Integrated analysis of transcriptome and metabolome reveals key metabolites-related genes in chronic liver failure

To identify molecular biomarkers associated with chronic liver failure (CLF) progression to acute-on-chronic liver failure (ACLF). RNA-seq data from 8 CLF patients—stratified into high-severity (G, ACLF with total bilirubin ≥171 μmol/L) and low-severity (L, stable CLF with total bilirubin <171 μmol/L) groups—along with 4 healthy controls were analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to identify disease-associated gene modules. A total of 3112 differentially expressed genes (DEGs) were identified, with KEGG analysis showing enrichment in innate immune pathways. Metabolomic profiling revealed 63 differentially expressed metabolites (DEMs), with four bile acids—Glycochenodeoxycholic acid, Glycocholic acid, Glycodeoxycholic acid, and Lithocholic acid—identified as key metabolites in bile acid biosynthesis pathways. Strong negative correlations were observed between these hydrophobic bile acids and 33 hub genes. Bile acid metabolism dysregulation and associated hub genes may contribute to CLF severity progression, warranting validation in larger cohorts. Integrated analysis of transcriptome and metabolome reveals key metabolites-related genes in chronic liver failure. • 33 hub genes were linked to the severity of chronic liver failure (CLF). • DEGs were most enriched in Influenza A and Hepatitis C pathways. • Four specific bile acids were correlated with CLF progression. • Bile acid biosynthesis is a key process contributing to CLF severity.