Hepatocellular carcinoma development after hepatitis B surface antigen seroclearance in chronic hepatitis B patients: a 10-year single-center cohort study

BACKGROUND: Hepatitis B surface antigen (HBsAg) seroclearance is considered a functional cure in chronic hepatitis B (CHB), yet the risk of hepatocellular carcinoma (HCC) may persist. This study aimed to evaluate HCC incidence and identify risk factors after HBsAg seroclearance. METHODS: This retrospective single-center cohort included 259 CHB patients who achieved HBsAg seroclearance between 2013 and 2023. Patients with pre-existing HCC were excluded. During follow-up, 22 patients developed HCC. Clinical, demographic, and laboratory variables were analyzed. Independent risk factors were determined using multivariate logistic regression. RESULTS: HCC developed in 22 (8.49%) patients after seroclearance. In multivariate logistic analysis, a higher cirrhosis, age, male sex, platalet count, and hepatitis B score and shorter HBV infection duration were independently associated with HCC development after HBsAg seroclearance ( P < 0.005). Male sex and older age were significant in univariate analysis but not in multivariate analysis. Markers of liver dysfunction and fibrosis were significantly worse in patients who developed HCC. CONCLUSION: HBsAg seroclearance reduces but does not eliminate the risk of HCC. Patients with advanced liver disease and high-risk profiles remain vulnerable, underscoring the need for continued, risk-adapted HCC surveillance after seroclearance.