Pediatric intestinal failure-associated liver disease
Cathleen M Courtney1, Brad W Warner
1aDivision of Pediatric Surgery, St. Louis Children's Hospital bDepartment of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
Insights
Intestinal failure-associated liver disease (IFALD) is a major cause of mortality in pediatric patients. Novel lipid emulsions show promise in preventing and treating IFALD by reducing inflammation and improving bile flow.
Area of Science:
- Pediatric Gastroenterology
- Hepatology
- Parenteral Nutrition
Background:
- Intestinal failure-associated liver disease (IFALD) is a significant complication in pediatric patients requiring parenteral nutrition.
- The multifactorial nature of IFALD pathogenesis involves gut microbiome alterations, sepsis, and lack of enteral intake.
Purpose of the Study:
- To provide updated information on the definition, pathophysiology, treatment, and prevention of IFALD in pediatric patients.
- To highlight recent advancements in understanding IFALD molecular pathways and therapeutic strategies.
Main Methods:
- Literature review focusing on current research regarding IFALD.
- Analysis of molecular pathways, including Toll-like receptor 4 and farnesoid X receptor.
- Evaluation of lipid composition in parenteral nutrition and its impact on IFALD.
Main Results:
- IFALD pathogenesis is complex, involving proinflammatory cytokines and altered bile acid synthesis.
- Lipid emulsions with a reduced omega-6-to-omega-3 polyunsaturated fatty acid ratio may improve bile flow and decrease hepatic inflammation.
- Long-term effects of alternative lipid emulsions require further investigation.
Conclusions:
- IFALD remains a leading cause of mortality in pediatric intestinal failure.
- Novel lipid formulations offer promising alternatives to traditional soy-based formulas for reducing cholestasis.
- Addressing risk factors like gut dysbiosis and sepsis is crucial for IFALD management.
Purpose Of Review:
The goal of this review is to provide updates on the definition, pathophysiology, treatment, and prevention of intestinal failure-associated liver disease (IFALD) that are relevant to care of pediatric patients.
Recent Findings:
Current literature emphasizes the multifactorial nature of IFALD. The pathogenesis is still largely unknown; however, molecular pathways have been identified. Key to these pathways are proinflammatory cytokines involved in hepatic inflammation and bile acids synthesis such as Toll-like receptor 4 and farnesoid X receptor, respectively. Research for prevention and treatment is aimed at alleviating risk factors associated with IFALD, principally those associated with parental nutrition. Multiple nutrients and amino acids are relevant to the development of IFALD, but lipid composition has been the primary focus. Lipid emulsions with a lower ratio of omega-6-to-omega-3 polyunsaturated fatty acids (FAs) appear to improve bile flow and decrease intrahepatic inflammation. Long-term consequences of these alternative lipid emulsions are yet to be determined.
Summary:
IFALD remains the greatest contributor of mortality in patients with intestinal failure. Many factors contribute to its development, namely, alterations in the gut microbiome, sepsis, and lack of enteral intake. Novel combinations of lipid formulations are promising alternatives to purely soy-based formulas to reduce cholestasis.
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