{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T20:33:13Z","timestamp":1773779593267,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cancers"],"abstract":"<jats:p>Background and Aims: Hepatocellular carcinoma (HCC) represents the second leading cause of cancer deaths worldwide. Six-month imaging along with alpha-fetoprotein (AFP) serum levels detection are the current gold standard to exclude HCC. Protein induced by vitamin K absence (PIVKA-II) has been proposed as a potential screening biomarker for HCC. This study was designed to evaluate the role of PIVKA-II as diagnostic HCC marker, and the correlation between PIVKA-II levels and HCC stage. Methods: PIVKA-II levels were assessed on serum samples of Italian patients. The study population included 80 patients with HCC, 111 with liver cirrhosis (LC), and 111 with chronic hepatitis C (CHC). Results: PIVKA-II serum levels progressively increase from patients with CHC to patients with HCC. In the HCC group, PIVKA-II values are higher in the more advanced stages of the disease, assessed by the Barcelona Clinic Liver Cancer (BCLC) staging system (BCLC-B vs. BCLC-A vs. BCLC-0). Youden\u2019s index analysis identified a value &gt;37 mAU\/mL as the optimal threshold for the best combination of sensitivity and specificity (80% and 76%, respectively) and, at the best cut-off of 5.2 ng\/mL, AFP yielded 53% specificity and 78% sensitivity. The combination of PIVKA-II and AFP reached positive and negative predictive values of 73.9% and 94.2%, respectively. Conclusions: PIVKA-II levels are increased in the HCC patients, compared to control groups. The increase is more evident in patients with advanced HCC. The diagnostic performance of PIVKA-II seems more sensitive than AFP while the combination of PIVKA-II and AFP resulted in the best diagnostic accuracy, reaching 73.9% positive predictive value and 94.2% negative predictive value, thus improving the diagnostic capability of the single marker.<\/jats:p>","DOI":"10.3390\/cancers17020167","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T05:06:34Z","timestamp":1736226394000},"page":"167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Diagnostic Performance of PIVKA-II in Italian Patients with Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4425-2499","authenticated-orcid":false,"given":"Valeria","family":"Guarneri","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Loggi","sequence":"additional","affiliation":[{"name":"Operational Unit of Clinical Pathology, ASUR4, 63900 Fermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Ramacieri","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5555-0745","authenticated-orcid":false,"given":"Carla","family":"Serra","sequence":"additional","affiliation":[{"name":"Interventional, Diagnostic and Therapeutic Ultrasound Unit, IRCCS AOUBO, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ranka","family":"Vukotic","sequence":"additional","affiliation":[{"name":"Department of Emergency and Acceptance, General Medicine IV, University Hospital of Pisa, 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2603-8245","authenticated-orcid":false,"given":"Giovanni","family":"Vitale","sequence":"additional","affiliation":[{"name":"Internal Medicine Unit for the Treatment of Severe Organ Failure, IRCCS AOUBO, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Scuteri","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmela","family":"Cursaro","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical, Maternal-Infantile and Adult Sciences, University of Modena and Reggio Emilia, 41126 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marzia","family":"Margotti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical, Maternal-Infantile and Adult Sciences, University of Modena and Reggio Emilia, 41126 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7930-1660","authenticated-orcid":false,"given":"Silvia","family":"Galli","sequence":"additional","affiliation":[{"name":"Microbiology Unit, IRCCS AOUBO, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Caracausi","sequence":"additional","affiliation":[{"name":"Unit of Histology, Embriology and Applied Biology, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7735-7847","authenticated-orcid":false,"given":"Lucia","family":"Brodosi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy"},{"name":"Clinical Nutrition and Metabolism Unit, IRCCS AOUBO, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filippo","family":"Gabrielli","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical, Maternal-Infantile and Adult Sciences, University of Modena and Reggio Emilia, 41126 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4794-9809","authenticated-orcid":false,"given":"Pietro","family":"Andreone","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical, Maternal-Infantile and Adult Sciences, University of Modena and Reggio Emilia, 41126 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 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