Inflammation drives pathogenesis of early intestinal failure-associated liver disease
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View abstract on PubMed
Summary
This summary is machine-generated.Parenteral nutrition (PN) can cause liver disease in infants. This study used a piglet model to find that inflammation drives early liver injury, suggesting anti-inflammatory drugs may be effective treatments for intestinal failure-associated liver disease (IFALD).
Area Of Science
- Hepatology
- Neonatal Medicine
- Molecular Biology
Background
- Long-term parenteral nutrition (PN) is crucial for patients with intestinal failure but can lead to intestinal failure-associated liver disease (IFALD).
- The early mechanisms driving IFALD pathogenesis remain unclear, and effective treatments are limited.
- Understanding the early molecular changes in IFALD is essential for developing targeted therapies.
Purpose Of The Study
- To investigate the early transcriptomic changes in the liver of a large animal model of IFALD.
- To identify potential therapeutic targets and mechanistic insights into IFALD development.
- To explore potential upstream regulators that could reverse PN-induced gene dysregulation.
Main Methods
- Preterm Yorkshire piglets were administered PN or fed a sow-milk replacer for 14 days.
- Biochemical markers of cholestasis were measured.
- RNA-sequencing (RNA-Seq) of liver tissue was performed, followed by Ingenuity Pathway Analysis (IPA).
Main Results
- PN-fed piglets developed significant biochemical cholestasis compared to controls.
- Transcriptomic analysis revealed 747 differentially expressed genes in PN-fed piglets.
- IPA identified activated inflammatory pathways and inhibited cell cycle progression.
- Potential therapeutics, including infliximab, glucocorticoids, statins, and obeticholic acid, were predicted as upstream regulators.
Conclusions
- Early IFALD in neonates may be driven by inflammation in an immature liver.
- Targeting inflammatory responses in the liver presents a promising therapeutic strategy for IFALD.
- Further investigation of identified therapeutics is warranted to treat PN-induced liver injury.
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