In a retrospective cohort of patients with HBV-related cirrhosis from our institution (n = 147; 2022–2024), we identified nonlinear LDL-HCC thresholds via restricted cubic splines (RCS) and engineered a novel “A-index” (a composite score derived from principal component analysis (PCA) integrating alpha-fetoprotein (AFP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT)). This evidence concerns the gene AFP and hepatocellular carcinoma.