NX-PVKA levels before and after hepatectomy of hepatocellular carcinoma as predictors of patient survival: a preliminary evaluation of an improved assay for PIVKA-II.

Although the protein-induced vitamin K absence or antagonist-II (PIVKA-II) is used as a prognostic marker in hepatocellular carcinoma (HCC), a newly-improved assay, NX-PVKA (PIVKA-II measured using P-11 and P-16 antibodies) and NX-PVKA-R (ratio of PIVKA-II and NX-PVKA), are more accurate markers of PIVKA-II. We conducted a prospectively preliminary analysis of the relationship between NX-PVKA-R and clinicopathological parameters and prognosis in 22 patients with HCC who underwent hepatectomy and measured changes of this marker's levels after treatment. Median value of PIVKA-II (80 mAU/ml), NX-PVKA (60 mAU/ml), NX-PVKA-R (1.5) and NX-PVKA-D (difference of markers, 15 mAU/ml) were determined. Tumor relapse was observed in six patients, and the one year relapse-free survival rate was 88%. Correlation between PIVKA-II or alpha-fetoprotein levels and NX-PVKA, NX-PVKA-R or -D levels was significant (p<0.001). NX-PVKA-R was significantly correlated with tumor size (p<0.05). In patients who underwent pre-treatment before hepatectomy, PIVKA-II, NX-PVKA and NX-PVKA-R tended to be higher than in patients without pre-treatment, but this difference was not significant (p>0.10). For macroscopic findings, NX-PVKA-R for the confluent-nodular type was significantly higher than that for the simple-nodular type (p<0.05). The tumor-free survival rate in the group with a high NX-PVKA-R was significantly lower than that in the group with a low NX-PVKA-R group (p<0.05). In patients with tumor recurrence, postoperative NX-PVKA-R increased again. We conclude that a high value of NX-PVKA-R after hepatectomy for HCC reflects malignant potential and predicts early recurrence in patients with HCC.