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Intestinal failure-associated liver disease (IFALD): insights into pathogenesis and advances in management
Way S Lee1,2, Kee S Chew1, Ruey T Ng1
1Department of Paediatrics, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia.
Insights
Premature infants and children with intestinal failure (IF) are at risk for liver disease (IFALD). Soybean-oil-based lipid emulsions may contribute, necessitating further research into effective prevention and treatment strategies.
Area of Science:
- Pediatric Gastroenterology
- Hepatology
- Neonatology
Background:
- Intestinal failure-associated liver disease (IFALD) affects premature infants and children with short bowel syndrome dependent on parenteral nutrition (PN).
- IFALD is characterized by cholestasis and fibrosis in children, and steatohepatitis in adults.
- Potential contributing factors include the gut microbiome, intestinal permeability, hepatic innate immunity, and soybean-oil-based intravenous lipid emulsions (SO-ILE).
Purpose of the Study:
- To review the pathogenesis and management of IFALD.
- To highlight the role of SO-ILEs, specifically stigmasterol, in IFALD development.
- To emphasize the need for high-quality clinical trials to evaluate IFALD prevention and treatment strategies.
Main Methods:
- Review of existing literature on IFALD pathogenesis and management.
- Identification of key factors implicated in IFALD, including SO-ILEs and stigmasterol.
- Assessment of current prevention and treatment strategies and their evidence base.
Main Results:
- Soybean-oil-based intravenous lipid emulsions (SO-ILEs) are a significant focus in IFALD pathogenesis, with stigmasterol identified as a key component.
- Some evidence suggests reducing or replacing SO-ILEs can reverse IFALD, but long-term safety and efficacy require study.
- Medical and surgical interventions to improve intestinal adaptation and prevent infections are important preventative measures.
Conclusions:
- High-quality, prospective clinical trials with defined endpoints are crucial for validating IFALD prevention and treatment strategies.
- Further research is needed to understand the long-term effectiveness and safety of altering lipid emulsion composition.
- A multi-faceted approach, including optimizing PN, enhancing enteral feeding, and preventing complications, is essential for managing IFALD.
Abstract:
Premature infants and children with intestinal failure (IF) or short bowel syndrome are susceptible to intestinal failure-associated liver disease (IFALD, previously referred to as parenteral nutrition-associated liver disease, or PNALD). IFALD in children is characterized by progressive cholestasis and biliary fibrosis, and steatohepatitis in adults, and is seen in individuals dependent upon prolonged administration of PN. Many factors have been proposed as contributing to the pathogenesis of IFALD. In recent years, the focus has been on the potential synergistic roles of the intestinal microbiome, increased intestinal permeability, activation of hepatic innate immune pathways, and the use of intravenous soybean-oil-based intravenous lipid emulsions (SO-ILE). In vitro and in vivo studies have identified stigmasterol, a component of the plant sterols present in SO-ILE, as playing an important role. Although various strategies have been adopted to prevent or reverse IFALD, most suffer from a lack of strong evidence supported by well-designed, prospective clinical trials with clearly defined endpoints. Reduction in the amount of SO-ILEs or replacement with non-SO-ILEs has been shown to reverse IFALD although safety and long-term effectiveness have not been studied. Medical and surgical modalities to increase intestinal adaptation, advance enteral feedings, and prevent central line bloodstream infections are also important preventative strategies. There is a continued need to conduct high-quality, prospective trials with clearly define outcome measures to ascertain the potential benefits of these strategies.
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