{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T16:45:27Z","timestamp":1777481127244,"version":"3.51.4"},"reference-count":20,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Biotherapy and Radiopharmaceuticals"],"published-print":{"date-parts":[[2025,11]]},"abstract":"\n Objective:<\/jats:title>\n To demonstrate the diagnostic and prognostic value of combined detection of serum abnormal prothrombin II (PIVKA II), \u03b1-fetoprotein (AFP), and spliced variants of hepatitis B virus genomes (spHBV) in HBV-induced hepatocellular carcinoma (HCC).<\/jats:p>\n <\/jats:sec>\n \n Materials and Methods:<\/jats:title>\n From March 2018 to May 2019, samples were collected from 125 patients with HBV-related hepatocellular carcinoma (HBV-HCC), 125 patients with pure HBV (HBV group), and 125 patients with HBV-induced cirrhosis (HBV cirrhosis group), all of whom were receiving treatment at the hospital. Serum levels of PIVKA-II, AFP, and spHBV were measured using an immunochemiluminescence detection system, a fully automated immunoassay analyzer, and a real-time quantitative polymerase chain reaction instrument, respectively. Kaplan\u2013Meier method was applied to analyze relationship among serum PIVKA-II, AFP, spHBV, and prognosis of patients with HBV-HCC; cyclooxygenase (COX)\u00a0risk regression analyzed factors affecting prognosis of patients with HBV-HCC; receiver operating characteristic (ROC)\u00a0curve evaluated diagnostic and prognostic predictive efficacy of serum PIVKA-II, AFP, and spHBV alone or combined for HBV-HCC.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n The serum concentrations of PIVKA-II, AFP, and spHBV in the HBV-HCC group were significantly higher than those in the HBV cirrhosis group and the HBV group (all\n p<\/jats:italic>\n < 0.05). The HBV cirrhosis group also showed significantly higher levels compared with the HBV group (\n p<\/jats:italic>\n < 0.05). Serum PIVKA-II, AFP, spHBV, tumor number, tumor-node-metastasis (TNM) stage, and extrahepatic metastasis differed markedly between dead patients and surviving patients (\n p<\/jats:italic>\n < 0.05). PIVKA-II, AFP, and spHBV in patients with HBV-HCC were related to tumor number, TNM staging, and extrahepatic metastasis (\n p<\/jats:italic>\n < 0.05).The 36-month survival rate of patients with high-expression PIVKA-II was inferior to patients with low expression (\n \u03c7<\/jats:italic>\n 2<\/jats:sup>\n = 6.561,\n p<\/jats:italic>\n = 0.010); the 36-month survival rate of patients with high-expression AFP was inferior to patients with low expression (\n \u03c7<\/jats:italic>\n 2<\/jats:sup>\n = 4.789,\n p<\/jats:italic>\n = 0.029); and the 36-month survival rate of patients with high-expression spHBV was inferior to patients with low expression (\n \u03c7<\/jats:italic>\n 2<\/jats:sup>\n = 5.761,\n p<\/jats:italic>\n = 0.016). Multivariate logistic regression analysis showed that high expression of PIVKA-II, AFP, spHBV in serum, multiple tumors, TNM staging of stage III\u2013IV, and extrahepatic metastasis were all risk factors for death in patients with HBV-HCC (\n p<\/jats:italic>\n < 0.05). The area under the curve (AUC) of the combination of serum PIVKA-II, AFP, and spHBV in the diagnosis for HBV-HCC was markedly higher than PIVKA-II, AFP, and spHBV alone diagnosis (\n p<\/jats:italic>\n < 0.05). The AUC predicted by the combination of serum PIVKA-II, AFP, and spHBV in predicting the prognosis of patients with HBV-HCC was markedly higher than that predicted by the three factors alone (\n p<\/jats:italic>\n < 0.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n Serum PIVKA-II, AFP, and spHBV joint detection has significant clinical value for diagnosis and prognosis of HBV-HCC.<\/jats:p>\n <\/jats:sec>","DOI":"10.1089\/cbr.2025.0085","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T10:00:25Z","timestamp":1751450425000},"page":"613-621","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic and Prognostic Value of Combined Detection of Serum Protein Induced by Vitamin K Absence or Antagonist-II, Alpha-Fetoprotein, and Spliced Hepatitis B Virus in Hepatitis B Virus-Induced Hepatocellular Carcinoma"],"prefix":"10.1177","volume":"40","author":[{"given":"Zhentian","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, The First Clinical School of Guangdong Medical University, Zhanjiang, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haixing","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The Tenth Affiliated Hospital of Southern Medical University(Dongguan People\u2019s Hospital), Dongguan, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqing","family":"Yuan","sequence":"additional","affiliation":[{"name":"The First Clinical School of Guangdong Medical University, Zhanjiang, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9160-1263","authenticated-orcid":false,"given":"Wenjin","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Guangdong Medical University Affiliated Dongguan Houjie Hospital, Dongguan, China."