Cost-effectiveness of HES V2.0 and GALAD for hepatocellular carcinoma surveillance in patients with cirrhosis

Background: Ultrasound-based surveillance for HCC is limited by suboptimal sensitivity and low adherence. Blood-based biomarkers are potential alternatives for routine HCC surveillance. We aimed to define optimal sensitivity, specificity, and cost parameters under which blood-based biomarkers could serve as cost-effective alternatives in patients with cirrhosis. Methods: We developed a microsimulation model of the natural history of HCC in individuals with compensated cirrhosis. We compared the cost-effectiveness of biannual surveillance using 2 blood-based biomarkers—HES V2.0 and GALAD—versus ultrasound-based surveillance across a range of sensitivity, specificity, test costs, and adherence levels. Outcomes included quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs), with a willingness-to-pay threshold of $100,000/QALY. Results: At a $200 test cost, the optimal HES V2.0 performance was 83.8% sensitivity and 62.4% specificity, yielding more QALYs than ultrasound-based surveillance (6790 vs. 6780 per 1000 patients) with an ICER of $27,686/QALY. The optimal GALAD performance was 65.9% sensitivity and 76.4% specificity, yielding a modest QALY increase (6782 vs. 6780 per 1000 patients) with an ICER of $21,374/QALY. HES V2.0 detected more very early-stage HCCs than ultrasound-based surveillance (50.9 vs. 42.4 per 1000 patients) but increased downstream diagnostic imaging, whereas GALAD yielded smaller QALY gains with a moderate increase in diagnostic testing. At specificity ≥80%, neither biomarker was cost-effective, but cost-effectiveness was strongly influenced by adherence and test cost. Conclusions: Blood-based biomarkers such as HES V2.0 and GALAD can be cost-effective alternatives to ultrasound-based HCC surveillance under defined performance and cost conditions. These findings provide quantitative benchmarks to guide clinical evaluation and inform the development of future blood-based strategies for early HCC detection.