Diagnostic Performance of cfDNA-Based Liquid Biopsy for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Authors

Jiwei Liu, Yangyu Zhang, Shuo Yang, Yanhua Wu, Jing Jiang

Published in

Cancer science. Oct 20, 2026. Epub Oct 20, 2026.

Abstract

Conventional surveillance tools for hepatocellular carcinoma (HCC) have limited sensitivity. Circulating cell-free DNA (cfDNA)-based liquid biopsy is a promising minimally invasive approach; however, its overall diagnostic performance remains unclear. This meta-analysis aimed to comprehensively evaluate the diagnostic accuracy of cfDNA-based liquid biopsy in HCC. Following PRISMA-DTA guidelines, we searched PubMed, EMBASE, and Web of Science until July 2026. Diagnostic accuracy data were pooled using bivariate random-effects models. Methodological quality was assessed using QUADAS-2 and NOS. A total of 29 studies (4250 HCC patients, 7982 controls) were included. Pooled sensitivity and specificity of cfDNA-based testing were 0.82 (95% CI: 0.76-0.86) and 0.91 (95% CI: 0.88-0.93). The area under the summary receiver operating characteristic curve (AUC) was 0.93 (95% CI: 0.91-0.96). Subgroup analyses showed higher sensitivity in advanced HCC 0.91 (95% CI: 0.85-0.95) than early HCC 0.77 (95% CI: 0.71-0.83). Methylation profiling yielded relatively higher sensitivity 0.84 (95% CI: 0.77-0.89), whereas fragmentomics showed relatively favorable specificity 0.93 (95% CI: 0.88-0.96). Combining cfDNA-based testing with alpha-fetoprotein (AFP) significantly improved sensitivity compared with cfDNA alone (0.78 vs. 0.65). No significant publication bias was detected (p = 0.83). cfDNA-based liquid biopsy achieves high diagnostic accuracy for HCC. As exploratory observations, methylation-based assays with relatively higher sensitivity may have potential value for screening high-risk populations, while fragmentomics-based assays with relatively favorable specificity may aid differential diagnosis. Combining cfDNA-based liquid biopsy with AFP further improves diagnostic performance, supporting cfDNA as a promising noninvasive tool for HCC detection. Trial Registration: This systematic review was registered on PROSPERO: CRD420261293877 (https://www.crd.york.ac.uk/PROSPERO/).

PMID:
42902833
Bibliographic data and abstract were imported from PubMed on 22 Oct 2026.

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