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

Núñez K, Schneider M, Sandow T, Gimenez J, Hibino M, Fort D, Cohen A, Thevenot P

Background and Aims Assessing aggressive biology at early-stage hepatocellular carcinoma (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-gamma-carboxy prothrombin (DCP) were measured at diagnosis prior to transplant evaluation and first cycle liver-directed therapy (LDT). Methods The 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. Results Biomarker phenotyping revealed 41% were triple negative, 30% expressed multiple biomarkers, and 12% express all 3 biomarkers. The biomarker profile was associated with target/overall response rate and time-to-progression (P < .001). Profiling stratified 1-year progression risk in nontransplant candidates, driven by coexpression of AFP and DCP in multivariate analysis controlling for tumor burden and staging. Conclusion The 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.

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