Temporal trends and clinical characteristics of acute hepatitis with unknown aetiology and human adenovirus infections in Oxfordshire from 2016 to 2022

ABSTRACT Background An outbreak of severe acute hepatitis of unknown aetiology (AS-Hep-UA) in children during 2022 has subsequently been linked to infections by adenovirus-associated virus 2 (AAV2) and other ‘helper viruses’, including human adenovirus (HAdV). Aim We investigated clinical characteristics and temporal distribution of acute hepatitis with unknown aetiology (AHUA) and of HAdV infections in Oxfordshire, UK population between 2016-2022. Methods We used anonymised electronic health records (EHR) to collate retrospective data for presentations of AHUA and/or HAdV infection between 2016-2022. We reviewed records of >900,000 acute presentations to emergency care at Oxford University Hospitals NHS Foundation Trust (OUH; UK) and performed a descriptive analysis of case numbers and clinical characteristics. Results Over the full study period, patients coded as AHUA 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. Comparing events within the outbreak period (1st Oct 2021 - 31 Aug 2022), to those occurring outside this period, significantly more adults were diagnosed with AHUA (p<0.0001, OR=3.01, 95% CI: 2.20-4.12), and there were significantly more HAdV infections in children (p<0.001, OR=1.78, 95% CI:1.27-2.47). There were also more HAdV tests administered during the outbreak (p<0.0001, OR=1.27, 95% CI:1.17-1.37). There was no evidence of more acute hepatitis or increased severity of illness among patients who tested HAdV-positive compared to those testing HAdV-negative. Conclusion Our results highlight an increase in the number of AHUA in adults coinciding with the reported AS-Hep-UA outbreak in children, but not linked to documented HAdV infection.