Baseline Alpha-Fetoprotein Elevation and the Risk of Hepatocellular Carcinoma in Chronic Hepatitis B: A Multicentre Cohort Study

Alpha-fetoprotein (AFP) level and its changes in chronic hepatitis B (CHB) may influence the risk of future hepatocellular carcinoma (HCC). This study aims to evaluate the HCC risk in CHB patients with no overt HCC but with elevated AFP level and to explore the prognostic role of longitudinal changes in AFP and liver-related laboratory values. This multicentre cohort study included 10,639 CHB patients without a history of HCC from seven medical facilities in South Korea. Patients with a baseline serum AFP test and no HCC diagnosis on imaging within 3 months were included. Patients were categorised into high-AFP (≥ 10 ng/mL) and normal-AFP (< 10 ng/mL) groups. The primary outcome was the incidence of HCC within 2 years, with secondary outcomes focused on longitudinal changes in AFP and liver-related laboratory values. Propensity score matching (PSM) and Cox proportional hazard models were used to assess HCC risk. After 1:4 PSM, 1278 high-AFP and 3731 normal-AFP patients were analysed. The high-AFP group had a significantly higher 2-year incidence of HCC (HR: 4.29; 95% CI: 3.31–5.57). AFP levels increased in patients who developed HCC in both groups (p < 0.01). Among the high-AFP group, patients who did not develop HCC had elevated baseline alanine aminotransferase levels (p < 0.01), which decreased during follow-up (p < 0.01) unlike those who developed HCC. In conclusion, baseline AFP elevation in CHB patients is associated with an increased risk of developing HCC within 2 years. Longitudinal monitoring of AFP and liver-related laboratory values can help in risk stratification.