AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025260275
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REVIEW ARTICLE

Circulating cell-free DNA in clinical management of hepatocellular carcinoma: Updates on detection, diagnosis, treatment, and recurrence

Zita Hoi-Ying Chan1 ,  Xueying Lyu1 ,  Daniel Wai-Hung Ho1*
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1 Department of Pathology and State Key Laboratory of Liver Research, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China
EJMO, 025260275 https://doi.org/10.36922/EJMO025260275
Received: 25 June 2025 | Revised: 22 August 2025 | Accepted: 19 September 2025 | Published online: 27 October 2025
© 2025 by the Authoir(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

The evident concordance between tissue and liquid biopsies in hepatocellular carcinoma (HCC), a prevalent and lethal cancer worldwide, has positioned liquid biopsy as a valuable non-invasive tool for the clinical management of HCC. Among its analytes, circulating cell-free DNA (cfDNA) has recently gained significant attention as a key biomarker for HCC. This review provides an overview of recent advancements in the use of cfDNA for the detection and diagnosis, treatment decision-making, and recurrence surveillance of HCC. The various merits of cfDNA underscore its strong potential for clinical integration in HCC. However, there is also an emerging imperative that arises from the varying cfDNA-related methodologies, which demonstrate disparate outcomes across studies, emphasizing the importance of systematic evaluation and standardization to ensure consistent and equitable patient care.

Keywords
Hepatocellular carcinoma
Circulating cell-free DNA
Machine learning
Tumor burden
Funding
This work was supported by the Hong Kong Research Grants Council Theme-based Research Scheme (T12-716/22-R), Innovation and Technology Commission grant to State Key Laboratory of Liver Research (ITC PD/17-9), Health and Medical Research Fund (10212956 & 07182546), and RGC General Research Fund (17100021 & 17117019).
Conflict of interest
Daniel Wai-Hung Ho is an Editorial Board Member of this journal and serves as the Guest Editor of this special issue, but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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