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

OBJECTIVES

To identify molecular biomarkers associated with chronic liver failure (CLF) progression to acute-on-chronic liver failure (ACLF).

METHODS

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.

RESULTS

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.

CONCLUSIONS

Bile acid metabolism dysregulation and associated hub genes may contribute to CLF severity progression, warranting validation in larger cohorts.