Biomarkers + USG and HCC Detection: Gastroenterology | March 2026

Introduction: The Biomarkers Used for HCC Surveillance

Ultrasound (US) is the backbone of hepatocellular carcinoma (HCC) surveillance, but its sensitivity for early-stage HCC is imperfect. Blood-based biomarkers are attractive adjuncts because they are easy to repeat and potentially detect tumors missed by US. The commonly studied serum biomarkers include:

AFP (alpha-fetoprotein): classic HCC marker, but limited specificity in active liver inflammation.

AFP-L3: lectin-reactive AFP fraction, thought to reflect more malignant AFP isoforms.

DCP (des-gamma-carboxy prothrombin/PIVKA-II): associated with HCC biology and vascular invasion in some cohorts.

This trial tested whether combining these biomarkers with US improves early-stage detection.

Summary

In this randomized controlled trial, 1208 high-risk adults (cirrhosis or high-risk HBV) were assigned to biannual surveillance with US alone or US plus serum biomarkers (AFP, AFP-L3, DCP). Biomarker thresholds triggering diagnostic imaging were AFP >100 ng/mL, AFP-L3 >10%, or DCP >2 ng/mL. Over follow-up, 35 HCCs occurred in the US-only arm and 27 in the combined arm, with no difference in early-stage HCC detection between strategies (HR 0.81; P=.45). Late-stage cancers were similar in both groups. Within the biomarker arm, AFP-L3 alone performed similarly to using all three biomarkers combined. Overall, adding AFP/AFP-L3/DCP to ultrasound did not improve early HCC detection in this study, and the trial was not powered to prove benefit for biomarkers beyond US ± AFP.