57 Hepatitis outbreak in children 3 Findings in context A study by Tan and colleagues17 used retrospective data from a single hospital in Oxfordshire (UK) and found an increase in the number of adults presenting with acute hepatitis of unknown aetiology (diagnosed using ICD-10 diagnostic codes or ALT values of at least 2x the ULN) at the time of the non A-E hepatitis outbreak in children, but found no increase in the number of HAdV infections in the same age group. Similar to our results in the UK, they found no evidence for an increase in elevated AST or ALT values in any age group. Another, questionnaire-based, study in 22 European countries using data from the first months of 2022 and comparing it to previous years, found no evidence for an increase in the occurrence of severe hepatitis in children18. A third study reported results that differ from our results. In England, the number of emergency department visits and hospital admissions were higher in 2022 compared to the years before for children (age 1-4 years) who presented with jaundice and liverrelated (non A-E) hepatitis illness. However, there was no data available from before the COVID-19 pandemic, and health-seeking behaviour may have changed during the pandemic15. We found differences in the rate of elevated AST and ALT tests in 3-week to 5-yearolds in geographically close locations. Similarly, an earlier study by van Beek and colleagues19 showed difference in the reported increase in cases of severe non A-E hepatitis in countries that are geographically close. The UK, Italy, Spain, Sweden, Ukraine and Israel reported an increase in the number of probable cases in the first months of 2022 compared to the preceding 5 years. No such increase was reported in Germany, the Netherlands or Denmark19. It is possible that more granular data on the location of the cases would show a different relationship between the rate of elevated AST and ALT measurements during the period in which cases were recorded, but due to Control of Patient Information regulations it was not possible to gather this data. Moreover, patients, especially children, may not always be admitted to the hospital nearest to them, but rather to a hospital that can provide specialised care, which also makes aggregation of the contributing locations more challenging. Interestingly, van Beek and colleagues19 found no increase in cases of severe non A-E hepatitis in the Netherlands and did find an increase in cases of severe non A-E hepatitis in the UK. There are several possible explanations for the difference with our results. First of all, they had data from one hospital in the Netherlands and five hospitals in the UK, while our study included data from nine Dutch hospitals and nine hospitals in the UK. The higher number of different locations increases the possibility of picking up a local signal. Second, their study was published early in the outbreak, and included data up to 18 April 2022, when cases were still being reported. In our study, the data extraction period ranged from March 2022 to December 2022. Finally, their cases involve patients between the age of 0 and 16, while our main analysis is focused on 3-week to 5-year-old children.
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