Diagnostic value of PIVKA-II and alpha-fetoprotein in hepatitis B virus-associated hepatocellular carcinoma

Abstract

Aim: To determine the cutoff values and to compare the diagnostic role of alpha-fetoprotein (AFP) and prothrombin induced by vitamin K absence-II (PIVKA-II) in chronic hepatitis B (CHB).

Methods: A total of 1255 patients with CHB, including 157 patients with hepatocellular carcinoma (HCC), 879 with non-cirrhotic CHB and 219 with cirrhosis without HCC, were retrospectively enrolled. The areas under the receiver operating characteristic (AUROC) curves of PIVKA-II, AFP and their combination were calculated and compared.

Results: The optimal cutoff values for PIVKA-II and AFP were 40 mAU/mL and 10 ng/mL, respectively, for the differentiation of HCC from nonmalignant CHB. The sensitivity and specificity were 73.9% and 89.7%, respectively, for PIVKA-II and 67.5% and 90.3% for AFP, respectively. The AUROC curves of both PIVKA-II and AFP were not significantly different (0.854 vs 0.853, P = 0.965) for the differentiation of HCC from nonmalignant CHB, whereas the AUROC of PIVKA-II was significantly better than that of AFP in patients with cirrhosis (0.870 vs 0.812, P = 0.042). When PIVKA-II and AFP were combined, the diagnostic power improved significantly compared to either AFP or PIVKA-II alone for the differentiation of HCC from nonmalignant CHB (P < 0.05), especially when cirrhosis was present (P < 0.05).

Conclusion: Serum PIVKA-II might be a better tumor marker than AFP, and its combination with AFP may enhance the early detection of HCC in patients with CHB.

Keywords: Alpha-fetoprotein; Hepatitis B virus; Hepatocellular carcinoma; Prothrombin induced by vitamin K absence-II.

Figures

Figure 1

Receiver operating characteristic curves comparing prothrombin induced by vitamin K absence-II, alpha-fetoprotein and a combination of alpha-fetoprotein and prothrombin induced by vitamin K absence-II in patients with hepatocellular carcinoma vs those with nonmalignant chronic hepatitis B. The AUROC curves for PIVKA-II, AFP, and Combination are indicated in the inset. P = 0.965 for AFP vs PIVKA-II, P < 0.001 for combination vs PIVKA-II and P = 0.037 for combination vs AFP. PIVKA-II: Prothrombin induced by vitamin K absence-II; HCC: Hepatocellular carcinoma; AFP: Alpha-fetoprotein.

Figure 2

Receiver operating characteristic curves comparing prothrombin induced by vitamin K absence-II, alpha-fetoprotein and a combination of alpha-fetoprotein and prothrombin induced by vitamin K absence-II in patients with hepatocellular carcinoma vs those with liver cirrhosis. The AUROC curves for PIVKA-II, AFP, and Combination are indicated in the inset. P = 0.042 for AFP vs PIVKA-II, P = 0.001 for combination vs PIVKA-II and P < 0.001 for combination vs AFP. PIVKA-II: Prothrombin induced by vitamin K absence-II; HCC: Hepatocellular carcinoma; AFP: Alpha-fetoprotein.