Characterisation of chronic hepatitis B virus infection in the UK and risk factors for hepatocellular carcinoma: a large electronic health record-based retrospective cohort study in the QResearch primary care database.

BackgroundWe set out to characterise chronic Hepatitis B (CHB) in the primary care population in England and investigate risk factors for progression to hepatocellular carcinoma (HCC). MethodsWe identified 8039 individuals with CHB in individuals aged [≥]18 years between 1999-2019 in the English primary care database QResearch. HCC risk factors were investigated using Cox proportional hazards modelling. FindingsMost of those living with CHB were males (60%) of non-White ethnicity (>70%), and a high proportion were in the most deprived Townsend deprivation quintile (44%). Among 7029 individuals with longitudinal data, 161 HCC cases occurred. Increased HCC hazards significantly associated with male sex (adjusted hazards ratio (aHR) 3.44, 95% Confidence Interval (95CI) 2.07-5.73), older age (for age groups 56-55 and [≥]66 years of age, compared to 26-35 years, aHRs 7.52 (95CI 4.14-13.67) and11.89 (95CI 6.26-22.60) respectively), socioeconomic deprivation (aHR for fifth Townsend deprivation quintile 1.69, 95CI 1.01-2.84, compared to third), Caribbean ethnicity (aHR 3.32, 95CI 1.43-7.71, compared to White ethnicity), ascites (aHR 1.85, 95CI 1.02-3.36), cirrhosis (aHR 6.52, 95CI 4.54-9.37) and peptic ulcer disease (aHR 2.20, 95CI 1.39-3.49). Reduced HCC hazards were associated with statin use (aHR 0.47, 95CI 0.22-0.99). InterpretationTargeting resources at vulnerable groups, and addressing modifiable risk factors is essential to improve CHB outcomes, and to support progress towards international goals for the elimination of hepatitis infection as a public health threat. FundingWellcome (grant ref 110110/Z/15/Z), UCLH NIHR Biomedical Research Centre, Nuffield Department of Medicine, University of Oxford, GlaxoSmithKline, NIHR Health Informatics Collaborative, Cancer Research UK. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSTHE CHB population in England has not been well described. Hepatitis B virus (HBV) reports from the UK Health Security Agency (UHKSA) have not previously reported chronic HBV (CHB) prevalence stratified by relevant subgroups, including ethnicity and socioeconomic status. The burdens of comorbid diseases in this population have also not been characterised. Furthermore, risk factors for the progression of CHB to hepatocellular carcinoma (HCC) have previously been identified largely in homogenous patient samples which may not be widely generalisable. Therefore, risk factors identified in previously published studies require validation in diverse multi-ethnic cohorts. Characterisation of CHB and investigation of novel risk factors for HCC is warranted in a large data source which contains parameters for a large percentage of the population which are collected in a systematic and wide-scale manner in order to improve generalisation of findings. Added value of this studyWe have characterised the largest cohort of CHB individuals in the UK to date, using the QResearch primary care electronic health record database, and describing the demographics and burdens of comorbid disease in the population. This is novel and has not previously been done in a large socioeconomically and ethnically diverse patient sample. We have also analysed risk factors for HCC in the cohort, both validating previously reported factors and investigating novel factors. Implications of all the available evidenceThe findings of this study have important implications for CHB prevention, clinical management, and resource planning. Our detailed description of the demographics and disease profile of the CHB population in the UK may facilitate the targeting of health and prevention resources. Findings concerning HCC risk factors have implications for the clinical management of CHB in order to reduce the risk of progression to HCC.