Multicomponent parenteral lipid emulsions do not prevent liver injury in neonatal pigs with obstructive cholestasis

Authors: GUTHRIE, GREGORY - Baylor College Of Medicine; VONDEROHE, CAITLIN - Baylor College Of Medicine; HEBIB, VALERIA - Baylor College Of Medicine; STOLL, BARBARA - Baylor College Of Medicine; Burrin, Douglas

Submitted to: JCI Insight
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/10/2025
Publication Date: 4/17/2025
Citation: Guthrie, G., Vonderohe, C., Hebib, V.M., Stoll, B., Burrin, D.G. 2025. Multicomponent parenteral lipid emulsions do not prevent liver injury in neonatal pigs with obstructive cholestasis. JCI Insight. 10. https://doi.org/10.1172/jci.insight.189196.
DOI: https://doi.org/10.1172/jci.insight.189196

Interpretive Summary: Biliary atresia (BA) is a serious liver disease that affects babies. These babies often can't absorb fat and fat soluble nutrients from food because their liver can’t release bile, which helps absorb fats, into the intestine. To help them grow, they are often given a special liquid food through a catheter inserted into a vein (IV), called parenteral nutrition (PN). This special liquid food usually contains fats to provide energy. Traditionally, these fats come from soy-based oils (SLE). However, there's concern that these soy-based fats might actually harm the liver further, especially in babies with liver problems. Recently, a different kind of fat mixture called mixed lipid emulsions (MLE) has shown promise. The MLE contains fats from fish oil, olive oil, coconut oil, and soy oil and is more balanced in fat composition compared to SLE. In babies without BA, MLEs seem to prevent liver damage. The big question is whether they can help babies with BA, where the bile ducts (tubes that carry digestive fluid from the liver) are completely blocked. To find out, we used neonatal pigs that had their bile ducts surgically blocked to model the condition of BA. Some pigs were given MLEs through their IV, while others received the traditional soy-based fats (SLE) or were fed by mouth instead of IV. We found that the pigs given MLEs gained much more weight than the other groups. While we did see some changes in markers of liver injury, we didn't find clear evidence that MLEs prevented overall liver damage more than SLEs in this model. Even though we didn't see a big difference in liver damage, the significant weight gain in the pigs receiving MLEs suggests that MLE might be a better option for providing nutrition to babies with liver conditions like BA.

Technical Abstract: Biliary atresia (BA) is a pediatric liver disease that often necessitates parenteral nutrition (PN) to support growth due to impaired liver function. While soy-based lipid emulsions (SLE) are commonly used in PN, they may contribute to cholestatic liver injury. In contrast, mixed lipid emulsions (MLE) show promise in preventing cholestasis in infants without BA, potentially by restoring bile flow. However, their effectiveness in patients of complete bile duct obstruction, as seen in BA, remains uncertain. To explore the potential benefits of MLE in BA, we utilized a neonatal pig model of bile duct ligation (BDL). Pigs underwent either BDL or sham surgery and were subsequently fed either MLE or SLE via PN, or enterally with formula. The MLE-BDL pigs exhibited significantly greater weight gain compared with those fed SLE or formula enterally. Additionally, MLE-BDL pigs showed higher serum bile acid and '-glutamyl transferase concentrations compared with SLE-BDL pigs. However, no significant differences in liver injury, assessed by ductular reaction or fibrosis, were observed between MLE- and SLE-BDL pigs. Based on weight gain alone, MLE may be a superior lipid emulsion for use in neonates with obstructive cholestasis.