Developments and current status of cell-free DNA in the early detection and management of hepatocellular carcinoma

Nowadays, hepatocellular carcinoma (HCC) is still a major threat to human health globally, with a disappointing prognosis. Regular monitoring of patients at high risk, utilizing abdominal ultrasonography combined with alpha-fetoprotein (AFP) serum analysis, enables the early detection of potentially treatable tumors. However, the approach has limitations due to its lack of sensitivity. Meanwhile, the current standard procedure for obtaining a tumor biopsy in cases of HCC is invasive and lacks the ability to assess the dynamic progression of cancer or account for tumor heterogeneity. Hence, there is a pressing need to develop non-invasive, highly sensitive biomarkers for HCC which can improve the accuracy of early diagnosis, assess treatment response and accurately predict the prognosis. In contrast to the conventional method of tissue biopsy, liquid biopsy offers a non-invasive approach that can be readily repeated. As a liquid biopsy approach, the analysis of cell-free DNA (cfDNA) offers real-time insights that can accurately portray the tumor burden and provide a comprehensive depiction of the genetic profile associated with HCC. In this review, we present a comprehensive summary of the recent research findings pertaining to the significance and potential practicality of cfDNA analysis in the early detection and effective management of HCC.