Prognostic Values of α-fetoprotein and Protein Induced by Vitamin K Absence or Antagonist-II in Hepatitis B Virus-related Hepatocellular Carcinoma : A Prospective Study

Background/Aim: Alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-Il (PIVKA-II) are most widely used tumor markers in detecting hepatocellular carcinoma (HCC). Recently, there have been some studies about them as prognostic markers in hepatitis C virus-associated HCC. However, prognostic values of AFP and PIVKA-II remain clarified in hepatitis B virus (HBV)-associated HCC. This study was aimed to evaluate the prognostic values of AFP and PIVKA-II in HBV-associated HCC. Methods: Patients (n = 126) were divided into 4 groups according to median levels of AFP and PIVKA-II (L; low/low, A; high/low, P; low/high, H; high/high) at diagnosis. Clinical characteristics and survival were compared among the groups, and Cox regression analysis was performed to find independent factors for survival. Results: Baseline host and viral factors were not significantly different among the 4 groups. High PIVKA-II groups (P and H) had more aggressive tumor characteristics (larger size of tumors, higher number of tumors, frequent portal vein thrombosis, P < 0.05) and much shorter median survival time than low PIVKA-II groups (L and A) (P < 0.05). In multivariate analysis, high PIVKA-II level was an independent predictor for survival (risk ration: 2.377, 95% confidence interval: 1.359-4.157, P = 0.002) together with Child-Pugh score, advanced TMN stages, and treatment modality. Even after excluding 33 patients who had Child-Pugh class C and advanced tumor stages (tumor-nodesmetastasis stage III-IV) at diagnosis, high PIVKA-II level was still an independent predictor for survival (risk ration: 4.258, 95% confidence interval: 2.418-8.445, P < 0.001). Conclusions: Serum PIVKA-II level, not serum AFP, was a valuable independent prognostic factor in HBV-related HCC.