The search for the origin of severe childhood hepatitis continues, which has caused two deaths in Spain

The cause of the disease, however, is still unknown. Almost three months have passed since the concentration of cases in the United Kingdom gave rise to the alert launched by the World Health Organization, but hepatologists ask for margin and time to analyze the origin and call for caution. The latest data indicates that 506 cases of severe hepatitis of unknown origin have been detected in children under 16 years of age in a total of 21 countries. 53.9% in the United Kingdom. In Spain, there are 46.

“We need to carefully purge all the causes,” says Javier García-Samaniego, head of the hepatology section at the La Paz university hospital (Madrid). “There is still no conclusive study”, summarizes María Buti, head of the Hepatology and Internal Medicine service at the Vall D’Hebron hospital. The doctor assures that the investigations are still under way and that the deaths of the two minors are within what is expected.

The adenovirus hypothesis

Regarding the origin of the disease, which continues to be the puzzle for researchers, the hypothesis that gains more strength, also for the Ministry of Health, is that it is caused by adenoviruses, very common pathogens that in adults often go unnoticed and in children they are the most frequent cause of viral gastroenteritis. “Adenoviruses very frequently infect children. What is not frequent is that serious cases occur, ”says García-Samaniego.

Even so, researchers continue to work on detecting the origin of the disease. “We must try to delve into the causes because we know that it is a non-A and non-E hepatitis,” says García-Samaniego, who insists that “a significant percentage of cases have been linked to some type of adenovirus.” In our country, according to the latest Health data, they are 47.6% and globally, 54.5%.

The point is that this virus “in theory would not potentially cause” these conditions, Buti points out, so it is suspected that there are cofactors that may be unleashing them. The expert assures that one of the possibilities that “is gaining more and more strength” is that there is a co-infection of adenovirus with SARS-CoV-2 – the coronavirus that causes COVID-19 – behind it, although “not in all cases it has been identified this”, warns the doctor, who heads the Public Health and Political Relations Committee of the European Association for the Study of the Liver. Globally, the WHO estimates 11.3% of cases that tested positive for the virus.

Although there are several investigations underway, including some that do not rule out some “toxic exposure” as a possible cause, the European Center for Disease Prevention and Control (ECDC) points to an “infectious etiology” as the “most likely” origin.

For his part, Sami Aoufi Rabih, a specialist in the Digestive Service of the La Mancha Centro Hospital Complex and president of the Spanish Liver and Kidney Association, disassociates the coronavirus from this health alert. “Attempts have been made to link childhood hepatitis to SARS-CoV-2 and adenovirus, but current research has not shown this causality,” he says. For his part, the La Paz specialist considers that “until now, the presence of “some other cofactor” or the influence of the pandemic in these cases cannot be ruled out.

Also, remember that “the association with some herpes viruses has been reported.” In this line, Health emphasizes that in the investigations carried out by the National Center for Microbiology “seven positive cases for herpes virus have been detected.” Even so, this specialist asks for “caution” and recalls that there are several unknowns to be resolved about the origin of the infection.

Figures within the expected

In our country, Health considers that “the number of cases of hepatitis of unknown cause in children and transplants observed in this alert are within those expected according to estimates made with data from previous years”, although it also adds that the estimates ” They are not entirely conclusive. Buti points out that “in some places” increases have been detected. “It has always existed, but perhaps not grouped so close in time,” he analyzes

“It makes sense for health professionals to be on the alert, in case this or any other pathology constitutes a variation of normal,” says Aoufi Rabih. And he reviews: “At the moment, with the data from the WHO, all the countries except the United Kingdom present an incidence rate very similar to that of previous years.”

For the experts, it is key that the proportion of those who have required a transplant does remain stable compared to other years, as reported by Health. “One explanation could be that different factors are probably coming together and some more are added to the acute ones that were seen before,” Buti points out. According to the information broken down by the Ministry, in 2021 and 2020 eight minors required a liver transplant in Spain due to acute or subacute fulminant liver failure.

“The message that we have to send must be reassuring and not alarm, because it is in line with what was previously reported,” says the expert. In fact, it is not even clear if this is something new or has to do with a greater detection that was not previously carried out. García-Samaniego, the head of the hepatology section of the La Paz university hospital, states that the “health alert has worked” because the “coordination between autonomous communities and the Ministry’s CCAES” is evolving very favorably.

two deceased children

Of the 46 cases that have been registered in Spain, three of them required a liver transplant. This registry includes the two deceased minors and a third three-year-old girl from Aragon who currently presents “good clinical evolution”, according to the CCAES.

The six-year-old boy who died after the intervention began to have symptoms on July 2 and on the 18th of the same month he was transferred to a Madrid hospital for a “serious transplant” with “brain edema”, indicates Health. He underwent the operation on July 29 and died 24 hours after the intervention.

The 15-month-old baby lived in Andalusia. She was admitted at the end of June with a “box of acute gastroenteritis with a positive culture for adenovirus in a critical situation (encephalopathy and severe coagulopathy)”, notes the CCAES. “The case required an urgent liver transplant and died in the following 24 hours,” explains Sanidad.

Childhood hepatitis of unknown origin is present in several autonomous communities. Madrid registers the highest number of cases (15), but it has also been detected in Catalonia (9), Galicia (5), the Balearic Islands (4), Castilla-La Mancha and Murcia (3), Andalusia (2 and the deceased child of 15 months that Health breaks down as ‘additional case to the series presented’), Castilla y León (2) and Aragón and Canarias, both with one.

Early diagnosis and early referral

In Spain, 46 cases have been registered so far without an epidemiological link between them or a common cause, reports Health. The vast majority of those affected are less than ten years old, while the average age is 5.3. By sex, 29 cases were girls (64.4%) and 16 boys (35.6%), “observing a higher proportion of girls, especially in the group up to five years old.”

Among the cases for which information on symptoms is available, the most frequently reported were malaise, vomiting, fever and abdominal pain. In addition, half have jaundice (yellow skin) and some have diarrhea or respiratory symptoms. Among those affected, “early diagnosis and early referral to a reference center specialized in hepatology and, if necessary, in liver transplantation is essential,” says Aoufi Rabih.