OBJECTIVES: We set out to evaluate Hepatitis B core-related antigen (HBcrAg) as a proxy for hepatitis B (HBV) viral load (VL) and liver disease in two different population settings. METHODS: We undertook a cross-sectional retrospective observational study using samples and data from adults living with chronic HBV infection from the United Kingdom (UK, n=142) and South Africa (SA, n=211). We assessed HBcrAg distribution, relationship with other biomarkers, and risk stratification performance, applying point of care test (POCT) thresholds. RESULTS: SA and UK cohorts differed by ethnicity, HIV coinfection, HBeAg-positivity and proportion with HBV VL >200,000 IU/ml (all p<0.001). HBcrAg positively correlated with alanine aminotransferase (ALT) (in both settings p<0.01), and fibrosis/cirrhosis by APRI score (p=0.03 in UK, p=0.008 in SA), but not with elastography or FIB-4 scores. HBcrAg ≥4.3 log10U/ml (POCT threshold) was 100% sensitive and 92% specific for predicting VL >200,000 IU/ml in the UK cohort, compared to 94% sensitive and 86% specific in the SA population. CONCLUSIONS: HBcrAg correlated with VL, but less so with liver disease. Use of this biomarker needs tailoring for use in diverse populations.