A Multi-Analyte cfDNA-based Blood Test for Early Detection of Hepatocellular Carcinoma.

Abstract

Background & aims: Patients at high-risk for hepatocellular carcinoma (HCC) are recommended to undergo biannual abdominal ultrasound, which suffers from low sensitivity for small HCC nodules and poor adherence. To address these clinical needs, the multianalyte HelioLiver Dx blood test was developed to aid in the detection of HCC for patients at high risk for HCC due to cirrhosis.

Methods: The performance of the HelioLiver Dx test and ultrasound for the detection of HCC in adults with cirrhosis was evaluated in a cross-sectional, prospective, blinded, multicenter validation study. All participants provided blood specimens for the HelioLiver Dx test and underwent ultrasound. All participants also underwent multiphasic MRI as the gold standard to determine HCC status.

Results: Of 1,268 evaluable participants, 46 (3.6%) were considered to have HCC as determined by MRI, with many (46%) having small HCC lesions ≤ 2 cm in diameter. The HelioLiver Dx test had a sensitivity of 47.8% (95% CI, 32.9-63.1) for all HCC lesions and 28.6% (95% CI, 11.3-52.2) for HCC lesions ≤ 2 cm. In contrast, ultrasound demonstrated a lower sensitivity of 28.3% (95% CI, 16.0-43.5) for all HCC lesions and failed to detect any (0%; 95% CI, 0.0-16.1) HCC lesions ≤ 2 cm. The specificity of HelioLiver Dx and ultrasound were 87.6% (95%CI 85.6 to 89.4) and 93.9% (95%CI 92.5 to 95.2), respectively. The HelioLiver Dx test met prespecified co-primary endpoints for superior sensitivity and non-inferior specificity compared to ultrasound.

Conclusion: The HelioLiver Dx test identified more HCC lesions overall and more small lesions compared to other testing modalities. An accurate and convenient blood-based test may improve HCC detection through earlier detection and reduced patient barriers to testing.

Clinicaltrials: gov identifier: NCT03694600 IMPACT AND IMPLICATIONS: There is a significant, unmet clinical need for more sensitive and accessible methods for the early detection of hepatocellular carcinoma (HCC) in high-risk patient populations. The current study is the first blinded, multicenter, prospective study to evaluate the performance of a multianalyte blood test compared to abdominal ultrasound for the detection of HCC among patients with cirrhosis. The multianalyte HelioLiver Dx test met prespecified co-primary endpoints for superior sensitivity and non-inferior specificity compared to ultrasound for detection of HCC lesions. The availability of a more accessible, convenient and sensitive blood test to aid in the detection of HCC may improve utilization and consequently clinical outcomes for high-risk patients via reduction of care barriers and improved early HCC detection.