{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:39:34Z","timestamp":1787747974539,"version":"build-2784847793"},"reference-count":29,"publisher":"The Korean Association for the Study of the Liver","issue":"3","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["e-cmh.org"],"crossmark-restriction":true},"short-container-title":["Clin Mol Hepatol"],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:p>Background\/Aims: The GALAD (Gender, Age, Lens culinaris agglutinin-reactive alpha-fetoprotein [AFP-L3], alpha-fetoprotein [AFP], and des-\u03b3-carboxy prothrombin) score, widely used for hepatocellular carcinoma (HCC) detection, was primarily derived from cohorts with advanced-stage tumors and elevated biomarker levels, potentially overestimating accuracy in early-stage disease. Furthermore, the lectin-based AFP-L3 assay has poor sensitivity at low AFP concentrations, limiting detection of small or AFP-negative tumors.Methods: We developed GAFAD, a multivariable model replacing AFP-L3 with fucosylated AFP percentage, quantified by a validated liquid chromatography\u2013tandem mass spectrometry assay. The model was trained and tested using a hepatitis B virus (HBV)-related cohort (HCC n=235; non-HCC n=290), a diagnostically challenging set with substantial overlap in biomarker levels between HCC and non-HCC. Moreover, a final model (GAFAD) was validated in two independent cohorts (HCC n=210; non-HCC n=245), comprising HBV-, HCV-related and non-viral etiologies.Results: In the development cohort, GAFAD showed superior diagnostic performance to GALAD for distinguishing HCC from non-HCC, with a higher area under the receiver operating characteristic curve (AUC, 0.938 vs. 0.887; &lt;i&gt;P&lt;\/i&gt;&lt;0.0001) and greater sensitivity (82% vs. 66%) and accuracy (86% vs. 79%) at 90% specificity. In the external validation cohort, GAFAD similarly outperformed GALAD, achieving a higher AUC (0.874 vs. 0.841, &lt;i&gt;P&lt;\/i&gt;&lt;0.05), greater sensitivity (72% vs. 57%), and improved accuracy (82% vs. 75%) at 90% specificity. This superiority extended to early-stage, very-early-stage, and AFP-negative HCC.Conclusions: GAFAD provides a reliable and generalizable tool for early HCC detection across diverse etiologies, supporting its clinical applicability in surveillance and diagnosis.<\/jats:p>","DOI":"10.3350\/cmh.2025.1244","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T23:25:43Z","timestamp":1772061943000},"page":"1225-1239","update-policy":"https:\/\/doi.org\/10.3350\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["GAFAD: A liquid chromatography-tandem mass spectrometry-based model for early hepatocellular carcinoma detection beyond GALAD\u2019s limitations"],"prefix":"10.3350","volume":"32","author":[{"given":"Hyojin","family":"Kim","sequence":"first","affiliation":[{"name":"R&D Center for Clinical Mass Spectrometry, Seegene Medical Foundation, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wonseok","family":"Oh","sequence":"additional","affiliation":[{"name":"R&D Center for Clinical Mass Spectrometry, Seegene Medical Foundation, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juri","family":"Park","sequence":"additional","affiliation":[{"name":"R&D Center for Clinical Mass Spectrometry, Seegene Medical Foundation, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeyoung","family":"Lee","sequence":"additional","affiliation":[{"name":"R&D Center for Clinical Mass Spectrometry, Seegene Medical Foundation, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Suk","family":"Yang","sequence":"additional","affiliation":[{"name":"R&D Center for Clinical Mass Spectrometry, Seegene Medical Foundation, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soon 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