Measurement of protease activity using novel plasma biosensors can accurately detect hepatocellular carcinoma

0/A (n = 11), stage B (n = 16), stage C (n = 32) and stage D (n = 9), according to BCLC staging system.Results: Mean/median levels of AFP (10835/155 vs 129/4.3,p < 0.001) and PIVKA-II (11095/2660 vs 864/46, p < 0.001) were significantly higher in HCC group compared to control group.The AUROC curve and the best proposed cut-off value for HCC diagnosis were 82.9% (95%CI 76.3-89.4%)/13.4ng/ml and 78.4% (95%CI 71.1-85.8%)/654.49mAU/ml for AFP and PIVKA-II, respectively.The diagnostic accuracy of PIVKA-II among BCLC-C stage HCC patients was the best observed (AUROC = 88.1%,best proposed cut-off value = 655 mAU/ml).Excluding HCC patients with AFP levels above 400 ng/ml, the diagnostic accuracy of PIVKA-II in HCC continued to be significant (best proposed cut-off value 1089.53 mAU/ml) but the AUROC curve (72.1%) for HCC diagnosis was further reduced.It is worth mentioning that extremely high values of PIVKA-II (like those that are noticed in advanced HCC) were observed in 3 cirrhotic patients without HCC following treatment with acenocoumarol (the 2 of them) or having very low levels of vitamin K because of prolonged cholestasis due to sclerosing cholangitis (the third one).In these cases the diagnostic accuracy of the biomarker may be significantly affected.Conclusion: Both biomarkers showed moderate accuracy for detecting HCC in patients with liver cirrhosis, when they were used separately.The diagnostic accuracy of PIVKA-II in patients with relatively low AFP levels (<400 ng/ml) remained at the same level.