Shared immune core genes in nonalcoholic steatohepatitis and primary biliary cholangitis

Nonalcoholic steatohepatitis (NASH) and primary biliary cholangitis (PBC) are chronic liver diseases characterized by immune dysregulation, but their shared mechanisms remain unclear. We integrated four GEO liver transcriptomic datasets to identify common differentially expressed genes, functional pathways, immune infiltration patterns, and candidate diagnostic genes. Differential expression, GO/KEGG and GSEA enrichment, protein-protein interaction network analysis, hub-gene screening, ROC analysis, bootstrap validation, and mouse-model experiments were performed. Twenty-five common differentially expressed genes were shared by NASH and PBC and were enriched in cytokine-mediated signaling, leukocyte chemotaxis, and inflammatory pathways. IL1RAP, IL1RN, CXCL2, CCL3, and CXCL9 showed favorable candidate diagnostic performance, with IL1RN displaying stable discrimination in both diseases. Immune infiltration analysis indicated abnormal M1 macrophage enrichment, and CXCL9 expression correlated positively with M1 macrophage infiltration. In NASH and PBC mouse models, histology and molecular assays supported increased expression of selected core genes. These findings suggest shared immune-related molecular features between NASH and PBC and provide candidate biomarkers for further clinical and mechanistic validation.