Hepatitis B virus (HBV) infection is a significant risk factor for hepatocellular carcinoma (HCC). During the infection, HBV DNA integrates into the host genome, promoting hepatocarcinogenesis through both gene-dependent and gene-independent mechanisms. It can activate oncogenic gene transcription or produce chimeric and novel proteins that contribute to tumorigenesis. On the other hand, it also compromises genomic stability on a large scale. Furthermore, HBV integration can alter the liver microenvironment, fostering conditions conducive to tumor development. HCC remains one of the most challenging cancers to treat, primarily due to the incomplete understanding of HCC, inadequate diagnostic and prognostic strategies, and limited effective therapeutic options. Liquid biopsy represents a significant advancement in oncology, offering a non-invasive tool for cancer detection and management. HBV integration detection through liquid biopsy serves as a promising strategy for managing HBV-associated HCC. Importantly, it exhibits preferential patterns that differentiate HCC from chronic hepatitis or cirrhosis patients, making it a potential biomarker for HCC diagnosis. Moreover, the quantification of HBV-host chimeric reads in the bloodstream can indicate the presence of residual tumor cells post-surgery, serving as a promising biomarker for the screening of HCC recurrence. HBV integration additionally contributes to the production of HBV surface antigen (HBsAg), which is crucial for achieving a functional cure for HBV infection and influences the efficacy of antiviral treatments. Overall, HBV integration plays a pivotal role in hepatocarcinogenesis, and its detection via liquid biopsy will greatly enhance the clinical management of HBV-associated HCC.
Lyu et al. (2026) studied this question.