α-Fetoprotein, α-Fetoprotein-L3, and Des-γ-Carboxy Prothrombin Stratify Hepatocellular Carcinoma Treatment Response and Progression Risk

Abstract

Background & AimsAssessing aggressive biology at early-stage HCC diagnosis remains challenging. Alpha-fetoprotein (AFP) is the only clinical biomarker of aggressive HCC. In this study, AFP, Lens culinaris agglutinin-reactive AFP (AFP-L3), and des-γ-carboxy prothrombin (DCP) were measured at diagnosis prior to transplant evaluation and first cycle liver-directed therapy (LDT). MethodsThe prospective cohort included 207 patients who received LDT as a bridge/downstage to transplant or definitive treatment plan between 2016 and 2022. Plasma AFP, AFP-L3, and DCP levels were measured at diagnosis and analyzed with other factors associated with treatment response and time-to-progression (TTP). ResultsBiomarker phenotyping revealed 41% were triple negative, 30% expressed multiple biomarkers, and 12% express all three biomarkers. The biomarker profile was associated with target/overall response rate and TTP (P < 0.001). Profiling stratified 1-year progression risk in non-transplant candidates, driven by co-expression of AFP and DCP in multivariate analysis controlling for tumor burden and staging. ConclusionThe biomarker panel at diagnosis established prognosis for LDT response and stratified 1-year HCC progression risk. AFP, AFP-L3, and DCP profiling isolated aggressive HCC biology at diagnosis and may have important implications in post-LDT surveillance and transplant wait time.