Hepatocellular carcinoma (HCC) remains a major global health challenge, characterized by high incidence, late diagnosis, and frequent recurrence despite curative-intent treatments. Conventional tools for disease monitoring, including imaging modalities and serum biomarkers such as alpha-fetoprotein, have significant limitations in accurately capturing tumor dynamics and early molecular changes.
Circulating tumor DNA (ctDNA), a tumor-derived fraction of cell-free DNA, has emerged as a promising non-invasive biomarker that reflects the real-time molecular landscape of HCC. Recent advances in liquid biopsy technologies have enabled the detection of tumor-specific genetic and epigenetic alterations, offering new opportunities for dynamic disease monitoring.
In this review, we provide a comprehensive overview of the biological basis, detection technologies, and clinical applications of ctDNA in HCC, with a particular focus on its role in treatment monitoring and minimal residual disease (MRD) detection. Accumulating evidence suggests that ctDNA dynamics correlate with tumor burden and treatment response, and may allow earlier detection of recurrence compared to conventional methods. In addition, emerging approaches such as methylation-based assays, fragmentomics, and tumor-informed platforms are improving detection sensitivity, particularly in the context of low tumor DNA shedding. Despite its considerable potential, several challenges—including low ctDNA abundance, lack of assay standardization, and limited prospective validation—continue to hinder its routine clinical implementation.
In conclusion, ctDNA represents a highly promising biomarker in HCC, with the potential to transform treatment monitoring and precision oncology strategies. Future integration with multi-omics approaches and artificial intelligence, along with large-scale prospective studies, will be critical to establish its role in clinical practice.
Keywords: Hepatocellular carcinoma, Circulating tumor DNA, Liquid biopsy, Treatment monitoring, Minimal residual disease
Citation: Topal, U., & Sarıtaş, A. G. (2026). Circulating Tumor DNA in Hepatocellular Carcinoma: Current Status and Emerging Role in Treatment Monitoring. J Sur & Surgic Proce.,4(2):1-9.
DOI : https://doi.org/10.47485/3069-8154.1033