Conserved hepatic RNA signatures across multiple cohorts reveal novel mechanistic clues for advanced fibrosis in human MASLD
Jessica L. Maiers, Tiebing Liang, Tingbo Guo, Sha Cao, Prakash Ramachandran, Teresa J. Raba, Stefano Romeo, Oveis Jamialahmadi, Arman Shahrisa Etu, Naga ChalasaniBackground:
Fibrosis development in patients with metabolic dysfunction–associated steatotic liver disease (MASLD) is a key indicator of disease progression and clinical outcome. Bulk and single-cell transcriptomics on human tissue have advanced understanding of fibrosis progression, but interstudy heterogeneity and limited sample size hinder the identification of consistent and targetable fibrogenic mechanisms.
Methods:
To identify conserved fibrogenic mechanisms, we performed a comprehensive meta-analysis of hepatic transcriptomic data with fibrosis stage characterized from ~1000 patients with MASLD.
Results:
Our meta-analysis revealed 846 differentially regulated genes associated with fibrosis progression (F3–4 vs. F0–1). Pathway analysis showed that these genes are involved in matrix organization (
Conclusions:
We identified conserved transcriptomic changes and gene networks in patients with advanced fibrosis, as well as putative ligand–receptor interactions that facilitate cell–cell interactions that drive fibrosis. These findings will inform mechanistic studies and the development of anti-fibrotic therapies.