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

Xiumei Wang,Zhihua Wang,Youde Liu,Xiangshuo Kong,Ping Sun,Weiwei Zhang,Miaomiao Yang,Wenjing Gong

doi:10.1186/s13027-017-0153-6

Abstract

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.

Highlights

To 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)
The results showed that for those AFP-negative HCC patients, the area under receiver operator curve (ROC) curve (AUROC) for PIVKA-II was 0.73 (95%CI 0.640–0.815, P < 0.001, Fig. 2b)
Diagnostic value of PIVKA-II in patients with small HCC Among HCC patients diagnosed with small HCC, the AUROC of PIVKA- II was 0.692 (95%CI 0.597–0.788, P < 0.001, Fig. 2a)

Summary

Introduction

To 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). For the patients diagnosed at early stage of HCC, the 5-year survival rate is >70% [1]. Diagnosis of early stage HCC is heavily dependent on radiological imaging technique, which does not provide sufficient sensitivity. Biological markers in serum may facilitate the early diagnosis of HCC, improving survival rate. The sensitivity and specificity of diagnosis at early stage of HCC are still far from ideal [2]. There have been efforts in identification of new biomarkers for the early diagnosis of HCC. Various factors such as des-γcarboxyprothrombin, AFP-L3, glypican-3, osteopontin, Golgi protein-73 and a number of microRNAs have been suggested to be potential markers [1, 3]

Methods

Results

Discussion

Conclusion