Detection, Monitoring and Carcinogenesis Study of HBV-Related HCCs from Plasma cfDNA Fragmentation Profiles

Most of hepatocellular carcinoma (HCC) are associated with hepatitis B virus infection (HBV). Early detection of HCC can greatly improve prognosis but is not yet fully clinically implemented. This study aims to develop methods for detection and prognosis of HCC and to study the carcinogenesis of HBV using plasma cell-free DNA (cfDNA) whole-genome sequencing (WGS) data. Low coverage WGS was performed for 453 participants including healthy individuals, hepatitis B patients, cirrhosis patients, and HCC patients. Then the sequencing data was processed using various machine learning models based on cfDNA fragmentation profiles for cancer detection. Our best model achieved a sensitivity of 87.10% and a specificity of 88.37%, and it showed an increased sensitivity with higher BCLC stages of HCC. Overall, this study proves the potential of a non-invasive assay based on cfDNA fragmentation profiles for detection and prognosis of HCC, and reveals preliminary data on the carcinogenic mechanism of HBV.