Significance of PIVKA-II levels for predicting microvascular invasion and tumor cell proliferation in Chinese patients with hepatitis B virus-associated hepatocellular carcinoma

Oncol Lett. 2018 Jun;15(6):8396-8404. doi: 10.3892/ol.2018.8375. Epub 2018 Mar 29.

Abstract

The present study aimed to determine the levels of prothrombin induced by vitamin K absence-II (PIVKA-II) according to the Barcelona Clinic Liver Cancer (BCLC) staging system, to develop an appropriate strategy for managing hepatocellular carcinoma (HCC), particularly early HCC, and to investigate the value of PIVKA-II for predicting prognosis-associated pathological parameters. Clinical information of 117 patients with hepatitis B-associated HCC was retrospectively collected. Preoperative serum PIVKA-II and α-fetoprotein (AFP) levels were measured using a chemiluminescence method. The efficiency of PIVKA-II levels for predicting pathological parameters was evaluated using step-wise logistic regression. The receiver operator characteristic curve was used to evaluate the predictive performance of PIVKA-II levels. It was demonstrated that except for the difference between stages B and C HCC (P=0.923), serum PIVKA-II levels significantly increased according to BCLC stage (P<0.050), however AFP levels did not. In early HCC (stage 0+A), the correlation between PIVKA-II and AFP levels (dual-positive, 64.70% in stage 0; 46.97% in stage A) was relatively weak (r=0.410). PIVKA-II >40 mAU/ml was an independent predictor of microvascular invasion [hazard ratio (HR), 3.77; 95% confidence interval (CI), 1.31-10.88; P=0.014; and high Ki67 expression in situ (HR, 2.99; 95% CI, 1.19-7.52; P=0.020). Combined analysis of PIVKA and AFP levels may contribute to an effective strategy for the management of patients with early HCC, as high PIVKA-II levels indicated a more aggressive tumor phenotype. Further investigation of PIVKA-II levels may provide novel insights into the mechanism underlying the metastasis of HCC cells and facilitate the development of novel therapeutic strategies for HCC.

Keywords: Ki67; PIVKA-II; hepatocellular carcinoma; microvascular invasion; proliferation.