Persistence of hepatic fibrosis in pediatric intestinal failure patients treated with intravenous fish oil lipid emulsion

Belza, Christina; Thompson, R P; Somers, Gino R.; Silva, Nicole de; Fitzgerald, Kevin T.; Steinberg, Karen K.; Courtney‐Martin, Glenda; Wales, Paul W.; Avitzur, Yaron

doi:10.1016/j.jpedsurg.2017.01.048

Cited by 23 publications

(7 citation statements)

References 49 publications

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“…Even though the guidelines of the American society of parenteral and enteral nutrition suggest that more evidences are required in order to recommend it [ 22 ], SMOFlipids have been adopted by an increasing number of intestinal rehabilitation units in the United States. Fibrosis may, however, develop or worsen, despite a normal bilirubin level, as was seen in a small series of children on long-term PN, with some of them ultimately needing transplantation [ 76 , 77 ]. Furthermore, liver fibrosis can persist despite the normalization of biochemistry and PN weaning [ 78 ].…”

Section: Prevention Of Ifaldmentioning

confidence: 99%

Prevention and Treatment of Intestinal Failure-Associated Liver Disease in Children

et al. 2018

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Intestinal failure-associated liver disease (IFALD) is a threatening complication for children on long-term parenteral nutrition because of intestinal failure. When progressive and intractable, it may jeopardize intestinal rehabilitation and lead to combined liver and intestinal transplantation. The institution of dedicated intestinal failure centers has dramatically decreased the incidence of such complication. IFALD may rapidly fade away if very early management aimed at preventing progression to end-stage liver disease is provided. In this review, we address the etiology and risk factors of IFALD in order to introduce pillars of prevention (nutritional management and catheter-related infections control). The latest evidence of therapeutic strategies, such as medical and surgical treatments, is also discussed.

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Section: Prevention Of Ifaldmentioning

confidence: 99%

Prevention and Treatment of Intestinal Failure-Associated Liver Disease in Children

et al. 2018

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“…The pathogenesis of PNAC involves, at least in part, hepatic macrophage activation by intestinally absorbed LPS as well as infused phytosterols present in IV lipid emulsions. PNAC in human infants responds clinically in only a subset of patients to a switch from soy-based lipid emulsions to lipid emulsions that contain reduced phytosterols (eg, fish oil-based emulsions), and hepatic fibrosis persists and may even progress in those responding to lipid modifications, 30 leaving an unmet need for new therapeutic and preventive strategies. We reported the protective role of LRH-1 in PNAC pathogenesis in a murine model 4 .…”

Section: Discussionmentioning

confidence: 99%

LRH-1 agonist DLPC through STAT6 promotes macrophage polarization and prevents parenteral nutrition-associated cholestasis in mice

Ghosh,

Devereaux,

Liu

et al. 2023

Hepatology

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Background & Aims: Parenteral nutrition associated cholestasis (PNAC) is important complication in patients with intestinal failure with reduced LRH-1 expression. Here, we hypothesized that LRH-1 activation by its agonist, dilauroylphosphatidylcholine (DLPC), would trigger STAT6 signaling and hepatic macrophage polarization that would mediate hepatic protection in PNAC. Approach & Results: PNAC mouse model (oral DSSx4d followed by PNx14d; DSS-PN) was treated with LRH-1 agonist DLPC (30 mg/kg/day) intravenously. DLPC treatment prevented liver injury and cholestasis while inducing hepatic mRNA expression of Nr5a2), Abcb11, Abcg5, Abcg8, Nr0b2 and Abcc2 mRNA, all of which were reduced in PNAC mice. To determine the mechanism of DLPC effect, we performed RNA-sequencing analysis of liver from Chow, DSS-PN and DSS-PN/DLPC mice, which revealed DLPC upregulation of the anti-inflammatory STAT6 pathway. In intrahepatic mononuclear cells from PNAC mice, DLPC treatment prevented upregulation of pro-inflammatory (M1) genes, suppressed activation of NFκB and induced phosphorylation of STAT6 and its target genes, indicating M2 macrophage polarization. In vitro incubation of DLPC with cultured macrophages showed that the increased Il-1b and Tnf induced by exposure to LPS or phytosterols was reduced significantly, which was associated with increased STAT6 binding to promoters of its target genes. Suppression of STAT6 expression by siRNA in THP-1 cells exposed to LPS, phytosterols or both resulted in enhanced elevation of IL-1B mRNA expression. Furthermore, protective effect of DLPC in THP-1 cells was abrogated by STAT6 siRNA. Conclusions: These results indicate that activation of LRH-1 by DLPC may protect from PNAC liver injury through STAT6-mediated macrophage polarization.

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“…Although enteral feedings were encouraged and are considered an important tool for the prevention or reversal of IFALD, we were unable to collect dietary intake information due to the limitations of our data collection. Another study limitation was the lack of criterion standard hepatocellular injury measurement, such as liver biopsy, because it is not an institutional standard of practice to perform routine liver biopsies (27). We collect liver ultrasound with Doppler and transient elastography measurements every 1 to 2 years (28), and we plan on reporting such findings in CLE‐treated subjects in the future.…”

Section: Discussionmentioning

confidence: 99%

One‐year Experience With Composite Intravenous Lipid Emulsion in Children on Home Parenteral Nutrition

Raphael¹,

Mitchell²,

Carey³

et al. 2020

J. pediatr. gastroenterol. nutr.

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Background: Composite lipid emulsion (CLE) composed of soybean oil, medium-chain triglycerides, olive oil, and fish oil is approved in the US for parenterally fed adults. For stable children discharged on home parenteral nutrition (HPN) without cholestasis (direct bilirubin > 2.0 mg/dL), CLE has theoretical benefits over soybean-based intravenous lipid emulsion due to reduced phytosterol exposure with higher calorie support to permit reduced glucose infusion rates (GIRs), omega-3 supplementation, and supplemental α-tocopherol. Methods: In this prospective, single-center open-label research study, safety and efficacy outcomes were evaluated in patients on HPN younger than 18 years treated with CLE at 1 to 3 g · kg−1 · day−1 over 12 months. The primary outcome was change in anthropometrics and GIRs compared with baseline. Secondary outcomes were changes in fatty acid profiles and liver function and enzyme tests compared with baseline. Results: Fifty-seven subjects were treated with a median age of 7 years. The diagnosis was short bowel syndrome in 72%. Change in practice was associated with a decrease in mean GIRs from 17 to 14 mg · kg−1 · h−1 at 4 to 6 months postbaseline and beyond with a coincidental decline in mean arachidonic acid and stable growth parameters. No significant adverse events were noted. Conclusions: CLE was safe and well-tolerated in stable children on HPN at 1 year, but further studies are needed in this population to appreciate long-term outcomes.

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Persistence of hepatic fibrosis in pediatric intestinal failure patients treated with intravenous fish oil lipid emulsion

Cited by 23 publications

References 49 publications

Prevention and Treatment of Intestinal Failure-Associated Liver Disease in Children

Prevention and Treatment of Intestinal Failure-Associated Liver Disease in Children

LRH-1 agonist DLPC through STAT6 promotes macrophage polarization and prevents parenteral nutrition-associated cholestasis in mice

One‐year Experience With Composite Intravenous Lipid Emulsion in Children on Home Parenteral Nutrition

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