LILRB4 Expression Is Associated with Macrophage Enrichment and Differential Survival in Hepatocellular Carcinoma

Background and aims The clinical and immune-cell context of leukocyte immunoglobulin-like receptor B4 (LILRB4) in hepatocellular carcinoma (HCC) remains incompletely characterized. Methods Public liver hepatocellular carcinoma (LIHC) resources were analyzed using survival, transcriptomic, functional enrichment, immune deconvolution, and single-cell analyses. Survival analyses included 373 patients for overall survival and 365 for disease-specific survival. Kaplan–Meier analyses compared two expression groups (high and low), defined using outcome-selected cutpoints obtained from maximally selected rank statistics. Continuous-expression Cox models provided complementary analyses. Results Higher LILRB4 expression was associated with shorter overall survival (OS) in an outcome-selected analysis ( n = 373; low-expression group, 250; high-expression group, 123; Cox hazard ratio [HR], 1.524; 95% confidence interval [CI], 1.074–2.162; log-rank p = 0.017). Continuous LILRB4 expression was associated with OS in univariable and adjusted Cox models (adjusted HR, 1.246; 95% CI, 1.010–1.537), whereas continuous expression was not significantly associated with disease-specific survival (HR, 1.137; 95% CI, 0.916–1.412). LILRB4 expression correlated with macrophage enrichment (Spearman r s = 0.755) and M2-like macrophage estimates from quanTIseq ( r s = 0.544) and CIBERSORT-ABS ( r s = 0.753). Single-cell resources localized LILRB4 mainly to monocyte/macrophage populations. Conclusion LILRB4 expression is associated with macrophage-enriched immune features and adverse survival patterns in LIHC. These findings identify LILRB4 as a candidate marker of the macrophage-rich HCC microenvironment that warrants further investigation of its prognostic and immunoregulatory relevance.