Comparative single-cell landscape of immune cells in human livers affected HBV and non-viral cirrhosis

<h4>Background</h4>Cirrhosis, particularly HBV-induced, poses a significant global health burden. This study compares immune cell landscapes in HBV and non-viral cirrhosis using single-cell RNA sequencing (scRNA-seq) to elucidate distinct immune mechanisms driving disease progression.<h4>Methods</h4>Liver tissues from HBV cirrhosis patients and healthy controls were analyzed via scRNA-seq. Public single-cell and spatial transcriptomics data were integrated to map immune cell populations. Computational analyses included differential expression, pathway enrichment (KEGG/GO), and cell-cell communication (CellChat).<h4>Results</h4>HBV cirrhosis exhibited expanded Macrophage-PLCG2 (anti-inflammatory) and CD8 + T-FABP5 subsets, while Macrophage-CD5L, CD4 + T-ANXA1, CD4 + T-CCR6, and NK-FCER1G were reduced. Pathway analysis linked Macrophage-PLCG2 to Rap1 signaling, whereas Macrophage-CD5L associated with lysosomal pathways. Spatial analysis revealed myeloid-T cell colocalization in HBV cirrhosis. Enhanced HLA-E/KLRK1 signaling between myeloid and NK cells was identified in HBV cases (<i>p</i> < 0.05).<h4>Conclusion</h4>This study delineates immune cell heterogeneity between HBV and non-viral cirrhosis, highlighting potential therapeutic targets like Macrophage-PLCG2 and CD8 + T-FABP5. Findings underscore the role of immune dysregulation in HBV cirrhosis progression.