Specifically, functional validation of our core signatures—particularly the 125 pan-etiology DEGs and 220 HCV-specific DEGs—would require: (1) multi-omics profiling (RNA-seq/proteomics) in etiology-stratified patient cohorts to confirm cross-platform consistency (2) CRISPR-based screens in HBV+ (e.g., HepG2.2.15), and HCV+ (e.g., JFH-1-infected Huh7) HCC cell lines to establish causality for hub genes like CDK1 and ABCA8, and (3) longitudinal studies in preclinical models that replicate the cirrhosis-to-HCC transition (6–18 months). Here, CDK1 is linked to Cirrhosis.