Dr. Sole Carpen, a pediatric hepatologist at Emory University and Atlanta’s Pediatric Medicine. editorial It was accompanied by two new treatises. “I think that’s the point.”

Not all medical centers have seen the same increase in cases, and recent studies at the Centers for Disease Control and Prevention find no evidence that unexplained hepatitis is becoming more common in all American children. It was.

He said that new incidents do not always represent “something new and scary.” “On the other side, it cannot be ignored.”

Hepatitis can have a variety of causes, including specific medications and medical conditions, toxins, heavy alcohol intake, and hepatitis A to E viruses.

Adenovirus is a family of viruses that usually cause symptoms like the common cold and flu, but is usually not associated with inflammation of the liver in healthy children.

However, clinicians have detected adenovirus infections in many recent cases, including a group of children in Alabama, the first group of cases reported in the United States.

One of the new treatises provides details on cases of hepatitis at the Children’s of Alabama Hospital in Birmingham. During the five months from October 2021 to February 2022, the hospital admitted nine children with unexplained acute hepatitis. This is three times the number of the previous year. “At least in our center, it has skyrocketed,” said Dr. Gutierrez.

Blood samples from 8 of those 9 children were tested positive for adenovirus. Virus samples from five children provided sufficient genomic sequences for further analysis. All turned out to be adenovirus 41.

(During the same period, the hospital also admitted six children with a known cause of hepatitis. Of the five tested for adenovirus, all were negative, and a review of the test records showed that the infection was in the hospital. It was suggested that it did not spread to the entire patient population at that time.)

In the United Kingdom, between January 1st and April 11th, 2022, 44 children with unexplained acute hepatitis were referred to the Birmingham Women and Children’s Pediatric Liver Transplant Center. The past few years.

Of the 30 children tested for adenovirus, 27 were positive. The UK Health and Safety Agency later determined that the virus was adenovirus 41, said Dr. Chayalani Kergeri, a pediatric hepatologist and study author at Birmingham Women’s and Children’s.

The picture became more complex when scientists analyzed liver samples from a subset of the affected children. Laboratory tests found no evidence that the hepatocytes themselves contained viral proteins or particles.

(PCR testing detected adenoviral DNA in liver samples from several children, but these samples may contain blood mixed with liver tissue, and the genetic material is in the liver. Scientists say it’s difficult to tell if it’s derived from blood or blood.)

“It casts doubt on us if the virus was there, but what we see in liver samples is the aftermath of virus damage,” said Dr. Kergeri.

Perhaps adenovirus infection causes an abnormal immune response in some children, and it is the immune response that damages the liver, not the virus, she said.

However, it is unclear why the number of cases is increasing in some hospitals. If hepatitis has always been a rare result of adenovirus infection in children, the number of cases may increase as the virus becomes more prevalent. New cases of hepatitis in the UK were consistent with “reports of increased adenovirus” in a wider population, Dr. Kergeri said.

According to scientists, some children may be more vulnerable to subsequent adenovirus infections due to changes in the virus or other factors, such as previous Covid-19 attacks. (Of the children tested, 28% of UK children were positive for coronavirus and 38% were positive for coronavirus antibody.)

Dr. Carpen said he was not yet convinced that there was a link between adenovirus infection and childhood hepatitis, or that the overall incidence of either was increased. Anyway, he said, more systematic data collection and analysis is needed.

“I’m very pleased that the registry has been created to find out if there really is a new virus in town that needs attention,” Dr. Carpen said. “We really need to keep collecting information and keep our eyes open.”