Utility of Biomarker Panels in the Surveillance and Monitoring of Hepatocellular Carcinoma: Consensus Statements from an International Delphi Panel

Abstract

Hepatocellular carcinoma (HCC) surveillance is recommended using a combination of abdominal ultrasound plus alpha-fetoprotein (AFP) in patients with chronic hepatitis B or cirrhosis from any etiology. However, this strategy is limited by suboptimal sensitivity for early-stage HCC, particularly in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease. Phase 2 and phase 3 biomarker studies have reported the promise of novel blood-based biomarkers, including AFP, des-gamma-carboxy prothrombin, and lens culinaris agglutinin-reactive AFP (AFP-L3). Biomarker panels, such as the GALAD score, GAAD, and ASAP combine these biomarkers plus age and gender into biomarker panels. A panel of 10 experts from Asia and the USA convened to discuss the clinical utility of these biomarkers for detecting early-stage HCC. The experts agreed that biomarker panels have shown higher sensitivity than each individual biomarker and showed promise for early-stage HCC detection, particularly in those with a high proportion of patients with obesity and MASLD and geographies with insufficient access to high-quality ultrasound. However, biomarkers require prospective validation in clinical utility trials demonstrating net benefit in patients with cirrhosis, and implementation may face challenges including widespread access to testing, broader insurance coverage, and improving awareness among physicians and patients.