The prognostic significance and clinical application of Mac-2 binding protein glycosylation Isomer, Lectin-Reactive α-Fetoprotein Fraction, and protein induced by vitamin K Absence-II in resectable hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortalities. Although hepatic resection provides favorable outcomes for resectable HCC (R-HCC), its recurrence rate remains high. This study aimed to evaluate the prognostic significance and clinical applicability of the Mac-2 binding protein glycosylation isomer (M2BPGi), lectin-reactive α-fetoprotein fraction (AFP-L3), and protein induced by vitamin K absence-II (PIVKA-II), together with tumor characteristics, in patients with R-HCC who underwent hepatic resection. METHODS: We retrospectively analyzed 250 R-HCC patients who underwent hepatic resection between 2015 and 2025 at a single institution. Preoperative biomarkers including M2BPGi, AFP-L3, and PIVKA-II, were evaluated. The primary endpoint was the disease-free survival (DFS). RESULTS: A multivariate analysis identified M2BPGi ≥ 1.0 (hazard ratio (HR) 2.01, p < 0.001), AFP-L3 ≥ 15% (HR, 1.84, p = 0.03), and PIVKA-II ≥ 500 mAU/mL (HR 2.44, p < 0.001) were independent predictors of recurrence. A scoring system based on the number of positive biomarkers significantly stratified DFS (P < 0.001). Patients positive for all three markers had the poorest prognoses. CONCLUSIONS: M2BPGi, AFP-L3, and PIVKA-II are independent risk factors for recurrent HCC. A simple biomarker-based scoring system offers practical guidance to hepatobiliary surgeons for tailoring postoperative surveillance and evaluating candidates for adjuvant strategies.