Produced on 25 November 2022 at 10:45
Based on consistently stable trends and low incidence of hepatitis of unknown origin, ECDC in conjunction with the WHO Regional Office for Europe decided to stop the routine reporting of cases to TESSy at the end of 2022. There will be no further updates to the surveillance bulletin.
Surveillance summary
This report provides an overview of the cases of hepatitis of unknown origin in children aged 16 years and below reported to ECDC and the WHO Regional Office for Europe through The European Surveillance System (TESSy) hosted at ECDC.
As of 24 November 2022, 572 cases of acute hepatitis of unknown aetiology have been reported by 22 countries: (Austria (six), Belgium (14), Bulgaria (three), Cyprus (two), Denmark (eight), Finland (one), France (10), Greece (21), Ireland (29), Israel (five), Italy (50), Latvia (one), Luxembourg (one), the Netherlands (16), Norway (six), Poland (23), Portugal (28), Republic of Moldova (one), Serbia (one), Spain (54), Sweden (12), and the United Kingdom (280)).
Since the last surveillance bulletin, which used data as of 27 October 2022, 10 new cases have been reported from five countries (Bulgaria (two), Greece (two), Italy (three), Poland (one), and Portugal (two)). One case (Greece) previously reported was not included in the latest data update.
The epicurve shows cases by date of onset when available (396 cases), and date of hospitalisation (154 cases), or date used for statistics when the former two are not available (22 cases). The number of cases reported increased sharply starting in week 12 and remained stable between 29 and 39 cases per week up to and including week 18. Whilst reporting delay may influence case numbers in recent weeks, there has been a steady decrease in the number of cases reported weekly since week 17.
The majority (75.5%) of cases are five years old or younger.
Of the 572 probable cases, 405 have information available on clinical outcome. There have been seven deaths associated with the disease in the European Region.
Of 371 cases with available information, 100 (27%) required admission to an intensive care unit. Of the 320 cases for which this information is available, 24 (7.5%) have received a liver transplant.
Overall, 457 cases were tested for adenovirus by any specimen type and had a valid positive or negative result. Of these, 236 (51.6%) tested positive. The positivity rate was the highest in whole blood specimens (49.3%). Typing data are only available for 12 cases: type 31 (n = 1), type 40 (n = 4), type 41 (n = 5), and type other (n = 2).
Of the 392 cases PCR tested for SARS-CoV-2, 40 (10.2%) were positive. Serology results for SARS-CoV-2 are only available for 115 cases, of which 73 (63.5%) were positive. Of the 167 cases with data on COVID-19 vaccination, 148 (88.6%) were unvaccinated.
Introduction
Purpose and scope
This report provides an overview of the cases of hepatitis of unknown origin in children aged 16 years and below reported to ECDC and the WHO Regional Office for Europe for the period up to 24 November 2022, through The European Surveillance System (TESSy). Figures and tables describe national case-based data for surveillance of hepatitis of unknown origin in children aged 16 years and below from all the countries and areas of the WHO European Region, including the 27 countries of the European Union (EU) and the additional three countries of the European Economic Area (EEA).
Since the first alert launched by the UK on 5 April 2022, cases of hepatitis of unknown aetiology in children have been reported from multiple countries worldwide. It is not yet clear whether all cases identified following the alert are part of a true increase compared to the baseline rate of hepatitis of unknown aetiology in children.
The aetiology and pathogenetic mechanisms of disease are still under investigation. A possible association with current adenovirus infection has been identified, but other hypotheses and possible co-factors are under investigation. Most cases continue to be reported as sporadic, unrelated cases.
Data are submitted through the case-based record type NOVHEP to The European Surveillance System (TESSy) database hosted at ECDC.
Case definition
Cases of hepatitis of unknown origin should be reported to TESSy if they meet any of the following criteria:
- Probable: A person presenting with an acute hepatitis (non-hepatitis viruses A, B, C, D and E*) with aspartate transaminase (AST) or alanine transaminase (ALT) over 500 IU/L, who is 16 years old or younger, since 1 October 2021.
