Biochemical Predictors of Hepatocellular Carcinoma in Chronic Liver Disease: A Comparative Analysis of AFP and PIVKA-II
PIVKA-II versus AFP for HCC in chronic liver disease
Keywords:
Alpha-Fetoproteins, Biomarkers, Carcinoma, Hepatocellular, Liver Diseases, Prothrombin , TumorAbstract
Background: Hepatocellular carcinoma (HCC) ranks among the deadliest cancers, and a sizeable proportion of tumors go undetected by alpha-fetoprotein (AFP). Protein induced by vitamin K absence or antagonist-II (PIVKA-II) has emerged as a possible substitute. We set out to compare how well PIVKA-II and AFP identify HCC in people with chronic liver disease (CLD).
Methodology: We conducted a case-control study across two tertiary care hospitals in Hyderabad, Pakistan, between August 2025 and August 2026, enrolling 335 adults with CLD, of whom 119 had HCC and 216 did not. ELISA was used to measure serum PIVKA-II and AFP. For each marker we calculated sensitivity, specificity, predictive values and the area under the ROC curve (AUC), and the two AUCs were then compared using the DeLong test.
Results: Cases had a median PIVKA-II of 4500 (IQR 6050) pg/mL against 40 (IQR 21) pg/mL in controls, and a median AFP of 40 (IQR 270) ng/mL against 10 (IQR 12) ng/mL (p<0.001 for both). Using a cut-off of 76.5 pg/mL, PIVKA-II reached an AUC of 0.98 (95% CI: 0.97–0.99), with 98.3% sensitivity and 96.8% specificity. AFP, at 47 ng/mL, gave an AUC of 0.96 (95% CI: 0.93–0.98), with 95.0% sensitivity and 90.3% specificity (DeLong p=0.014). When an HCC prevalence of 6.73% was assumed, the positive predictive value was 68.6% for PIVKA-II and 41.3% for AFP.
Conclusion: PIVKA-II separated HCC from non-malignant CLD a little more accurately than AFP, chiefly because it produced fewer false positives. Until prospective surveillance data are available, it is better used together with AFP than in place of it.
DOI: https://doi.org/10.59564/amrj/04.04/007
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Copyright (c) 2026 Kumayl Abbas Meghji, Navaid Kazi, Farkhunda Nadeem, Salahuddin Shaikh, Muhammad Sadik Memon, Shahzad Rasheed
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