DefinePK

Abstract

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and ranks among the leading causes of cancer-related mortality worldwide. Early diagnosis remains a cornerstone in reducing its associated morbidity and mortality. Serum tumor markers such as alpha-fetoprotein (AFP), AFP-L3, Des-Gamma-Carboxy Prothrombin (DCP), and PIVKA-II are frequently used for screening and diagnostic purposes. However, their individual limitations in sensitivity and specificity, especially for early-stage disease, necessitate investigation into the diagnostic value of combined biomarker strategies.
Objective: To evaluate the diagnostic accuracy of combined serum tumor biomarkers for early detection of hepatocellular carcinoma.
Methods: A systematic review of literature published from January 2000 to March 2025 was conducted using PubMed and Google Scholar databases. A total of 20 peer-reviewed studies meeting inclusion criteria were analyzed. Data extraction focused on the diagnostic performance of serum biomarkers alone and in combination. Diagnostic accuracy was assessed using sensitivity, specificity, and area under the ROC curve (AUC).
Results: AFP alone demonstrated a sensitivity of 63.3% and specificity of 80.8%. PIVKA-II outperformed AFP with a sensitivity of 71% and specificity of 90%. AFP-L3 and GP73 showed higher diagnostic performance in small tumor detection, with GP73 achieving 72.0% sensitivity and 86.7% accuracy, and GPC3 offering 98.0% specificity. Combining AFP with AFU yielded the highest diagnostic values with 95% sensitivity and 100% specificity. The triplet panel of AFP, AFP-L3, and DCP achieved 88% sensitivity and 91% specificity. Biomarker combinations consistently outperformed individual tests in detecting early and all-stage HCC.
Conclusion: Single biomarkers like AFP are insufficient for early-stage HCC detection. Combining AFP with other markers such as PIVKA-II, AFP-L3, and DCP significantly enhances diagnostic accuracy. Adoption of multi-marker strategies may improve early detection and clinical outcomes in HCC.