Value of AFP and PIVKA-II in diagnosis of HBV-related hepatocellular carcinoma and prediction of vascular invasion and tumor differentiation

Abstract

Background To explore the value of alpha fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) in diagnosis of HBV-related hepatocellular carcinoma (HCC) and their relationship with vascular invasion, tumor differentiation and size. Methods A total of 433 participants were enrolled in this study including 266 cases with HBV-related HCC, 87 cases with HBV DNA positive benign liver disease and 80 healthy individuals. Then we explored the correlation between AFP, PIVKA-II serum level and several pathological features such as vascular invasion, tumor differentiation and size. The value of these two markers used singly or jointly in diagnosing HBV-related HCC was evaluated by receiver operating characteristic (ROC) curve. The ROC curve was also plotted to identify AFP, PIVKA-II serum cut-off values that would best distinguish HBV-related HCC patients with and without vascular invasion. Results The level of AFP and PIVKA-II in HBV-related HCC group was significantly higher (Z was 7.428, 11.243 respectively, all P < 0.01). When AFP and PIVKA-II were used as the individual tumor marker, the areas under the ROC curve (AUC) of HBV-related HCC diagnosis were 0.765 (95% CI, 0.713 ~ 0.8170) for AFP, 0.901 (95% CI, 0.868 ~ 0.935) for PIVKA-II, and 0.917 (95% CI, 0.886 ~ 0.948) for AFP and PIVKA-II simultaneously. The serum levels of AFP and PIVKA-II were positively correlated with tumor differentiation and size. High AFP and PIVKA-II expression was significantly associated with the presence of vascular invasion (P was 0.007 and 0.014 respectively). The AFP level > 64.4 ng/ml or PIVKA-II level > 957.61mAU/ml was the best critical value to predict the presence of vascular invasion. Conclusion Our results validate that AFP and PIVKA-II play a significant role in the diagnosis of HBV-related HCC. The diagnostic value of AFP and PIVKA-II combined detection or single assay of PIVKA-II is higher than that of separate assay of AFP. Moreover, their concentration has important clinical value in judging tumor size, tumor cell differentiation and vascular invasion.

Clinical Value Evaluation of microRNA-324-3p and Other Available Biomarkers in Patients With HBV Infection–Related Hepatocellular Carcinoma

“…Thus, early diagnosis is critical to predict HCC in patients with HBV infection. So far, many serological biomarkers have been developed for HCC diagnosis, and alpha-fetoprotein (AFP) and protein induced by vitamin K absence/antagonist II (PIVKA-II) are widely used in clinical practice [ 6 , 7 ]. However, many HCC patients had normal AFP levels, while high AFP levels (>200 ng/mL) could be found in those with non-HCC conditions [ 8 ].…”

Progression of Prothrombin Induced by Vitamin K Absence-II in Hepatocellular Carcinoma

“…In addition, serum PIVKA-II levels were related to tumor size, tumor cell differentiation, and BCLC staging (P <0.05) (108). Si et al reported that the serum levels of PIVKA-II were significantly different in well, moderate, or poor differentiation HCC (108).…”

“…Suk-Won Suh et al reported that the level of PIVKA-II≥800 mAU/ml could predict micrometastases and poor prognosis (HR=5.166; 95% CI, 1.031-25.897) (112). In addition, serum PIVKA-II levels were related to tumor size, tumor cell differentiation, and BCLC staging (P <0.05) (108). Si et al reported that the serum levels of PIVKA-II were significantly different in well, moderate, or poor differentiation HCC (108).…”

Unique Features of Hepatitis B Virus-Related Hepatocellular Carcinoma in Pathogenesis and Clinical Significance

“…A more applicable serum biomarker, α-fetoprotein (AFP), has high detection specificity of 80–90% but with low sensitivity of 40–65% [ 128 , 134 ]. To improve the diagnostic accuracy of early HBV-related HCC tumors, another serum biomarker, namely, protein induced by vitamin K absence or antagonists-II (PIVKA-II), had been practically evaluated in large cohort studies for combinatorial use with AFP, although the detection sensitivity and specificity for tumors <2 cm was only marginally improved [ 135 , 136 , 137 ]. Moreover, numerous serum proteins and microRNAs (miRNAs) are recently reported to be potential surrogates for diagnosis of HBV-related HCC, such as deoxyribonuclease 1-like 3 (DNASE1L3), α-L-fucosidase (AFU), γ-glutamyl transferase isoenzyme II (GGT-II), glypican-3 (GPC3), hepatocyte growth factor (HGF) and miR-487b.…”