Protein induced by vitamin K absence or antagonist-II (PIVKA-II) specifically increased in Italian hepatocellular carcinoma patients

Viggiani, Valentina; Gennarini, Giuseppina; d’Ettorre, Gabriella; Vito, Corrado De; Angeloni, Antonio; Frati, Luigi; Anastasi, Emanuela

doi:10.1080/00365521.2016.1183705

Cited by 21 publications

(18 citation statements)

References 27 publications

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“…The results showed that combination of PIVKA-II and AFP further increase the efficiency for diagnosis of HBV related early stage HCC. This result was also in consistent with a few other studies using combination of the two markers as diagnostic marker of HCC [ 14 ].…”

Section: Discussionsupporting

confidence: 93%

“…Although PIVKA-II is mainly used as a diagnostic marker in Asia, studies in other populations, including Middle Eastern and European subjects, have also demonstrated its diagnostic value for HCC [ 11 – 13 ]. There has also been report that combination of PIVKA-II with other biomarkers may further increase the sensitivity and specificity for early diagnosis of HCC [ 14 ]. The PIVKA-II level has also recently drawn interest as a prognostic marker for HCC patients [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Diagnostic value of prothrombin induced by the absence of vitamin K or antagonist-II (PIVKA-II) for early stage HBV related hepatocellular carcinoma

Wang

Zhang

Liu

et al. 2017

Infect Agents Cancer

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BackgroundTo evaluate the diagnostic efficacy of prothrombin induced by the absence of vitamin K or antagonist-II (PIVKA-II) for early stage hepatitis virus B (HBV) related hepatocellular carcinoma (HCC).MethodsSerums levels of PIVKA-II and a-Fetoprotein (AFP) was detected and compared in 113 patients with clinical confirmed Barcelona Clinic Liver Cancer (BCLC) stage 0-A HBV-related HCC and 161 chronic hepatitis B (CHB) patients. Diagnostic efficiencies as well as cut-off values of PIVKA-II, AFP and combination of the two markers were calculated using receiver operator curve (ROC) analysis.ResultsThe mean level of PIVKA-II among HCC patients were 79.64 ± 149.88, significantly higher than control group (P < 0.001). ROC results showed that among those AFP-negative HCC patients, the area under ROC curve (AUROC) of PIVKA-II was 0.73 (95%CI 0.640–0.815, P < 0.001). Among HCC patients diagnosed with small HCC (tumor size ≤2 cm), the AUROC of PIVKA- II was 0.692 (95%CI 0.597–0.788, P < 0.001). To evaluate the diagnostic value of PIVKA-II in HCC patient, all CHB cases were pooled together as control for analysis. The AUROC of PIVKA-II was 0.756 (95%CI 0.698–0.814, P < 0.001), and the optimal cutoff value of PIVKA-II was 32.09 mAU/ml with sensitivity of 52.21% and specificity of 81.49%. When serum levels of PIVKA-II and AFP were combined to obtain a new marker for HCC diagnosis, PIVKA-II + AFP further increased diagnostic efficiency, with AUROC of 0.868 (95%CI 0.822–0.913), higher than that of AFP (P < 0.01) or PIVKA-II (P < 0.001) alone. In addition, we found that HCC patients in poorly differentiated- undifferentiated group and in microvascular invasion group had higher levels of PIVKA-II. Multivariate analysis showed that high serum PIVKA-II level (OR = 1.003, 95%CI 1.001–1.007, P = 0.047) was an independent risk factor for microvascular invasion in HCC patients.ConclusionSerum PIVKA-II level is a potential marker for early diagnosis of HCC and microvascular invasion. The use of PIVKA-II may improve assessment of tumor prognosis and guide development of therapeutic strategy.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Diagnostic value of prothrombin induced by the absence of vitamin K or antagonist-II (PIVKA-II) for early stage HBV related hepatocellular carcinoma

Wang

Zhang

Liu

et al. 2017

Infect Agents Cancer

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“…Prothrombin induced by vitamin K absence II and CEA serum concentrations were determined on a Lumipulse G1200 (Fujirebio-Europe, Gent, Belgium), using the LUMIPULSE G PIVKA-II kit and the LUMIPULSE G CEA kit (Fujirebio, Tokyo, Japan) respectively ( 17 ). Lumipulse G1200 is a fully automated assay system for the quantitative measurement in serum specimen based on chemiluminescent enzyme immunoassay (CLEIA) technology by a two-step sandwich in immunoreaction cartridges.…”

Section: Methodsmentioning

confidence: 99%

Protein Induced by Vitamin K Absence II (PIVKA-II) as a potential serological biomarker in pancreatic cancer: a pilot study

Tartaglione

Pecorella

Zarrillo

et al. 2019

Biochem. med. (Online)

