A multi-analyte cell-free DNA–based blood test for early detection of hepatocellular carcinoma
Mortality of liver cancer, with hepatocellular carcinoma (HCC) as the major histological type, has substantially increased over the past two to three decades in the United States and worldwide, and its incidence is projected to continue to increase over the next decade.[1–3] HCC prognosis remains dismal (5-year survival <15%) due to frequent diagnoses at late, noncurable stages.[4,5]
To increase HCC tumor detection at earlier stages that are more amenable to curative treatment, practice guidelines recommend semi-annual HCC surveillance using ultrasound with or without serum alpha-fetoprotein (AFP) for high-risk populations.[6–8] However, the suboptimal performance of current HCC surveillance tests hinders effective early tumor detection. The sensitivity of ultrasound for detecting early-stage HCC is only 45%, and a systematic review and meta-analysis study has suggested that the improvement to ultrasound by adding AFP is limited to only 63%. Additionally, the performance of ultrasound is reduced by various factors such as obesity, which is sharply increasing globally.[10,11] Thus, HCC surveillance tests with superior performance are urgently needed. In an effort to improve HCC detection, the GALAD score was developed by combining age, sex, AFP, Lens culinaris agglutinin-reactive AFP (AFP-L3%), and des-gamma-carboxy prothrombin (DCP). The GALAD score has shown superior HCC detection performance compared with AFP, but there is room for improvement,[13,14] indicating the still unmet need for HCC surveillance tests with substantially improved performance characteristics.