Effect of AFP and PIVKA-II secretion status on prognosis of advanced hepatocellular carcinoma patients receiving TACE combined with systemic therapy

Few biomarkers can predict the effectiveness of transcatheter arterial chemoembolization (TACE) in combination with systemic therapies for patients with advanced hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic significance of changes in alpha-fetoprotein (AFP) and prothrombin induced by vitamin K absence-II (PIVKA-II), as well as their clinical utility in patients undergoing TACE combined with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs). This retrospective cohort study included advanced HCC patients who underwent TACE in combination with ICIs and TKIs at the Third Affiliated Hospital of Kunming Medical University between May 2021 and March 2024. Based on changes in serum AFP and PIVKA-II levels before and after treatment, patients were classified into four groups: AFP (↓) PIVKA-II (↓) (status 1), AFP (↓) PIVKA-II (↑) (status 2), AFP (↑) PIVKA-II (↓) (status 3), and AFP (↑) PIVKA-II (↑) (status 4). Kaplan-Meier analyses were conducted to compare the overall survival (OS) and progression-free survival (PFS) across the four groups. Univariate and multivariate Cox regression analyses were performed to identify potential prognostic factors for OS and PFS. A total of 215 patients were included in the study. Among them, 55.3% (119/215) achieved a complete or partial response. Significant differences in OS and PFS were observed among the various AFP-PIV status groups (P < 0.001). Patients with elevated AFP and PIVKA-II had the poorest OS and PFS compared to the other groups. Both elevated AFP alone and elevated PIVKA-II alone were associated with an increased risk of disease progression and death. In comparison, patients with reduced levels of both AFP and PIVKA-II showed a better prognosis. The AFP-PIV status was identified as an independent risk factor for OS and PFS in patients with advanced HCC. In summary, the findings of this study indicate that the AFP-PIV status serves as a significant prognostic marker, independently predicting OS and PFS in advanced HCC patients undergoing TACE in combination with systemic therapy.