Abstract / Summary
Earlier-onset hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) infection imposes a substantial clinical and societal burden. Hepatitis B core-related antigen (HBcrAg), a serum marker of intrahepatic covalently closed circular DNA activity, may capture persistent oncogenic viral activity, but its relationship with the age of HCC onset remains unclear. We retrospectively analyzed 43 patients with newly diagnosed HBV-related HCC and 207 HBV-infected patients without HCC at Shinshu University Hospital. Serum HBcrAg was measured using an ultrasensitive iTACT immunoassay. Among patients with HCC, those with earlier-onset disease (<65 years) had markedly higher HBcrAg levels than those with late-onset disease (4.90 vs 2.50 log U/mL, p < 0.001). HBcrAg remained independently associated with earlier-onset HCC after adjustment for HBsAg and HBeAg status (odds ratio 1.58, 95% CI 1.00–2.47, p = 0.048) and showed the highest discriminatory performance among evaluated biomarkers (AUROC 0.80). An HBcrAg threshold of 3.0 log U/mL identified earlier-onset HCC with 88.2% sensitivity and 69.2% specificity. In HBV-infected patients without HCC, HBcrAg levels declined with age and were substantially lower than in earlier-onset HCC. Elevated serum HBcrAg may characterize a distinct virological phenotype associated with younger age at HBV-related HCC diagnosis.