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CC BY 4.0 · Semin Liver Dis
DOI: 10.1055/a-2545-7370
Review Article

Pathogenesis and Management of Intestinal Failure-Associated Liver Disease

Sasha-Jane Abi-Aad 
1   Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of South Florida Morsani College of Medicine, Tampa, Florida
,
Mark Lovell 
2   Department of Pathology, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado
,
Racha T. Khalaf 
1   Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of South Florida Morsani College of Medicine, Tampa, Florida
,
Ronald J. Sokol 
3   Department of Pediatrics, Digestive Health Institute, Children's Hospital Colorado, Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine, Aurora, Colorado
› Institutsangaben Funding R.J.S. receives funding from NCATS (UM1 TR004399) and NIDDK (U01 DK062453), both of the National Institutes of Health. R.T.K. receives funding from the Cystic Fibrosis Foundation (#005206Q123, #005583Q123).
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Abstract

Long-term parenteral nutrition (PN) has considerably improved the management of intestinal failure (IF) in children and adults, particularly those with short bowel syndrome; however, it carries a significant risk of hepatotoxicity, specifically, intestinal failure-associated liver disease (IFALD), also known as PN-associated liver disease. This review provides an update on the latest understanding of IFALD pathogenesis, emerging therapies, and ongoing challenges in the management of this complication. A number of factors are associated with the development of IFALD. PN lipid emulsions, phytosterol exposure, bacterial dysbiosis, an altered gut–liver axis, and episodes of sepsis disrupt bile acid homeostasis and promote liver inflammation in the active phase of IFALD, favoring the development of PN-associated cholestasis (PNAC) and the more chronic form of steatohepatitis with fibrosis. Based on the identification of pathophysiological pathways, potential therapies are being studied in preclinical and clinical trials, including lipid emulsion modifications; targeted therapies such as Farnesoid X receptor (FXR) and liver receptor homolog 1 (LRH-1) agonists, tumor necrosis factor inhibitors, glucagon-like peptide-2 analogs; microbiome modulation; and supplementation with choline and antioxidants. In conclusion, the pathogenesis of IFALD is complex, and PN dependence and liver injury remain challenging, particularly in patients with IF who cannot advance to enteral nutrition and be weaned off PN.

Keywords

intestinal failure-associated liver disease - cholestasis - intestinal failure - lipid emulsions - parenteral nutrition-associated liver disease


Publikationsverlauf

Eingereicht: 14. Dezember 2024

Angenommen: 14. Februar 2025

Accepted Manuscript online:
27. Februar 2025

Artikel online veröffentlicht:
18. März 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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