Risk-based hepatocellular carcinoma surveillance thresholds using a prediction score in Asian patients with chronic hepatitis B: a nationwide cohort study.

Background/Aims: This study aimed to quantify hepatocellular carcinoma (HCC) incidence according to a validated prediction score and to define score-based cut-offs corresponding to surveillance-relevant incidence thresholds in Asian patients with chronic hepatitis B (CHB) receiving antiviral therapy. Methods: We conducted a nationwide population-based cohort study using the Korean National Health Insurance Service database. Adults with CHB initiating nucleos(t)ide analogue therapy between 2012 and 2023 were included; those with viral coinfections, prior malignancy, or decompensated cirrhosis were excluded. HCC risk was stratified using the HCC-RESCUE score. Incident HCC was the primary outcome. Annual HCC incidence rates and adjusted hazard ratios were estimated using multivariable Cox proportional hazards models. Results: Among 199,143 treated patients (median follow-up, 7.3 years), 15,233 developed HCC. Adjusted annual HCC incidence increased progressively across risk strata: 0.31% (95% confidence interval [CI], 0.24-0.40) in the low-risk group, 1.09% (95% CI, 0.84-1.41) in the intermediate-risk group, and 1.85% (95% CI, 1.44-2.40) in the high-risk group. Compared with the low-risk group, adjusted hazard ratios for HCC were 3.48 (95% CI, 3.35-3.61) and 5.90 (95% CI, 5.62-6.19) in the intermediate- and high-risk groups, respectively (all P<0.001). HCC-RESCUE scores corresponding to annual HCC incidence thresholds of 0.2%, 1.5%, and 3.0% were 47, 66, and 90. Conclusions: In a large antiviral-treated Asian CHB population, prediction score-based stratification revealed a graded spectrum of residual HCC risk and identified incidence-aligned thresholds relevant to surveillance. These findings support incidence-informed refinement of HCC surveillance strategies that complement traditional cirrhosis-based criteria in the antiviral treatment era.