{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:04:58Z","timestamp":1792839898507,"version":"4.5.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T00:00:00Z","timestamp":1637280000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:p>\n                    Hepatocellular carcinoma (HCC), the sixth most common cancer worldwide, has an incidence rate equal to mortality. Over 80% of HCC cases occur within a high\u2010risk population, mainly patients with both cirrhosis and chronic hepatitis B or C. With a 5\u2010year survival rate ranging from &lt;16% for advanced HCC to &gt;90% for early stage HCC, there is a high medical need for the early detection of HCC. In this study, we systematically evaluated biomarkers mentioned in international guidelines and peer\u2010reviewed literature for HCC surveillance and diagnosis with the aim of identifying combinations that display high sensitivity and specificity for early stage HCC. Fifty biomarkers were measured in the first sample panel, panel A (n\u00a0=\u00a0110), and subjected to univariate analysis. Of these, 35 biomarkers (38 assays) from panel A and an additional 13 biomarkers from the literature were prioritized for subsequent multivariate evaluation with lasso regression and exhaustive search of two\u2010 to four\u2010biomarker combinations (panel B). Panel B included 1,081 samples from patients with HCC (n\u00a0=\u00a0308) or with chronic liver diseases (n\u00a0=\u00a0740). Among all patients, 61.0% had hepatitis B, 32.9% had hepatitis C, and 60.5% had cirrhosis; 40.6% of patients with HCC had early stage cancer. Protein induced by vitamin K absence\u2010II (PIVKA\u2010II; also known as des\u2010gamma\u2010carboxy prothrombin [DCP]) and alpha\u2010fetoprotein (AFP) demonstrated the best clinical performance, both individually and in combination, and the addition of a third biomarker (\n                    <jats:italic toggle=\"yes\">Lens culinaris<\/jats:italic>\n                    agglutinin\u2010reactive fraction of AFP [AFP\u2010L3], cartilage oligomeric matrix protein [COMP], insulin\u2010like growth factor\u2010binding protein 3 [IGFBP3], or matrix metalloproteinase 3 [MMP3]) further increased sensitivity for the detection of both early stage and all\u2010stage HCC. The addition of age and sex to the three\u2010biomarker panel resulted in an improved diagnostic performance.\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    The combination of AFP and PIVKA\u2010II, with either IGFBP3, COMP or MMP3, plus age and sex, demonstrated the best performance for the detection of early\u2010 and all\u2010stage HCC. These novel panels performed similar to that of the GALAD score (sex [gender], age, plus serum levels of AFP, AFP\u2010L3 and DCP [PIVKA\u2010II]), a promising screening tool developed for HCC detection.\n                  <\/jats:p>","DOI":"10.1002\/hep4.1847","type":"journal-article","created":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T03:46:08Z","timestamp":1637293568000},"page":"679-691","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":61,"title":["Multimarker Panels for Detection of Early Stage Hepatocellular Carcinoma: A Prospective, Multicenter, Case\u2010Control Study"],"prefix":"10.1097","volume":"6","author":[{"given":"Teerha","family":"Piratvisuth","sequence":"first","affiliation":[{"name":"NKC Institute of Gastroenterology and Hepatology,Songklanagarind Hospital,Prince of Songkla University,Hat Yai,Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tawesak","family":"Tanwandee","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology,Faculty of Medicine,Siriraj Hospital,Mahidol University,Bangkok,Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satawat","family":"Thongsawat","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine,Maharaj Nakorn Chiang Mai Hospital,Chiang Mai University,Chiang Mai,Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wattana","family":"Sukeepaisarnjaroen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine,Srinagarind Hospital,Khon Kaen University,Khon Kaen,Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Ignacio","family":"Esteban","sequence":"additional","affiliation":[{"name":"Liver Unit,Hospital Universitari Vall d\u2019Hebron,Barcelona,Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en red de Enfermedades Hep\u00e1ticas y Digestivas,Insituto de Salud Carlos III,Madrid,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Bes","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en red de Enfermedades Hep\u00e1ticas y Digestivas,Insituto de Salud Carlos III,Madrid,Spain"},{"name":"Transfusion Safety Laboratory,Banc de Sang i Teixits,Barcelona,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"K\u00f6hler","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology,National Center for Tumor Diseases,University Hospital Heidelberg,Heidelberg,Germany"},{"name":"Liver Cancer Center Heidelberg,Heidelberg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"He","sequence":"additional","affiliation":[{"name":"Roche Diagnostics GmbH,Penzberg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Swiatek\u2010de Lange","sequence":"additional","affiliation":[{"name":"Roche Diagnostics GmbH,Penzberg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Morgenstern","sequence":"additional","affiliation":[{"name":"Roche Diagnostics Operations,Indianapolis,IN,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry Lik\u2010Yuen","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics,Chinese University of Hong Kong,Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,11,19]]},"reference":[{"key":"hep41847-bib-0001-20241115","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.soc.2014.09.001","article-title":"Epidemiology of hepatocellular 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