Diagnostic Performance of AFP, PIVKA-II, and the ASAP Score for Distinguishing Hepatocellular Carcinoma With and Without Portal Vein Tumor Thrombus: A Retrospective Single-Center Study From Pakistan.

BACKGROUND: Portal vein tumor thrombus (PVTT) is an important manifestation of advanced hepatocellular carcinoma (HCC). Serum alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) are established biomarkers associated with tumor burden, vascular invasion, and disease progression in HCC. However, their utility in distinguishing HCC patients with PVTT from those without PVTT remains poorly characterized in the Pakistani population. METHODS: This retrospective single-center study included 100 consecutive, newly diagnosed HCC patients: 46 with PVTT and 54 without PVTT. A separate group of 55 cancer-free controls was included solely for a secondary exploratory HCC-versus-control analysis. Diagnostic performance of AFP, PIVKA-II, and the Age-Sex-AFP-PIVKA-II (ASAP) score was evaluated using two-sided Mann-Whitney U tests, receiver operating characteristic (ROC) curve analysis, Youden index cutoffs, Spearman correlation, and multivariable logistic regression. ASAP values were calculated consistently from the raw variables before analysis. RESULTS: AFP and PIVKA-II were significantly higher in patients with PVTT than those without PVTT (AFP: p<0.001; PIVKA-II: p=0.030). AFP demonstrated the highest overall discriminatory performance for identifying PVTT, with an area under the ROC curve (AUROC) of 0.740 (95% confidence interval (CI): 0.642-0.837), achieving 78.3% sensitivity and 64.8% specificity at a cutoff value of 39.7 ng/mL. PIVKA-II yielded an AUROC of 0.627 (95% CI: 0.517-0.736), demonstrating high sensitivity (95.7%) but limited specificity (33.3%). The ASAP score achieved an AUROC of 0.688 (95% CI: 0.584-0.791) and did not outperform AFP. In multivariable logistic regression, natural logarithm-transformed (ln-transformed) AFP remained independently associated with PVTT (odds ratio: 1.249; 95% CI: 1.080-1.445; p=0.003), whereas ln-transformed PIVKA-II did not. CONCLUSION: Among patients with established HCC, AFP demonstrated better overall discriminatory performance than PIVKA-II for identifying PVTT, whereas PIVKA-II provided high sensitivity but limited specificity. The ASAP score did not improve diagnostic performance beyond AFP alone. These biomarkers may complement, but should not replace, contrast-enhanced imaging for the assessment of PVTT. Larger prospective multicenter studies are required to validate these findings before routine clinical implementation.