Diagnostic Accuracy of Serum Protein Induced by Vitamin K Absence (PIVKA-II), Serum A-fetoprotein and Their Combination for Hepatocellular Carcinoma Among Caucasian Cirrhotic Patients with Diagnostic or Non-diagnostic Serum A-fetoprotein Levels

Aim: The aim of our study was to evaluate the accuracy of serum biomarkers (AFP/PIVKA-II) and their combination in HCC diagnosis among Caucasian cirrhotic patients.

Methods: Serum AFP/PIVKA-II levels were evaluated in 218 cirrhotics (163 males, 118 CTP-A, 66 ALBI-I, 111 with varices, 63 with diabetes) with (n = 90) or without (n = 128) HCC. Patients with HCC were categorized to BCLC Stage 0/A (n = 12), B (n = 21), C (n = 48), and D (n = 9).

Results: The two groups were comparable for all baseline parameters except for age, platelets, and diabetes presence. Median levels of AFP (239.1 vs. 4.0 ng/mL) and PIVKA-II (4082.7 vs. 45.8 mAU/mL) were both significantly higher in HCC group compared to controls (p < 0.001). AUROC and cutoff value for HCC diagnosis were 88%/12.35 ng/mL (AFP) and 84.4%/677.13 mAU/mL (PIVKA-II), whereas their combination showed better diagnostic accuracy (AUROC = 90.2%). The diagnostic accuracy of each biomarker separately was moderate or good in BCLC-0/A/B and was excellent only for BCLC-C patients (AFP: AUROC = 94.3%, cutoff = 12.35 ng/mL and PIVKA-II: 91.3%, 253.51 mAU/mL) whereas their combination presented quite acceptable results in BCLC-B (AUROC = 92.4%) and BCLC-C (AUROC = 95.7%). Excluding HCC patients with high AFP (above 400 ng/mL), the diagnostic accuracy of each biomarker separately and their combination was moderate/good in all groups, except for their combination in BCLC-C (AUROC = 90.5%).

Conclusions: Each biomarker separately showed acceptable accuracy for detecting HCC in cirrhotic patients and excellent for those in BCLC-C stage. The combination of the biomarkers presented excellent results in BCLC-B/C patients. The diagnostic accuracy of PIVKA-II and the combination of the two biomarkers in patients expressing low/non-diagnostic AFP levels was good in BCLC-B and excellent in BCLC-C patients.