Diagnostic performance of serum PIVKA-II alone and in combination with AFP for hepatocellular carcinoma: A comparative retrospective study.

e15064 Background: Protein-Induced by Vitamin K Absence-II (PIVKA-II), being mechanistically linked to Hepatocellular carcinoma (HCC) pathogenesis, is considered a more specific biomarker than alpha-fetoprotein (AFP) and other diagnostic tools that often struggle to distinguish HCC from background liver pathology. This study evaluated the diagnostic performance of PIVKA-II alone and in combination with AFP, compared to AFP. Methods: AFP and PIVKA-II levels were measured in patients with biopsy-proven HCC, non-HCC liver malignancies, and benign liver diseases. Statistical analyses included non-parametric group comparisons, Spearman’s correlation, and receiver operating characteristic (ROC) analysis, optimal cut-offs, sensitivity, and specificity. Logistic regression was applied to assess combined diagnostic efficacy. Results: Among 128 participants (mean age:55.2±13.1y), AFP was assessed in 45 HCC, 51 non-HCC malignancies, and 32 benign cases, while PIVKA-II was measured in 20, 16, and 8 cases, respectively. Both biomarkers were significantly elevated in HCC compared with controls (P<0.001). PIVKA-II showed better diagnostic-performance (AUC=0.956) compared with AFP (AUC=0.815) for distinguishing HCC from non-HCC malignancies, though not statistically significant (P=0.222). PIVKA-II significantly outperformed AFP in differentiating HCC from benign liver disease (AUC=0.906 vs. 0.796; P=0.025). Optimal diagnostic thresholds were 105.8mAU/ml for PIVKA-II (sensitivity:95%, specificity:87.5%) and 33.6ng/ml for AFP (sensitivity:68.9%, specificity:86.3%). Combining AFP with PIVKA-II did not improve diagnostic accuracy beyond PIVKA-II alone, and no significant correlation was observed between AFP and PIVKA-II levels in HCC (r=0.371, P=0.108). Conclusions: PIVKA-II demonstrated superior diagnostic utility over AFP, particularly against benign liver disease. AFP did not improve diagnostic-accuracy, suggesting that PIVKA-II alone, with appropriately defined cut-off, may serve as a reliable biomarker. Summary of the diagnostic performance of serum AFP and PIVKA-II levels. Comparison Biomarker AUC (95% CI) Optimal Cut-off Sensitivity (95% CI) Specificity (95% CI) Z test (against AFP alone) HCC vs non-HCC liver malignancies AFP 0.815 (0.726, 0.903) 33.55 ng/ml 68.9% (54.26% to 80.55%) 86.3% (73.97% to 93.50%) - PIVKA-II 0.956 (0.894, 1.019) 105.80 mAU/ml 95.0% (88.7% to 98.4%) 87.5% (0.8530 to 0.8941) P=0.222 AFP+PIVKA-II combined 0.956 (0.894, 1.019) - 95.0% (88.7% to 98.4%) 87.5% (0.8530 to 0.8941) P=0.222 HCC vs benign liver conditions AFP 0.796 (0.695, 0.897) 28.00 ng/ml 68.9% (54.2% to 80.55%) 87.5%(71.32% to 95.64%) - PIVKA-II 0.906 (0.791, 1.021) 65.00 mAU/ml 100% (81.02% to 100%) 62.5%(30.38% to 86.51%) P=0.025 AFP+PIVKA-II combined 0.906 (0.791, 1.021) - 100% (81.02% to 100%) 62.5%(30.38% to 86.51%) P=0.025