HBsAg Quantification‐Based Models for Predicting Hepatocellular Carcinoma Risk in Nucleos(t)ide Analogs‐Experienced Patients With Chronic Hepatitis B: The HBsAg ‐ HCC Score

BACKGROUND: Chronic hepatitis B (CHB) virus infection is the leading cause of hepatocellular carcinoma (HCC). Nucleos(t)ide analogs (NAs) effectively suppress HBV replication, but residual HCC risk remains in treated patients, highlighting the need for reliable risk stratification tools. Existing prediction models rely heavily on age and liver function parameters and often overlook hepatitis B surface antigen (HBsAg) quantification, a key marker closely tied to HBV-related HCC, resulting in inadequate clinical predictive accuracy. METHODS: To address this gap, we developed the novel HBsAg-HCC Score using a two-cohort design: retrospective training (1190 NA-treated CHB patients) with Cox regression to identify independent HCC risk factors, followed by validation in an independent prospective cohort (506 patients). Its performance was compared with three established tools (PAGE-B, mPAGE-B, aMAP). RESULTS: Five independent HCC risk factors were identified: higher HBsAg levels, older age, male sex, hypoproteinaemia, and elevated APRI. The HBsAg-HCC Score derived from these factors showed strong predictive power: 3-/5-/7-year AUCs of 0.867/0.872/0.871 in the training cohort (significantly outperforming PAGE-B, mPAGE-B, aMAP) and 0.784/0.780/0.777 in the validation cohort. Internal and external cross-validation confirmed its stability and reliability. CONCLUSIONS: By incorporating HBsAg quantification, a virus-specific marker often missing from conventional models, the HBsAg-HCC Score offers a more comprehensive and accurate approach to HCC risk stratification in NAs-experienced CHB patients, addressing a critical limitation of existing models directly.