Risk Prediction of Hepatocellular Carcinoma After Hepatitis B Surface Antigen Seroclearance in Patients With Chronic...

Prediction of hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) after hepatitis B surface antigen (HBsAg) seroclearance is important for optimizing surveillance strategies.

This study aimed to identify independent risk factors of HCC after HBsAg seroclearance and to develop and validate a risk prediction model.

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.

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.

The independent risk factors of HCC occurrence are age ≥ 50 years, male, platelet count≤ 150 × 10⁹/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.