We designed an assay to profile multiple types of genetic variations in parallel so that 2 mL of plasma were sufficient to achieve high sensitivity in the detection of cfDNA mutations. The assay successfully identified four early-stage HCC cases (<3 cm) from 331 HBsAg (+) individuals who were negative based on screening with serum AFP and ultrasonography.

The positive predictive value was 17%, which was much higher than in previous studies. This paper shows that the combination of cfDNA and serum protein markers has significant promise for the early detection of HCC in the community population.