# Retrospective analysis of hospital electronic health records reveals unseen cases of acute hepatitis with unknown aetiology in adults in Oxfordshire

**Authors:** Cedric C. S. Tan, Gavin Kelly, Jack Cregan, Joseph D. Wilson, Tim James, Meera Chand, Susan Hopkins, Maaike Swets, J. Kenneth Baillie, Katie Jeffery, Ann Sarah Walker, David W. Eyre, Nicole Stoesser, Philippa C. Matthews

PMC · DOI: 10.1186/s12889-024-19292-1 · 2024-07-15

## TL;DR

A study using hospital records found a rise in unexplained acute hepatitis in adults during a child outbreak period, but no direct link to adenovirus.

## Contribution

The study reveals an increase in adult cases of acute hepatitis with unknown causes during a known child outbreak period, using electronic health records for surveillance.

## Key findings

- AHUA cases in adults increased significantly during the outbreak period.
- More adenovirus tests were performed during the outbreak, but no link to increased hepatitis severity was found.
- EHR data can detect population-level health trends and support outbreak surveillance.

## Abstract

An outbreak of acute severe hepatitis of unknown aetiology (AS-Hep-UA) in children during 2022 was subsequently linked to infections with adenovirus-associated virus 2 and other ‘helper viruses’, including human adenovirus. It is possible that evidence of such an outbreak could be identified at a population level based on routine data captured by electronic health records (EHR).

We used anonymised EHR to collate retrospective data for all emergency presentations to Oxford University Hospitals NHS Foundation Trust in the UK, between 2016–2022, for all ages from 18 months and older. We investigated clinical characteristics and temporal distribution of presentations of acute hepatitis and of adenovirus infections based on laboratory data and clinical coding. We relaxed the stringent case definition adopted during the AS-Hep-UA to identify all cases of acute hepatitis with unknown aetiology (termed AHUA). We compared events within the outbreak period (defined as 1st Oct 2021—31 Aug 2022) to the rest of our study period.

Over the study period, there were 903,433 acute presentations overall, of which 391 (0.04%) were classified as AHUA. AHUA episodes had significantly higher critical care admission rates (p < 0.0001, OR = 41.7, 95% CI:26.3–65.0) and longer inpatient admissions (p < 0.0001) compared with the rest of the patient population. During the outbreak period, significantly more adults (≥ 16 years) were diagnosed with AHUA (p < 0.0001, OR = 3.01, 95% CI: 2.20–4.12), and there were significantly more human adenovirus (HadV) infections in children (p < 0.001, OR = 1.78, 95% CI:1.27–2.47). There were also more HAdV tests performed during the outbreak (p < 0.0001, OR = 1.27, 95% CI:1.17–1.37). Among 3,707 individuals who were tested for HAdV, 179 (4.8%) were positive. However, there was no evidence of more acute hepatitis or increased severity of illness in HadV-positive compared to negative cases.

Our results highlight an increase in AHUA in adults coinciding with the period of the outbreak in children, but not linked to documented HAdV infection. Tracking changes in routinely collected clinical data through EHR could be used to support outbreak surveillance.

The online version contains supplementary material available at 10.1186/s12889-024-19292-1.

## Linked entities

- **Diseases:** acute hepatitis (MONDO:0002251)

## Full-text entities

- **Diseases:** acute severe hepatitis of unknown (MESH:D045169), infections (MESH:D007239), adenovirus infections (MESH:D000257), acute hepatitis (MESH:D017114)
- **Species:** Human adenovirus sp. (species) [taxon 1907210], Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11251388/full.md

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Source: https://tomesphere.com/paper/PMC11251388