Pediatric hepatitis - what do we know

Iss April 26, 2022 - What are the hypotheses about the origin of pediatric hepatitis in recent months?

At the moment none of the theories formulated on the origin has been confirmed by scientific evidence. In addition, every year in Italy, as in other countries, there is a certain number of hepatitis with unknown cause, and analyses are underway to determine whether there is actually an excess. The initial hypotheses of the investigation team in the UK proposed an infectious etiology or possible exposure to toxic substances. Detailed information collected through a questionnaire regarding the food, drink, and personal habits of the cases did not reveal common exposures. Toxicological investigations are ongoing, but an infectious etiology seems to be more likely based on the epidemiological and clinical picture.

Microbiologic investigations excluded hepatitis A, B, C, D, and E viruses in all cases. Based on these investigations, the current leading hypothesis is that a cofactor affecting young children having an adenovirus infection, which would be mild in normal circumstances, triggers a more severe infection or immune-mediated liver damage. Other aetiologies (e.g. other infectious or toxic agents) are still under investigation and have not been excluded but are considered less plausible. 

What is the trend, from the first cases to the present?

On April 5, 2022, the United Kingdom reported an increase in the number of cases of hepatitis in previously healthy children under age 10. On April 12, the UK reported that, in addition to the cases reported in Scotland, approximately 61 cases had been identified under investigation in England, Wales, and Northern Ireland, most between the ages of 2 and 5 years. On April 14, Scotland reported 13 cases under investigation including two pairs with epidemiologic links.

The clinical presentation of the cases in the United Kingdom was severe acute hepatitis with increased transaminases (AST/ALT) above 500 IU/L and in many cases jaundice. In the preceding weeks, some cases had presented with gastro-intestinal symptoms including abdominal pain, diarrhea, and vomiting. Most cases did not present with fever. Some cases received specialized care in pediatric hepatology units, and some cases received liver transplants.

As of 20 April 2022, 111 cases had been reported from the UK, and as of 27 April 2022 approximately 55 probable and confirmed cases have been reported from 12 EU/EEA countries. An additional 12 cases have been reported from the United States (US), 12 from Israel, and one from Japan. 

Is there a connection between hepatitis and the Sars-CoV-2 vaccine?

At the moment there are no elements that suggest a connection between the disease and vaccination, and indeed several considerations would lead to exclude it. 

• In almost all the cases in which the status is known, the affected children had not been vaccinated- the hypothesis that it is an adenovirus that causes hepatitis, put forward by some researchers, is in itself unlikely, since this type of virus is not normally associated with liver disease. 
• In any case, the adenovirus contained in vaccines with adenoviral vector against Sars-Cov-2 used in some countries (in Italy AstraZeneca and Janssen), is genetically modified so as not to replicate in the cells of our body. At the current state of knowledge, therefore, the phenomena of recombination between circulating adenovirus and vaccine strain do not seem biologically possible. These in fact presuppose the mixing of genes between viruses while they multiply, but this is not possible for the vector used for vaccination.

What does the Iss do?

At the moment there are several structures of the Iss that have been activated.

• SEIEVA. Network The Integrated Epidemiological System of Acute Viral Hepatitis (SEIEVA) is the special surveillance of acute hepatitis, active in ISS since 1985. SEIEVA supports and integrates the "Information System of Infectious and Diffusive Diseases", SIMID, managed by the Ministry of Health, in order to promote at local and national level the investigation and control of acute viral hepatitis.
• SARS-CoV-2 Genomic Surveillance. The Italian network is actively sharing data on the sequencing of SARS-CoV-2 strains of pediatric cases of acute hepatitis in which this infection has been confirmed. This will allow a better understanding of whether SARS-CoV-2 infection is an incidental event, due to the high circulation of the virus in Europe, or whether it should be considered the etiologic factor of these forms of hepatitis
• Event-Based Surveillance. With the Ministry of Health Circular No. 0047345 of October 19, 2021, event-based surveillance was formally established in Italy. The main actor for the implementation of event-based surveillance in Italy is the Italian Network of Epidemic Intelligence. Network referents have been activated following the alert since April 5, 2022.