The advance of a strange hepatitis in children: new cases in the United States, Great Britain and Israel

More and more countries have reported cases of rare hepatitis in children. In addition to cases reported in early April in the United States, cases were added in Spain, Denmark, the Netherlands and Ireland and the United Kingdom. The novelty is that the United Kingdom and the United States increased cases, as reported by The New York Times through the Centers for Disease Control and Prevention (CDC).

A group of severe cases of hepatitis in children in Alabama prompted CDC to issue a nationwide health alert Thursday, urging doctors and health officials to be vigilant and report any similar cases. Health authorities are investigating the possibility that an adenovirus may be responsible.

Hepatitis is an inflammation of the liver that has a wide range of causes. Viral infections, especially those caused by hepatitis A, B, and C viruses, can cause the condition. Excessive alcohol use, certain toxic chemicals, some medicines, and other medical conditions can also cause hepatitis.

Inflammation of the liver is a general immune response to infection or injury, a sign that the body is trying to fight a possible disease. Symptoms in children are usually some (but not all) of the following: dark urine, gray stools, yellowing of the skin and eyes (called jaundice), and high temperature.

The Alabama Department of Public Health has recorded 9 cases of hepatitis in healthy children under 10 years of age, which occurred between October and February. None of the children died, but several developed liver failure and two required liver transplants. All nine children tested positive for adenovirus infections. Several were found to have what is known as adenovirus type 41, which generally causes diarrhea, vomiting, and respiratory symptoms. North Carolina also identified two similar cases of severe hepatitis in school-age children, who have now recovered.

“It's not common for it to cause complete liver failure in healthy children,” said Dr. Aaron Milstone, a pediatric infectious disease specialist at Johns Hopkins Children's Center. “Right now, we think adenovirus may be the cause of these reported cases, but researchers are still learning more, including ruling out other possible causes and identifying other potential contributing factors,” the agency said.

Great Britain, for its part, has identified more than 100 cases in children under 10 years of age since January; eight have received liver transplants. Of the cases where adenovirus infections have been tested, more than 75 percent have tested positive, according to the UK Health Security Agency.

“The information gathered through our research increasingly suggests that this is related to adenovirus infection,” Dr. Meera Chand, the agency's director of clinical and emerging infections, said in a statement.

Israel's Ministry of Health said on Twitter this week that it was investigating 12 potential cases. Many questions remain about cases of hepatitis, which are still rare, experts emphasized.

“It's important not to panic,” said Dr. Richard Malley, an infectious disease doctor at Boston Children's Hospital. “But I think, for every reason you can imagine, it's important for CDC to ask doctors across the country to be vigilant.” Bertha Hidalgo, an epidemiologist at the Birmingham School of Public Health at the University of Alabama, agreed: “A group of cases, especially among this age group, is definitely something that needs to be closely monitored.”

Although it is possible that an adenovirus is the cause, the connection remains untested. Doctors noted that adenovirus infections are common in children and that children may have been infected with the virus incidentally. So far, there is no clear connection to the coronavirus that causes covid-19, experts said. Although several of the British children tested positive for coronavirus, none of the children in Alabama had Covid, according to the CDC

Dr. Milstone said he thought a connection to the coronavirus was “unlikely”, but that it could not be completely ruled out. “You have to put a question mark there,” he said.

The agency is asking health care providers to screen children with unexplained hepatitis for adenovirus infections and to report such cases to health officials.

The Coordination Centre for Health Alerts and Emergencies of Spain issued a report on Friday, April 22.

“On 5 April 2022, the National Focal Point of the International Health Regulations (IHR) of the United Kingdom (UK) reported to WHO 10 cases of severe acute hepatitis of unknown etiology in previously healthy children under 10 years of age in the Central Belt of Scotland. The ages ranged from 11 months to five years. Nine cases had an onset of symptoms during March 2022 and one had an earlier onset, in January 2022. Symptoms included jaundice, diarrhea, vomiting, and abdominal pain. All 10 cases were detected while they were hospitalized,” reads the statement.

“After launching a nationwide investigation, on 8 April 2022, a total of 74 cases meeting the case definition had been identified in the United Kingdom. The clinical syndrome in the identified cases is acute hepatitis with very high transaminases, often with jaundice, sometimes preceded by gastrointestinal symptoms, in children up to 10 years of age. Some cases required transfer to pediatric units specializing in liver, and six children required liver transplantation. According to reports, no children had died,” they added from the Spanish health portfolio.

“As of 20 April, the United Kingdom had recorded 108 confirmed cases: 79 in England, 14 in Scotland, 11 in Wales and 4 in Northern Ireland. The cases were not related to each other, 55% were girls between 0 and 10 years old (87% between 1 and 5 years old). In 8 of these cases, liver transplantation was necessary. None of them have died. In cases identified in the U.K., laboratory tests have excluded all hepatitis viruses (A, B, C, D, and E) in these children. One of the possible causes being investigated is that they are related to an adenovirus infection. In UK cases, 37 cases out of 48 analyzed (77%, 95% CI 62-87), were positive for adenovirus. In recent weeks, according to data provided by the surveillance of respiratory infections in the United Kingdom, the incidence of adenovirus infections has increased significantly compared to previous years,” they added in the report.

In Spain between January 1, 2022 and April 22, 2022, 13 cases of severe unaffiliated hepatitis were detected in people between 0 and 16 years of age: 8 cases that met the confirmed case criteria for initiation of research according to the UK definition, and 5 cases were classified as probable.

“The 8 confirmed cases (3 boys and 5 girls aged between 18 months and 7 years) started symptoms between 2 January and 24 March 2022 and have their residence in the Community of Madrid, Catalonia (2 of them), Galicia (2), Andalusia, Castilla-La Mancha and Aragon, are not related to each other, one has a history of trip to U.K. and. in one case a positive test was obtained for adenovirus. The evolution has been favorable, except in one case that required liver transplantation. Two of them could have another cause that would justify the clinical picture,” the report says.

They add: “The 5 probable cases (2 boys, 2 girls and 1 of unknown sex, aged between 12 and 16 years) and FIS between December 30, 2021 and April 1, 2022, have their residence in Catalonia (3), Andalusia (1) and Murcia (1).

In conclusion, the Spanish health portfolio report stated: “As a follow-up to the alert issued by the UK, in Spain, in coordination with all Autonomous Communities and with ISCIII, cases of severe acute hepatitis in children that have been occurring since January 2022 have been studied, but probably related to an increase in the incidence of adenovirus infection in the U.K. Epidemiology departments are applying a comprehensive questionnaire to all cases identified to date, without a common cause being found so far.”

They concluded: “It is being evaluated whether cases detected in Spain represent an unusual increase in cases of unaffiliated hepatitis compared to those detected in previous years or if they have different characteristics with cases that are usually identified. So far, and according to the first scans of data coded as unaffiliated acute hepatitis in children admitted to hospitals, the number of cases detected is lower than we would expect in the first 4 months of the year. The entire public health and healthcare system has been rapidly activated to provide a coordinated response to the need for information related to this alert launched by the U.K.

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