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Intrahepatic Transcriptomics Differentiate Advanced Fibrosis and Clinical Outcomes in Adults With Fontan Circulation
Katia Bravo-Jaimes1, Xiuju Wu2, Leigh C Reardon3
1Department of Cardiovascular Medicine, Mayo Clinic, Jacksonville, Florida, USA; Ahmanson/UCLA Adult Congenital Heart Disease Center, University of California, Los Angeles, California, USA.
Journal of the American College of Cardiology
|February 14, 2024
Summary
Fontan-associated liver disease (FALD) shows distinct molecular signatures in advanced fibrosis and adverse outcomes. Key upregulated genes indicate inflammation, congestion, and angiogenesis, offering insights into FALD progression.
Area of Science:
- Cardiovascular Medicine
- Hepatology
- Molecular Biology
Background:
- Fontan-associated liver disease (FALD) molecular mechanisms are poorly understood.
- FALD impacts patients with Fontan circulation, a complex congenital heart defect repair.
- Identifying transcriptomic differences is crucial for understanding FALD progression.
Purpose of the Study:
- To investigate intrahepatic gene expression differences in FALD patients.
- To correlate transcriptomic profiles with liver fibrosis severity and clinical outcomes.
- To elucidate molecular pathways involved in FALD pathogenesis.
Main Methods:
- Retrospective cohort study of 106 adults with Fontan circulation.
- Analysis of liver biopsy samples for differential gene expression (RNA sequencing).
- Correlation of gene expression with fibrosis stage, clinical data, and composite clinical outcome (CCO).
Main Results:
- Advanced fibrosis and CCO were associated with distinct gene expression profiles.
- 136 upregulated genes were common in advanced fibrosis and CCO groups.
- Enriched pathways included cytokine response, oxidative stress, VEGFR2 signaling, TGF-β signaling, and vasculature development.
Conclusions:
- FALD with advanced fibrosis or CCO shows upregulated genes linked to inflammation, congestion, and angiogenesis.
- These findings highlight key molecular pathways in FALD progression.
- Transcriptomic analysis provides novel insights into FALD pathophysiology.
