Background & aims: Globally, 350 million people are at risk for HCC. Ultrasound screening is recommended but is limited by poor early-stage sensitivity and low adherence. This study evaluated whether the multi-target HCC blood test (mt-HBT) demonstrates non-inferior sensitivity for early-stage HCC compared with ultrasound and assessed its specificity.
Methods: This prospective, multicenter study, conducted between July 2021 and June 2025 in the United States, evaluated the performance of the mt-HBT in a head-to-head comparison with standard-of-care ultrasound among adults with cirrhosis or chronic HBV infection who were eligible for routine HCC screening. All participants underwent computed tomography or magnetic resonance imaging as a reference standard. The co-primary outcomes were non-inferiority of mt-HBT to ultrasound for early-stage HCC sensitivity, with sequential testing of superiority, and mt-HBT specificity. A secondary outcome was overall (any-stage) mt-HBT sensitivity.
Results: Of 3089 participants, 2293 were evaluable with paired ultrasound and mt-HBT results. Thirty-seven HCCs were identified, with 27 classified as early stage by Milan criteria. Early-stage HCC sensitivities were 66.7% (95% CI, 47.8-81.4%) for mt-HBT and 22.2% (95% CI, 10.6-40.8%) for ultrasound, confirming mt-HBT non-inferiority within the prespecified 5% margin. The specificity for mt-HBT was 81.8% (95% CI, 80.1-83.4%), which did not meet the pre-specified co-primary outcome of 82%. Ultrasound specificity was 98.6% (95% CI, 98.0-99.0%). Any-stage HCC sensitivity was 73.0% (95% CI, 57.0-84.6%) for mt-HBT and 29.7% (95% CI, 17.5-45.8%) for ultrasound. No serious adverse events occurred during the blood collection process.
Conclusions: The mt-HBT had higher observed sensitivity than ultrasound for early-stage HCC, with a paired absolute difference of 44.4% (95% CI, 20.2-63.8); however, specificity did not meet the prespecified target.
https://www.journal-of-hepatology.eu/article/S0168-8278(26)02904-1/abstract
