The combination of PIVKA-II and AFP improves the detection accuracy for HCC in HBV caucasian cirrhotics on long-term oral therapy

Background & Aims: Protein induced by vitamin K absence or antagonist-II (PIVKA-II) has been suggested as a serum biomarker for hepatocellular carcinoma (HCC) in Asian hepatitis B virus (HBV)-treated subjects but no studies tested it in Caucasian cirrhotics long-term nucleos(t)ide analogues (NUCs)-treated. We assessed the detection accuracy of PIVKA-II alone or in combination with alpha-foetoprotein (AFP) in patients under surveillance. Methods: This cross-sectional, single centre case-control study was conducted in 212 NUC-treated cirrhotics: 64 HCC and 148 HCC-free controls for 84 (60-107) months. PIVKA-II was determined by a CMIA immunoassay (Abbott; limit of quantification: 8.2 mAU/mL). Results: Protein induced by vitamin K absence or agonist II (PIVKA-II) and AFP levels were significantly higher in HCC patients [Barcelona Clinic Liver Cancer staging system stage 0/A in 91%, diameter 20 (6-50) mm] compared to controls: 109 (17-12 157) vs 31 (13-82) mAU/mL and 5 (1-1163) vs 2 (1-7) ng/mL (P <.001 for both markers), with a cut-off of 48 mAU/mL and 4.2 ng/mL by AUROC analysis. The PIVKA-II 82 mAU/mL and AFP 7 ng/mL cut-offs showed 100% specificity, with the former more sensitive (54% vs 42%), accurate (86% vs 83%), with higher negative predictive value (80% vs 76%) compared to AFP for HCC detection. PIVKA-II more frequently than AFP levels exceeded the cut-off 6-18 months before HCC diagnosis. Combining PIVKA-II with AFP increased sensitivity, accuracy and negative predictive values to 67%, 90% and 85%, preserving 100% specificity. PIVKA-II was associated with lesions >20 mm or neoplastic thrombosis. Conclusions: Combination of PIVKA-II and AFP increases the detection rate for HCC in NUC-treated HBV Caucasian cirrhotics, a potential new approach for surveillance.