Performance of Serum Biomarkers (AFP, DCP) Combined with Imaging Modalities in Early HCC Detection: A Prospective Study

Background Early detection of hepatocellular carcinoma (HCC) is crucial for curative management, yet current surveillance methods remain suboptimal, particularly in high-burden, resource-limited settings. While serum alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) have shown promise as biomarkers, their combined value with imaging modalities for early HCC detection requires validation in real-world, South Asian populations. Methods We conducted a prospective, observational cohort study at Hayatabad Medical Complex, Peshawar, from May 2024 to May 2025. Adults with chronic liver disease, free of known HCC at enrollment, underwent six-monthly assessments with serum AFP and DCP, ultrasonography, and, where indicated, multiphase MRI. Diagnostic performance metrics—sensitivity, specificity, positive and negative predictive values (PPV, NPV), and area under the receiver operating characteristic curve (AUC)—were calculated for each modality and their combinations. Early HCC was defined by international criteria. Analyses were performed using R (v4.3.1), with missing data addressed by multiple imputation. Results Of 192 participants (median age 53 years, 61.5% male), 21 developed incident early-stage HCC (10.9%; 95% CI 7.2–16.1%) during follow-up. Sensitivity for early HCC detection was 61.9% (AFP alone), 71.4% (DCP alone), 57.1% (ultrasound alone), and 85.7% for combined AFP+DCP. The AFP+DCP+ultrasound strategy yielded the highest sensitivity (90.5%; 95% CI 69.6–98.8), with an AUC of 0.90. MRI confirmed all cases with indeterminate initial findings. No significant differences were observed in diagnostic accuracy by age, sex, or CLD etiology. No major adverse events were reported. Conclusions In this real-world South Asian cohort, the combination of serum AFP and DCP with ultrasonography substantially improved early HCC detection compared to any single modality. These findings support integration of multimodal surveillance strategies—including DCP—into local and regional screening programs, with potential to inform policy and reduce liver cancer mortality in high-risk populations.