ABSTRACT Background Prediction of hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) after hepatitis B surface antigen (HBsAg) seroclearance is important for optimizing surveillance strategies. Aim This study aimed to identify independent risk factors of HCC after HBsAg seroclearance and to develop and validate a risk prediction model. Methods A total of 6536 CHB patients who achieved HBsAg seroclearance between January 2006 and June 2025 were retrospectively screened, with 3852 patients meeting the criteria for final analysis. A predictive model was developed via multivariate Cox proportional hazards regression analysis, with discrimination assessed using Harrell's C‐index and time‐dependent receiver operating characteristic curve area under the curve (AUC). Internal validation of the model was conducted through bootstrap resampling analysis. Results During 21,711 person‐years of follow‐up, 128 patients (3.3%) developed HCC (incidence rate: 0.59% per year). Multivariable analysis identified age, male sex, cirrhosis, antiviral therapy (AVT)‐induced seroclearance and lower levels of platelets and albumin as independent predictors of HCC. The six independent variables were used for constructing the novel prediction model. Harrell's C‐index of the model was 0.766. The novel model has a good predictive ability for HCC risk in the 3‐year (AUC = 0.785), 5‐year (AUC = 0.775) and 10‐year (AUC = 0.830) with similar discriminative performance observed in internal validation. Conclusions The independent risk factors of HCC occurrence are age ≥ 50 years, male, platelet count≤ 150 × 10 9 /L, albumin level ≤ 44 g/L, with cirrhosis at HBsAg seroclearance and AVT‐induced HBsAg seroclearance. Our six‐factor model enables risk stratification among patients achieving HBsAg seroclearance and may assist in informing surveillance strategies in clinical practice.
Ying et al. (Mon,) studied this question.