{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T06:43:51Z","timestamp":1792565031888,"version":"4.5.0"},"reference-count":47,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100011789","name":"Department of Science and Technology of Jilin Province","doi-asserted-by":"publisher","award":["YDZJ202401443ZYTS"],"award-info":[{"award-number":["YDZJ202401443ZYTS"]}],"id":[{"id":"10.13039\/501100011789","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373664"],"award-info":[{"award-number":["82373664"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Conventional surveillance tools for hepatocellular carcinoma (HCC) have limited sensitivity. Circulating cell\u2010free DNA (cfDNA)\u2010based liquid biopsy is a promising minimally invasive approach; however, its overall diagnostic performance remains unclear. This meta\u2010analysis aimed to comprehensively evaluate the diagnostic accuracy of cfDNA\u2010based liquid biopsy in HCC. Following PRISMA\u2010DTA guidelines, we searched PubMed, EMBASE, and Web of Science until July 2026. Diagnostic accuracy data were pooled using bivariate random\u2010effects models. Methodological quality was assessed using QUADAS\u20102 and NOS. A total of 29 studies (4250 HCC patients, 7982 controls) were included. Pooled sensitivity and specificity of cfDNA\u2010based testing were 0.82 (95% CI: 0.76\u20130.86) and 0.91 (95% CI: 0.88\u20130.93). The area under the summary receiver operating characteristic curve (AUC) was 0.93 (95% CI: 0.91\u20130.96). Subgroup analyses showed higher sensitivity in advanced HCC 0.91 (95% CI: 0.85\u20130.95) than early HCC 0.77 (95% CI: 0.71\u20130.83). Methylation profiling yielded relatively higher sensitivity 0.84 (95% CI: 0.77\u20130.89), whereas fragmentomics showed relatively favorable specificity 0.93 (95% CI: 0.88\u20130.96). Combining cfDNA\u2010based testing with alpha\u2010fetoprotein (AFP) significantly improved sensitivity compared with cfDNA alone (0.78 vs. 0.65). No significant publication bias was detected (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.83). cfDNA\u2010based liquid biopsy achieves high diagnostic accuracy for HCC. As exploratory observations, methylation\u2010based assays with relatively higher sensitivity may have potential value for screening high\u2010risk populations, while fragmentomics\u2010based assays with relatively favorable specificity may aid differential diagnosis. Combining cfDNA\u2010based liquid biopsy with AFP further improves diagnostic performance, supporting cfDNA as a promising noninvasive tool for HCC detection.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    This systematic review was registered on PROSPERO: CRD420261293877 (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.crd.york.ac.uk\/PROSPERO\/\">https:\/\/www.crd.york.ac.uk\/PROSPERO\/<\/jats:ext-link>\n                    )\n                  <\/jats:p>","DOI":"10.1111\/cas.70551","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T05:58:51Z","timestamp":1792562331000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic Performance of\n                    <scp>cfDNA<\/scp>\n                    \u2010Based Liquid Biopsy for Hepatocellular Carcinoma: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6033-246X","authenticated-orcid":false,"given":"Jiwei","family":"Liu","sequence":"first","affiliation":[{"name":"Meihe Health Research Institute The First Hospital of Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Meihe Health Research Institute The First Hospital of Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Wu","sequence":"additional","affiliation":[{"name":"Meihe Health Research Institute The First Hospital of Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9714-9255","authenticated-orcid":false,"given":"Jing","family":"Jiang","sequence":"additional","affiliation":[{"name":"Meihe Health Research Institute The First Hospital of Jilin University  Changchun 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