Diagnostic value of serum PIVKA-II levels for BCLC early hepatocellular carcinoma and correlation with HBV DNA

Abstract

Background: It is reported that prothrombin induced by vitamin K absence-II (PIVKA-II) has a better performance of diagnosis for HCC, and has also been known to be an independent risk factor for vascular invasion. Few studies study the relationship between PIVKA-II and HBV DNA.

Objective: To determine the clinical value of serum Prothrombin induced by vitamin K absence-II (PIVKA-II) in early hepatocellular carcinoma (HCC), and to explore its relationship with vascular invasion and HBV DNA.

Methods: In a Chinese cohort, we conducted a case-control study to compare the performances of a-fetoprotein (AFP) and PIVKA-II serum levels for diagnosis of HCC and early HCC. Fifty one healthy controls, 37 chronic hepatitis patients, 43 cirrhotic patients and 143 HCC cases of which 48 (33.57%) had early stage HCC (n= 19 very early, n= 29 early) were enrolled. We explored the correlation between PIVKA-II serum level and several pathological features such as vascular invasion. The serum levels of and AFP were measured by chemiluminescence assay (CLIA) and electrochemiluminescence assay (ECLA).

Results: The serum levels of both PIVKA-II and AFP in HCC group were higher than that in chronic hepatitis, cirrhosis and healthy control groups. The sensitivity, specificity, positive predictive value, negative predictive value and kappa of PIVKA-II were higher than AFP in the diagnosis of HCC. Serum PIVKA-II level was correlated with tumor size, tumor cell differentiation and BCLC staging (P< 0.05). For the diagnosis of early HCC, the combination of PIVKA-II (AUC 0.812; 95% CI, 0.702-0.894) and AFP (0.797; 95% CI, 0.686-0.883) slightly improve the diagnostic performance for early HCC(AUC 0.849; 95% CI, 0.745-0.923). PIVKA-II > 166 mAU/ml is an independent risk factor for vascular invasion. The serum HBV DNA level in cirrhosis and HCC patients was significantly higher than in chronic hepatitis patients. We detected a negative association between serum PIVKA-II and serum HBV DNA levels.

Conclusions: PIVKA-II was more efficient than AFP for the diagnosis of early HCC and has no correlation with serum HBV DNA levels.

Keywords: HBV DNA load; Hepatocellular carcinoma; alpha fetoprotein; prothrombin induced by vitamin K absence-II; vascular invasion.