- Epi-linked: A person presenting with an acute hepatitis (non-hepatitis viruses A, B, C, D and E*) of any age who is a close contact of a probable case since 1 October 2021.
- Discarded: A subject previously classified as case, that following further investigations did not meet the case definition criteria.
*Cases of hepatitis with known aetiology such those due to specific infectious diseases, drug toxicity, metabolic hereditary, or autoimmune disorders should not be reported under this protocol.
Note that the UK local case definition includes only cases younger than 16 years which means cases aged 16 years are not reported to TESSy from the UK.
Key indicators
Epicurve
Overall
Number of cases per week by date of onset of illness or date of hospitalisation
(*) Week of onset of first symptoms of disease when available; if unavailable, week of hospitalisation (first) or week of notification to the national level (second).
Information on date of onset of illness was available for 396 cases. For those where this information was missing we used date of hospitalisation (154 cases) or ‘Date used for statistics’ which is a date variable defined by the country (22 cases). While ECDC does not have information on how this date is defined it may for example correspond to date of reporting to the national authorities.
By Country
Number of cases per week by date of onset of illness or date of hospitalisation, and reporting country
(*) Week of onset of first symptoms of disease when available; if unavailable, week of hospitalisation (first) or week of notification to the national level (second).
By Country (grid)
(*) Week of onset of first symptoms of disease when available; if unavailable, week of hospitalisation (first) or week of notification to the national level (second).
By Area
(*) Week of onset of first symptoms of disease when available; if unavailable, week of hospitalisation (first) or week of notification to the national level (second).
Summary table
Summary table by reporting country
Demography
Sex
Number of cases by sex
Age
Number of cases by age in years
Place of residence
Number of cases by place of residence (*)
(*) Reporting country if unknown or missing place of residence.
Adenovirus
Testing
Adenovirus test positivity (*) by specimen type
(*) Positivity calculated using specimens for which the result is known.
Note: 457 children were tested for adenovirus by at least one sample type. Of these, 236 (51.6%) were positive.
Summary table
Typing
Adenovirus typing
SARS-CoV-2
Testing
SARS-CoV-2 testing (*)
(*) Positivity calculated using specimens for which the result is known.
SARS-CoV-2 PCR: Result of SARS-CoV-2 PCR taken after onset of hepatitis
SARS-CoV-2 serology: Result of SARS-CoV-2 serology during this episode of hepatitis (Positive = Positive unspecified/IgG/IgM detected).
Of the 73 children with a positive SARS-CoV-2 serology result, 21 (28.8%) had a positive result for adenovirus by any sample, and 48 (65.8%) also had a positive result for any other pathogen.
Vaccination
SARS-CoV-2 current vaccination status
Other microbiological analysis
Result of testing for another pathogens
Legal notice and disclaimer
General Disclaimers
ECDC’s legal notice and disclaimer can be found at https://www.ecdc.europa.eu/en/legal-notice
Users are advised to interpret all data with caution and be aware of their limitations. Case counts and their corresponding data may have weekly updates that include historical corrections as new information is collected and reported.
The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of WHO or ECDC concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.
The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by WHO or ECDC in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.
All reasonable precautions have been taken by WHO and ECDC to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall WHO or ECDC be liable for damages arising from its use.
Copyright, permissions, and referencing:
The WHO Regional Office for Europe is responsible for the accuracy of the Russian translation.
Suggested citation: European Centre for Disease Prevention and Control/WHO Regional Office for Europe. Hepatitis of Unknown Aetiology in Children, Joint Epidemiological overview, 25 November, 2022.
Tables and figures should be referenced: European Centre for Disease Prevention and Control/WHO Regional Office for Europe. Hepatitis of Unknown Aetiology in Children, Joint Epidemiological overview, 25 November, 2022.
© World Health Organization 2022.
© European Centre for Disease Prevention and Control 2022.
Reproduction is authorized, provided the source is acknowledged.
Acknowledgements
We gratefully acknowledge the input of national public health staff involved in surveillance activities and data submission to TESSy.