Multi-target blood test for hepatocellular carcinoma early detection: A cross-sectional analysis of the prospective ALTUS study

Authors

• Binu V John
• Mark Camardo
• Amit G Singal
• Neehar D Parikh
• Ju Dong Yang
• Lewis R Roberts
• Alvin C Silva
• Naga Chalasani
• Reena Salgia, Henry Ford HealthFollow
• John B Kisiel
• Kyle Porter
• Paul Z Elias
• Elle Kielar-Grevstad
• Janelle J Bruinsma
• Marilyn C Olson
• Jorge Garces
• Paul J Limburg

Recommended Citation

John BV, Camardo M, Singal AG, Parikh ND, Yang JD, Roberts LR, Silva AC, Chalasani N, Salgia R, Kisiel JB, Porter K, Elias PZ, Kielar-Grevstad E, Bruinsma JJ, Olson MC, Garces J, Limburg PJ. Multi-Target Blood Test for Hepatocellular Carcinoma Early Detection: A Cross-Sectional Analysis of the Prospective ALTUS Study. J Hepatol. 2026.

Document Type

Article

Publication Date

9-26-2026

Publication Title

Journal of hepatology

Abstract

BACKGROUND & AIMS: Globally, 350 million people are at risk for HCC. Ultrasound screening is recommended but is limited by poor sensitivity for early-stage HCC 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 US, 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 CT or MRI as the 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 3,089 participants, 2,293 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 of 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 blood collection.

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.

IMPACT AND IMPLICATIONS: Hepatocellular carcinoma (HCC) screening remains limited by the suboptimal sensitivity of ultrasound, particularly among patients with obesity and steatotic liver disease. In this prospective multicenter study, a multi-target HCC blood test demonstrated substantially higher sensitivity for early-stage HCC detection than ultrasound while maintaining favorable screening performance across diverse patient subgroups. These findings are important for clinicians, researchers, and patients because they support further evaluation of blood-based approaches to address known limitations of imaging-based screening.

TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov (NCT05064553).

PubMed ID

42800682

ePublication

ePub ahead of print