An abnormal reaction of the immune system that usually occurs in the presence of the AAV2 virus is the cause of acute hepatitis that has affected more than a thousand children in 35 countries since last spring and whose origin had until now been an enigma. This is the conclusion reached independently by three investigations carried out in the United Kingdom and the United States, the two most affected countries, which are presented today in the journal Nature.
The results show that the AAV2 virus is found in almost all affected children and only in a small percentage of healthy children or those with other forms of hepatitis. But AAV2 must be accompanied by infections by other viruses, and in many cases by a genetic predisposition, to trigger hepatitis.
The coincidence between the increase in childhood hepatitis cases with the end of the restrictions due to the pandemic, and their decrease in the following months, suggests that covid could have contributed to the phenomenon.
"New cases have stopped appearing for months," reports Maria Buti, a hepatologist at the Vall d'Hebron hospital in Barcelona.
The first cases were known in April last year when children under the age of five began to be admitted to hospitals in the United Kingdom. They had abnormally elevated transaminases, often with jaundice, sometimes with vomiting, and some progressed to acute liver failure. Of the 1,010 cases reported to the World Health Organization (WHO) as of July 8, 2022, 46 received a liver transplant and 22 died. In Spain, 40 cases were registered, one of which received a transplant.
The first hypothesis pointed to adenovirus 41 as the possible cause of these hepatitis after the presence of this pathogen was analyzed in affected children. But the hypothesis was not confirmed.
The three new investigations have carried out a metagenomic analysis, which consists of sequencing all the genetic material of a sample without assuming what pathogen can be found. In this way, viruses that are not suspected a priori can be identified.
In a first study led by the University of Glasgow, the AAV2 virus has been detected in 81% of affected children and in 7% of a control group of healthy children. The fact that there are control cases with AAV2 and without hepatitis shows that the virus is not enough to cause the disease.
Researchers have shown that 93% of sick children had a genetic variant that predisposes them to T cell-related autoimmune diseases. The presence of the AAV2 virus in altered liver cells surrounded by immune T cells indicates that the virus has a triggering role in acute hepatitis.
A second study led by University College London has detected high levels of AAV2 in 27 of the 28 cases it has analyzed (96%), but it has shown that hepatitis is not due to direct damage of the virus to the cells of the liver. liver. Researchers have detected two other viruses in the liver (adenovirus and human herpesvirus 6) in a large number of affected children and suggest that they may have contributed to hepatitis.
Finally, another study led by the University of California at San Francisco has detected AAV2 in 93% of cases analyzed (13 out of 14) and in 3.5% of control cases. As in the University College London study, California researchers have detected two other viruses in the liver of affected children (adenorivus plus human herpesvirus 6 or Epstein-Barr virus).
“The moment in which the hepatitis cases occurred in relation to the covid pandemic is striking,” Frank Tacke, a hepatologist at the Charité Berlin university hospital, who has not participated in these studies, points out in an analysis article in Nature. “It could be explained by the fact that children were suddenly exposed to a torrent of viruses after the restrictions, or had poorly trained immune systems, leading to increased vulnerability to normally harmless viruses.”
"We had always had sporadic cases of acute hepatitis of which we did not know the cause," says Maria Buti, from Vall d'Hebron. "From now on, when we have a new case of this type, we will be able to better study its cause, which can help us improve treatment."
