Introduction Chronic hepatitis B infection (CHB) has diverse disease phenotypes, ranging from minimal hepatic fibrosis, to cirrhosis and hepatocellular carcinoma (HCC)1. Serum viral markers are currently measured to inform clinical management, however none directly detect the covalently closed circular DNA (cccDNA) hepatocyte reservoir. Serum hepatitis B core related antigen (HBcrAg) has been correlated with cccDNA levels, and may predict HCC development2,3, but most studies are from Asia where genotypes B and C predominate4-6, so wider utility of HBcrAg is unknown. Serum Hepatitis B core-related antigen in a diverse UK cohort of patients with Chronic Hepatitis B infection Louise O Downs1,2, Tingyan Wang1,3, Marion Delphin4, Elizabeth Waddilove4, Monique Andersson2, Geoffrey Dusheiko5, Kosh Agarwal5, Eleanor Barnes1,2 Ivana Carey5, and Philippa C Matthews1,4,6,7 1 Nuffield Department of Medicine, University of Oxford, UK, 2 Department of Infectious Diseases and Microbiology, John Radcliffe Hospital, Oxford, UK, 3 NIHR Oxford Biomedical Research Centre, University of Oxford, UK, 4 The Francis Crick Institute, London, UK, 5 Institute of Liver Studies, King’s College Hospital, London, UK, 6 Division of Infection and Immunity, University College London, UK, 7 Department of Infectious Diseases, University College London Hospital, London, UK Contact Informations: Louise Downs: louise.downs@exeter.ox.ac.uk @lou_downs Philippa Matthews: philippa.matthews@crick.ac.uk @pippa_matt References 1 GBD 2019 Hepatitis B Collaborators, 2022 (PMID: 35738290) 2 Testoni et al, 2019 (PMID:30529504) 3 Carey et al, 2020 (PMID: 31701544) 4 Tada et al, 2018 (PMID: 28914957) 5 Tada et al, 2016 (PMID: 27034253) 6 Shimakawa et al, 2020 (PMID: 31102406) Aims We measured HBcrAg in a cross-sectional cohort of 143 ethnically diverse adults with CHB from a UK teaching hospital to understand how HBcrAg varies or is associated with: Patient demographics. Liver disease. Treatment Its use as a surrogate HBV DNA marker will also be investigated and whether this applies in all subgroups. Methods Clinical Metadata Patient data were collected in outpatient clinics and from Oxford University Hospitals Electronic Patient Records (EPR). 143 patients infected with HBV enrolled in the Oxford University Hospitals NHS Foundation with broad Viral Loads (VL). Participants provided written informed consent. Serum samples Liver Biomarkers (Alanine Transferase - ALT) HBV Biomarkers (HBeAg, HBsAg, VL) HBcrAg: chemiluminescent assay (Lumipulse G HBcrAg assay, Fujirebo) Statistical analysis was conducted in R (version 4.1.1) using the ‘ggplot2’ package (version 3.3.6). Correlations were all done using Pearson’s coefficient. Acknowledgments: Oxford University Hospitals laboratories NIHR Health Informatics Collaborative Kinga A Várnai and Oliver Freeman Results Figure 1: HBcrAg correlation with patients metadata HBcrAg was significantly correlated with HBsAg (A-B) and HBV DNA levels (D-E), however this was lost with HBeAg negativity (C,F). HBcrAg was still detected in those with undetectable HBV DNA. HBcrAg did not correlate with ethnicity (A), biological sex (B) or treatment (C) but is positively correlated with serum ALT (D) and decline significantly with age (E). 2 4 6 8 0 100 200 300 ALT (IU/L) HBcrAg (U/mL) 2 4 6 8 20 40 60 Age (years) HBcrAg (U/mL) E D 2 4 6 8 Arab Asian Black African Chinese European Other Asian Unknown HBcrAg (U/ml) A Ethnic group 2 4 6 8 Female Male HBcrAg (U/ml) B Biological Sex Figure 2: HBcrAg correlation with viral parameters in patients 4 6 8 0 2000 4000 HBsAg (IU/ml) HBeAg positive patients B 2 3 4 5 0 2000 4000 6000 HBeAg negative patients C A 2 4 6 8 0.0 2.5 5.0 7.5 HBcrAg (U/mL) All Patients D 4 6 8 0.0 2.5 5.0 7.5 HBV DNA (log IU/mL) HBeAg positive patients E 2 3 4 5 0 2 4 HBeAg negative patients F HBcrAg (U/mL) All Patients 2 4 6 8 No Yes HBcrAg (U/ml) Treatment status C 0.0 2.5 5.0 7.5 0 2000 4000 6000 R = - 0.19 p = 0.023 R = - 0.42 p = 0.047 R =