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14223"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.678537"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13000-024-01528-8"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.13452"},{"issue":"20","key":"e_1_3_3_6_2","first-page":"2520","article-title":"Study on the application value of tumor markers PIVKA-II and AFP with fibrinolytic D-dimer and FDP detection in the diagnosis of primary liver cancer","volume":"33","author":"Jianfang H","year":"2023","unstructured":"Jianfang H, , Yi W, , Yi C, et al. Study on the application value of tumor markers PIVKA-II and AFP with fibrinolytic D-dimer and FDP detection in the diagnosis of primary liver cancer. Chinese Journal of Health Inspection, 2023; 33(20):2520\u20132523.","journal-title":"Chinese Journal of Health Inspection"},{"issue":"1","key":"e_1_3_3_7_2","first-page":"62","article-title":"Society of Infectious Diseases and Parasitic Diseases of Chinese Medical Association, Liver Disease Society of Chinese Medical Association. Viral hepatitis control program","volume":"40","year":"2001","unstructured":"Society of Infectious Diseases and Parasitic Diseases of Chinese Medical Association, Liver Disease Society of Chinese Medical Association. Viral hepatitis control program. Chinese Journal of Internal Medicine, 2001; 40(1):62\u201368.","journal-title":"Chinese Journal of Internal Medicine"},{"issue":"7","key":"e_1_3_3_8_2","first-page":"635","article-title":"Medical Administration Bureau of Health and Family Planning Commission, PRC. Practice for diagnosis and treatment of primary liver cancer (2017 edition)","volume":"16","year":"2017","unstructured":"Medical Administration Bureau of Health and Family Planning Commission, PRC. Practice for diagnosis and treatment of primary liver cancer (2017 edition). Chinese Journal of Digestive Surgery, 2017; 16(7):635\u2013647.","journal-title":"Chinese Journal of Digestive Surgery"},{"issue":"2","key":"e_1_3_3_9_2","first-page":"99","article-title":"Experts of the Joint Research Group of the Eleventh Five-Year Major Projects of the Ministry of Science and Technology. Clinical diagnosis, evaluation and integrated management of antiviral therapy in hepatitis B virus-related cirrhosis","volume":"30","year":"2014","unstructured":"Experts of the Joint Research Group of the Eleventh Five-Year Major Projects of the Ministry of Science and Technology. Clinical diagnosis, evaluation and integrated management of antiviral therapy in hepatitis B virus-related cirrhosis. Clinical Hepatobiliary Journal, 2014; 30(2):99\u2013109.","journal-title":"Clinical Hepatobiliary Journal"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/v14050986"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14475"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1752"},{"issue":"27","key":"e_1_3_3_13_2","first-page":"109","article-title":"Expression of serum PIVKA-II and AFP in patients with middle and advanced HCC and their predictive value for prognosis","volume":"21","author":"Yuanmin W","year":"2023","unstructured":"Yuanmin W. Expression of serum PIVKA-II and AFP in patients with middle and advanced HCC and their predictive value for prognosis. Chinese Medicine Guide, 2023; 21(27):109\u2013111. +115.","journal-title":"Chinese Medicine Guide"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.24823"},{"issue":"7","key":"e_1_3_3_15_2","first-page":"51","article-title":"Diagnostic value of AFP, AFP-L3 and PIVKA-II alone and combined test in early primary hepatocellular carcinoma","volume":"52","author":"Xuan Q","year":"2023","unstructured":"Xuan Q, , Yong Y, , Tao X, et al. Diagnostic value of AFP, AFP-L3 and PIVKA-II alone and combined test in early primary hepatocellular carcinoma. Journal of Medical Research, 2023; 52(7):51\u201355.","journal-title":"Journal of Medical Research"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep16459"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-03304-w"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(18)31197-8"},{"issue":"1","key":"e_1_3_3_19_2","first-page":"113","article-title":"Advances on molecular mechanism of hepatitis B virus-induced hepatocellular carcinoma","volume":"50","author":"Shao Y","year":"2021","unstructured":"Shao Y, , Su L, , Hao R, et al. Advances on molecular mechanism of hepatitis B virus-induced hepatocellular carcinoma. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2021; 50(1):113\u2013122.","journal-title":"Zhejiang Da Xue Xue Bao Yi Xue Ban"},{"issue":"4","key":"e_1_3_3_20_2","first-page":"412","article-title":"Predictive value of serum sHBV DNA and PIVKA-II combination test for HCC caused by HBV","volume":"25","author":"Fei L","year":"2020","unstructured":"Fei L, , Zhentian G, , Haixing M, et al. Predictive value of serum sHBV DNA and PIVKA-II combination test for HCC caused by HBV. Liver, 2020; 25(4):412\u2013415.","journal-title":"Liver"},{"issue":"3","key":"e_1_3_3_21_2","first-page":"3","article-title":"Predictive value of serum sHBV DNA combined with AFP for HBV","volume":"18","author":"Fei L","year":"2020","unstructured":"Fei L, , Zhentian G, , Haixing M, et al. Predictive value of serum sHBV DNA combined with AFP for HBV. 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