{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:57:14Z","timestamp":1772992634027,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K17463"],"award-info":[{"award-number":["19K17463"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2026,3]]},"abstract":"ABSTRACT<\/jats:title>\n \n Aim<\/jats:title>\n \n The incidence of nonviral hepatocellular carcinoma (N\u2010HCC) is increasing due to improvements in hepatitis control. Patients are often diagnosed at an advanced stage owing to a lack of surveillance systems. We previously reported the usefulness of a liquid biopsy test based on a sensitive methylated\n septin 9<\/jats:italic>\n (m\u2010\n SEPT9<\/jats:italic>\n ) assay for detecting HCC. In this study, we validated the diagnostic ability of m\u2010\n SEPT9<\/jats:italic>\n and developed a novel integrated index to improve HCC prediction.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A total of 1450 samples (464 healthy individuals, 202 patients with chronic liver disease without HCC, and 784 patients with HCC) were analyzed using the combined restriction digital polymerase chain reaction assay for m\u2010\n SEPT9<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The sensitivity and specificity of m\u2010\n SEPT9<\/jats:italic>\n were 68.1% (95% confidence interval [CI], 0.649\u20130.714) and 84.9% (95% CI: 0.817\u20130.882), respectively, with an area under the curve (AUC) of 0.831; however, the lower limit of the 95% CI for specificity did not exceed the threshold of our setting (> 85%). Multivariable analysis identified age, sex, des\u2010gamma carboxy prothrombin, alpha\u2010fetoprotein, and m\u2010\n SEPT9<\/jats:italic>\n as independent diagnostic markers. Based on these markers, the ASDAm\u2010S9 index was developed, demonstrating a sensitivity of 89.9% and specificity of 90.9% (healthy individuals vs. HCC, AUC: 0.961), regardless of HCC etiology or stage.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n The diagnostic performance of m\u2010\n SEPT9<\/jats:italic>\n alone could not be fully verified; however, the ASDAm\u2010S9 index demonstrated excellent accuracy for detecting HCC, including its early stages. This index shows promise as a blood\u2010based cancer screening tool for early\u2010stage HCC in the general population.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/hepr.70072","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T09:56:41Z","timestamp":1763459801000},"page":"359-367","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Validation of Liquid Biopsy Using a Methylated\n SEPT9<\/i>\n Assay and Integrated Index for Detecting Hepatocellular Carcinoma"],"prefix":"10.1111","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5885-5042","authenticated-orcid":false,"given":"Issei","family":"Saeki","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Yamaguchi University Graduate School of Medicine Ube 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