Childhood hepatitis: a new hypothesis to explain the mysterious origin of the disease

This is the third epidemic under surveillance at the international level with that of Covid-19 and monkeypox. At last count, more than 1,000 children have contracted hepatitis whose origin still eludes scientists — they are new in France. Serious, the disease caused the death of about twenty of them and the hospitalization of several children, some of whom had to be transplanted liver.

If the track of the viral origin is the most serious to date, it remains to be seen which is at the origin of the symptoms liver disease presented by children. The possible role of SARS-CoV-2 and of theadenovirus type 41 is under investigation. An English research team, affiliated with the University of Glasgow, also offers its view on the question. In a pre-publication available at the server MedRxivshe is interested in another virus which causes very common respiratory infections, AAV2.

A new viral hypothesis

AAV2 is a small naked virus belonging to the genus Dependoparvovirusformerly called adenovirus-associated virus. It usually infects children in the same age group as those affected by the unknown hepatitis outbreak. Scientists have made PCR tests to detect the presence of AAV2 in a handful of children suffering from hepatitis: it was detected in the liver and plasma of young patients.

But to replicate, AAV2 needs the help of a virus. helper which co-infects the same cell as itself. This virus” helper most often belongs to the family of human adenoviruses (type C or F) or herpesviruses (HHV6B). These two viruses were also identified by PCR in some biopsies of liver performed on patients.

Faced with these observations, the researchers propose this hypothesis: We believe that AAV2 could be directly involved in the pathology non-AE hepatitis in children, following co-infection with HAdV (or HHV6B, although this is less likely) or as a consequence of reactivation [ndlr : de l’AAV2] by HAdV or HHV6B. This work will still have to be proofread by the scientific community before being published in a serious journal. Waiting for evidence solidthe mystery of the origin of pediatric hepatitis remains.

Pediatric hepatitis of unknown origin may be linked to SARS-CoV-2

Article published on May 22, 2022 by Julie Kern

As cases of pediatric hepatitis of unknown origin multiply, scientists rack their brains for an explanation. The viral track is preferred for the moment: adenovirus type 41 or coronavirus or both? Let’s take stock of current knowledge.

The hepatitis epidemic of as yet unknown origin affecting children throughout the world continues to spread. Since its detection in early April 2022, more than 450 children have contracted the disease and eleven died from it in Indonesia, the United States and Palestine. Several of them also had to undergo graft of liver.

This hepatitis poses a glue to scientists. Young patients are negative for hepatitis viruses from A to E which, as their name suggests, multiply in liver cells and cause damage there. The hypothesis favored today is that of an infection by another virus, adenovirus type 41. Nevertheless, the latter is not known to induce liver problems in children, with the exception of those who are immunocompromised.

SARS-CoV-2 involved?

In correspondence published in The Lancet Gastroenterology and HepatologyPetter Brodin, of theImperial College of London, and Moshe Arditi, of Cedar Sinai Hospital in Los Angeles, offer another line of thought that involves SARS-CoV-2, without setting aside type 41 adenovirus. We speculate that the recent cases of severe pediatric hepatitis could be the consequence of infection by an adenovirus with a tropism intestinal infection in children previously infected with SARS-CoV-2 and carriers of viral reservoir. »

Several observations support their hypothesis. About 12% of young patients identified in Europe were positive for SARS-CoV-2 at the time of admission to hospital. Tests are in progress to look for the presence ofantibody anti-SARS-CoV-2, a sign of a few months old infection. For the 19 European cases for which this information is available, 14 do indeed have anti-coronavirus antibodies. In addition, the majority of hepatitis cases concern children under 5 years old, who are ineligible for the vaccination.

Mechanisms still hypothetical

The two scientists propose to see if the stools of children contain the genome of SARS-CoV-2, which would be a sign of the persistence of the infection in the intestinal tract, but also to characterize the nature of the immune response which could reveal a “superantigen” type mechanism.

Viral superantigens are different from antigens classics. They not only activate the lymphocytes T which recognize them specifically, but all those which carry a receptor, the TCR, identical – whole families of cells are thus stimulated. Some scientists believe that a superantigen, possibly a piece of the protein S of the coronavirus, would be responsible for the severe form of Covid-19, a generalized inflammatory state which can affect the liver, in children.

What do we know about cases of hepatitis of unknown origin that have affected children for several months?

Article published on April 22, 2022 by Julie Kern

More than a hundred cases of hepatitis, originally still debated, concern children in the United States but also in Europe and France. Doctors have not yet formally identified their origin but a virus other than hepatitis is suspected.

At the beginning of April, WHO has received an unusual report ; ten children under the age of 10 contracted severe hepatitis — one inflammation liver — in Scotland. Today, UK health authorities identify a total of 108 similar cases. On the other side of the Atlantic, the CDC just released a note indicating that five cases of pediatric hepatitis have been identified in an Alabama hospital as of November 2021; and four more since. In Europe, Spain, Denmark, Ireland but also France, with two cases reported in Lyon, are concerned.

Atypical liverworts in children

Affected children have severe symptoms requiring hospitalization, including jaundiceof the diarrheavomiting and pains intense abdominals. Most of the children were able to be treated quickly, although a minority of them suffered a transplantation of liver. No deaths have been reported to date. Hepatitis is not common in children and the precise origin of these cases remains unknown although doctors have a lead: a virus.

Liver inflammations can be caused by viruses,alcoholand excess of certain medications or by underlying autoimmune diseases or genetic. The problem is that recent pediatric cases are negative for hepatitis viruses from A to E, the most common cause of liver inflammation. Doctors suspect another virus but which is not known to attack the liver.

Adenoviruses are viruses DNA double-stranded, large that are transmitted by contact with contaminated objects or respiratory droplets. This family includes about 50 different viruses, 40 of which can infect humans. In the majority of cases they cause respiratory infections but some types can also cause gastroenteritisof the cystitisconjunctivitis and in very rare cases, encephalitis. There is no specific treatment for adenovirus infection.

Adenovirus type 41 suspected culprit

Doctors are particularly interested in adenovirus type 41 which is known to cause gastroenteritis, often combined with respiratory damage, in children. Cases of hepatitis caused by adenovirus type 41 infection have been documented but only in immunocompromised children in healthy children, this virus is not known to cause such a symptom.

Sick children in the United States have all tested positive for adenovirus type 41, the remaining cases are under investigation. ” If an adenovirus is responsible, it could be a new variant that can cause liver damage in children whose immune system is naive. But we need to know more to be sure. On the other hand, if adenovirus is the culprit of hepatitis in healthy children, we need to look for other infections or environmental causes that could exacerbate the inflammation caused by adenovirus. “, explains Zania Stamataki, associate professor in viral immunology at the Center for Liver and Gastrointestinal Research from Birmingham.