Clin Mol Hepatol.
2025 Feb;31(Suppl):S255-S284. 10.3350/cmh.2024.0541.
Liquid biopsy in hepatocellular carcinoma: Challenges, advances, and clinical implications
- Park J1
- Lee YT1,2
- Agopian VG3,4
- Liu JS5
- Koltsova EK6
- You S7,8
- Zhu Y3,9,10
- Tseng HR3,9
- Yang JD
1,8,11
- Affiliations
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- 1Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- 2Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- 3Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA
- 4Department of Surgery, University of California Los Angeles, Los Angeles, CA, USA
- 5Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA
- 6Smidt Heart Institute, Department of Medicine, Department of Biomedical Sciences, 8700 Beverly Blvd, Los Angeles, CA, USA
- 7Department of Urology and Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- 8Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- 9California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, USA
- 10Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA, USA
- 11Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- KMID: 2565381
- DOI: http://doi.org/10.3350/cmh.2024.0541
Abstract
- Hepatocellular carcinoma (HCC) is an aggressive primary liver malignancy often diagnosed at an advanced stage, resulting in a poor prognosis. Accurate risk stratification and early detection of HCC are critical unmet needs for improving outcomes. Several blood-based biomarkers and imaging tests are available for early detection, prediction, and monitoring of HCC. However, serum protein biomarkers such as alpha-fetoprotein have shown relatively low sensitivity, leading to inaccurate performance. Imaging studies also face limitations related to suboptimal accuracy, high cost, and limited implementation. Recently, liquid biopsy techniques have gained attention for addressing these unmet needs. Liquid biopsy is non-invasive and provides more objective readouts, requiring less reliance on healthcare professional’s skills compared to imaging. Circulating tumor cells, cell-free DNA, and extracellular vesicles are targeted in liquid biopsies as novel biomarkers for HCC. Despite their potential, there are debates regarding the role of these novel biomarkers in the HCC care continuum. This review article aims to discuss the technical challenges, recent technical advancements, advantages and disadvantages of these liquid biopsies, as well as their current clinical application and future directions of liquid biopsy in HCC.
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