Intestinal failure-associated liver disease model: a reduced phytosterol intravenous lipid emulsion prevents liver injury

Scott C Fligor; Thomas I Hirsch; Savas T Tsikis; Amy Pan; Mikayla Quigley; Kathleen M Gura; Mark Puder

doi:10.1038/s41390-024-03753-9

Intestinal failure-associated liver disease model: a reduced phytosterol intravenous lipid emulsion prevents liver injury

Pediatr Res. 2024 Nov 27. doi: 10.1038/s41390-024-03753-9. Online ahead of print.

Authors

Scott C Fligor^{1

2}, Thomas I Hirsch^{1

2}, Savas T Tsikis^{1

2}, Amy Pan¹, Mikayla Quigley¹, Kathleen M Gura^{2

3}, Mark Puder^{4

5}

Affiliations

¹ Vascular Biology Program and the Department of Surgery, Boston Children's Hospital, Boston, MA, USA.
² Harvard Medical School, Boston, MA, USA.
³ Department of Pharmacy and the Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA, USA.
⁴ Vascular Biology Program and the Department of Surgery, Boston Children's Hospital, Boston, MA, USA. [email protected].
⁵ Harvard Medical School, Boston, MA, USA. [email protected].

PMID: 39592772
DOI: 10.1038/s41390-024-03753-9

Abstract

Background: Long-term parenteral nutrition in children often results in intestinal failure-associated liver disease (IFALD). Phytosterols are plant steroids in vegetable oil-based intravenous lipid emulsions (ILEs) that are associated with IFALD. We investigated whether a phytosterol-depleted soybean oil ILE, compared to standard soybean oil ILE, prevented hepatotoxicity in a murine IFALD model.

Methods: Eight-week-old male C57BL/6 J mice were provided a fat-free high carbohydrate liquid diet for 19 days. Mice were intravenously administered ILEs as the sole fat source: Intralipid® (commercially available soybean oil ILE), Omegaven® (commercially available fish oil ILE), a low phytosterol soybean oil ILE (L-SOLE) or a high phytosterol soybean oil ILE (H-SOLE) with matched alpha tocopherol content. On days 6, 12, and 18 mice were administered escalating intraperitoneal doses of lipopolysaccharide.

Results: Compared to chow controls, mice that received Intralipid® demonstrated elevated plasma biomarkers of liver injury and histologic liver disease (hepatosteatosis, histologic inflammation, F4/80 staining). L-SOLE prevented both biochemical and histologic liver injury. Administration of H-SOLE also prevented biochemical liver injury, but not steatosis.

Conclusion: The combination of phytosterol removal and alpha tocopherol supplementation may reduce the toxicity associated with parenteral use of soybean oil-based ILE. Low phytosterol soybean oil may be a valuable component in safer next generation ILEs.

Impact: Half of children receiving long-term parenteral nutrition develop intestinal failure-associated liver disease (IFALD). Standard intravenous lipid emulsions (ILEs) in parenteral nutrition are vegetable oil based and high in phytosterols (plant steroids); no low phytosterol vegetable oil-based ILE is available. Phytosterols in ILEs are associated with IFALD. In this study, a new phytosterol-depleted soybean oil was utilized in a laboratory-generated ILE. Use of the phytosterol-depleted soybean oil ILE prevented liver injury in a murine model of IFALD. Phytosterol-depleted soybean oil may be utilized as a component of less toxic next-generation ILEs.