New Insights Into Intestinal Failure-Associated Liver Disease in Children
Racha T Khalaf1, Ronald J Sokol1
1Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Digestive Health Institute, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO.
Insights
Intestinal failure-associated liver disease (IFALD) stems from parenteral nutrition (PN) and gut-liver axis issues. Modifying lipid emulsions offers new therapeutic strategies to prevent and treat IFALD.
Area of Science:
- Hepatology
- Gastroenterology
- Pediatric Gastroenterology
Background:
- Intestinal failure-associated liver disease (IFALD) is a frequent complication in patients receiving long-term parenteral nutrition (PN).
- The pathogenesis involves complex interactions within the gut-liver axis, including dysbiosis, altered intestinal permeability, and hepatic innate immune activation.
- Sepsis episodes further exacerbate the risk and progression of IFALD.
Purpose of the Study:
- To review current understanding of IFALD pathogenesis, focusing on molecular and cellular mechanisms.
- To discuss advancements in therapeutic and preventative strategies for IFALD.
- To highlight challenges in managing patients with IFALD.
Main Methods:
- Literature review of recent research on IFALD.
- Analysis of molecular and cellular pathways involved in IFALD development.
- Evaluation of novel therapeutic interventions and their clinical impact.
Main Results:
- PN lipid emulsions, particularly plant sterols, contribute to IFALD by activating hepatic immune responses.
- Gut dysbiosis and impaired gut barrier function are key mediators in the gut-liver axis contributing to IFALD.
- Modified lipid emulsions show promise in reducing IFALD risk, reversing cholestasis, and mitigating complications, though hepatic fibrosis persistence requires further study.
Conclusions:
- Understanding the phases and mechanisms of IFALD is crucial for effective management.
- Therapeutic modifications of lipid emulsions represent a significant advancement in IFALD prevention and treatment.
- Ongoing research is needed to address the long-term implications of hepatic fibrosis and optimize patient care.
Abstract:
Development of intestinal failure-associated liver disease (IFALD) is a common complication of long-term parenteral nutrition (PN) in children and adults. The molecular and cellular mechanisms and the phases of IFALD are now being delineated. Components of PN lipid emulsions, including plant sterols, interact with hepatic innate immune activation promoted by products of gut bacterial overgrowth/dysbiosis and altered intestinal barrier function (gut-liver axis) and by episodes of sepsis to cause cholestasis and IFALD. New therapeutic strategies, including modifications of intravenous lipid emulsions to reduce pro-inflammatory fatty acids and plant sterol content, can lower the risk of IFALD, reverse cholestasis, and reduce complications, although the significance of persisting hepatic fibrosis is unknown. This review will provide an update on advances in the pathogenesis of IFALD, newer therapeutic and preventative strategies, and challenges that confront managing patients with IFALD.
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