OBJECTIVES: This study analyzed potential key genes involved in the mechanism of acute liver injury induced by sepsis through bioinformatics techniques, aiming to provide novel insights for the identification of early-stage sepsis-induced acute liver injury and its diagnosis. METHODS: Gene chip data sets containing samples from acute liver injury induced by sepsis and control groups (GSE22009 and GSE60088) were selected from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) with |log fold change| >
1 and RESULTS: A total of 646 upregulated DEGs were determined in GSE22009 and 146 in GSE60088. A Venn diagram was used to find the intersection of the upregulated DEGs between the two data sets, and 67 DEGs associated with sepsis-mediated acute liver damage were obtained. Enrichment analysis from the KEGG pathway showed that DEG upregulation was primarily associated with various pathways: TNF, NF-κB, IL-17, ferroptosis, mTOR, and JAK-STAT signaling pathways. DEGs resulted in three clusters and 15 candidate genes, as revealed by the PPI network and module analyses. Intersection with sepsis-induced acute liver injury-related genes in the CTD resulted in the identification of three significant differentially co-expressed genes: CONCLUSION: The key genes identified and related signaling pathways provided insights into the molecular mechanisms of sepsis-induced acute liver injury. In vivo studies revealed the overexpression of