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Introduction: Protein induced by vitamin K absence II (PIVKA-II) is an abnormal prothrombin increased in gastrointestinal malignancy. We aimed to evaluate PIVKA-II in comparison to established pancreatic cancer (PC) biomarkers (CA 19-9, carcinoembryonic antigen (CEA) and CA 242) measured in PC patients and in patients with benign pancreatic diseases. Materials and methods: We studied 26 PC patients (Group 1) and 20 patients with benign pancreatic diseases (Group 2). PIVKA-II and CEA were measured by chemiluminescent enzyme immunoassay method (CLEIA) on LUMIPULSE G1200 (Fujirebio-Europe, Gent, Belgium), CA 19-9 and CA 242 were measured by ELSA (CisBio Bioassays, Codolet, France) and EIA (Fujirebio Diagnostics AB, Göteborg, Sweden), respectively. Receiver operating characteristic (ROC) analysis was performed to assess biomarkers’ diagnostic characteristics in both groups. Results: Median and interquartile range (IQR) in Group 1 and Group 2 were: 1749.0 (320.2 – 3921.0) vs. 31.0 (23.0 – 43.0) mAU/mL (P < 0.001) for PIVKA-II, 260.0 (158.7 – 272.0) vs. 45.2 (9.0 – 58.0) U/mL (P = 0.034) for CA 19-9, 104.0 (30.2 – 150.0) vs. 7.2 (4.8 – 26.0) U/mL (P < 0.050) for CA 242, 9.4 (5.3 – 37.5) vs. 4.5 (1.8 – 7.0) ng/mL (P = 0.021) for CEA. Areas under the ROC curve of PIVKA-II, CA 19-9, CA 242, CEA were 0.86 (95% CI: 0.71 – 1.00), 0.58 (95% CI: 0.38 – 0.78), 0.73 (95% CI: 0.54 – 0.92), 0.64 (95% CI: 0.44 – 0.85), respectively. Conclusions: PIVKA-II is significantly higher in PC than in benign pancreatic diseases. PIVKA-II shows a rather good diagnostic performance compared to CA 19-9, CEA and CA242, thus its determination could help PC management.

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“…However, owing to its low sensitivity and specificity, AFP testing alone is not recommended in diagnostic assessments of HCC [ 3 – 10 ]. Instead, it is used to combine with other serum or plasma tumor markers, which have been shown to have superior diagnostic abilities [ 3 , 6 , 11 – 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…The role of DCP as a biomarker of HCC was first reported in a study published 1984 [ 17 ], which found that DCP was present in 91% of HCC patients but not detectable in other benign liver diseases. Subsequently, numerous studies [ 6 – 8 , 13 , 18 – 20 ] demonstrated that a combined analysis of DCP and AFP led to better prediction of HCC although there are some controversies about the diagnostic accuracy of DCP + AFP.…”

Section: Introductionmentioning

confidence: 99%

Combining des-gamma-carboxyprothrombin and alpha-fetoprotein for hepatocellular carcinoma diagnosing: an update meta-analysis and validation study

Chen

et al. 2017

Oncotarget

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Controversies about the combination of des-gamma-carboxyprothrombin (DCP) and alpha-fetoprotein (AFP) for hepatocellular carcinoma diagnosing still exist. Hence, we performed this updated meta-analysis to estimate the diagnostic value of DCP , AFP and DCP + AFP in HCC. In addition, we conducted a validation study to analyze the performance of the candidate makers. After a systematic literature review, 27 studies from 20 articles were identified from four major databases. The pooled sensitivity and specificity were 69% and 89%, respectively, for DCP; for AFP, they were 65% and 88%, respectively; and they were 82% and 85%, respectively, for DCP + AFP. The values of the area under the curve (AUC) for DCP, AFP, DCP + AFP, respectively, were 0.88, 0.75, and 0.90. The validation study confirmed that the performance of DCP + AFP (sensitivity = 84%, specificity = 86%; AUC = 0.887) was higher than that of DCP (sensitivity = 76%, specificity = 92%; AUC = 0.843) or AFP (sensitivity = 73%, specificity = 92%; AUC = 0.837) alone.

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Protein induced by vitamin K absence or antagonist-II (PIVKA-II) specifically increased in Italian hepatocellular carcinoma patients

Abstract: The combination of the two biomarkers, evaluated by the ROC analysis, improved the specificity compared to a single marker. These data suggest that the combined analysis of the two markers could be a useful tool in clinical practice.

Cited by 21 publications

References 27 publications

Diagnostic value of prothrombin induced by the absence of vitamin K or antagonist-II (PIVKA-II) for early stage HBV related hepatocellular carcinoma

Diagnostic value of prothrombin induced by the absence of vitamin K or antagonist-II (PIVKA-II) for early stage HBV related hepatocellular carcinoma

Protein Induced by Vitamin K Absence II (PIVKA-II) as a potential serological biomarker in pancreatic cancer: a pilot study

Combining des-gamma-carboxyprothrombin and alpha-fetoprotein for hepatocellular carcinoma diagnosing: an update meta-analysis and validation study

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