Novel Lipid-Based Approaches to Pediatric Intestinal Failure–Associated Liver Disease

Diamond, Ivan; Pencharz, Paul B.; Feldman, Brian M.; Ling, Simon C.; Moore, Aideen M.; Wales, Paul W.

doi:10.1001/archpediatrics.2011.1896

Cited by 21 publications

(9 citation statements)

References 67 publications

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“…We have demonstrated that substituting FO for SO-based lipid emulsions or elimination of all intravenous lipids in PN solutions prevents cholestasis, hepatocyte injury, and activation of liver macrophages in mice with intestinal injury receiving PN for 7 days, replicating reports in human infants in whom infusion with FO-based PN or reduction of intravenous lipid dose improved PNALD (6–13). These results indicate that the absence of a lipid component in FO-based PN, rather than the presence of ω-3 fatty acids as proposed by others (7, 10, 11, 13), is likely the major mechanism of protection from liver injury and cholestasis.…”

Section: Discussionsupporting

confidence: 62%

“…The pathogenesis and etiology of PNALD remain poorly understood. Recent studies have focused on the possible contributing roles of lipid emulsions, which are obligate components of the PN solutions (6–13), and the absorption of bacterial products such as lipopolysaccharides (LPSs) from the compromised, inflamed intestinal mucosa (14, 15). …”

Section: Introductionmentioning

confidence: 99%

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Phytosterols Promote Liver Injury and Kupffer Cell Activation in Parenteral Nutrition–Associated Liver Disease

et al. 2013

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Parenteral nutrition–associated liver disease (PNALD) is a serious complication of PN in infants who do not tolerate enteral feedings, especially those with acquired or congenital intestinal diseases. Yet, the mechanisms underlying PNALD are poorly understood. It has been suggested that a component of soy oil (SO) lipid emulsions in PN solutions, such as plant sterols (phytosterols), may be responsible for PNALD, and that use of fish oil (FO)–based lipid emulsions may be protective. We used a mouse model of PNALD combining PN infusion with intestinal injury to demonstrate that SO-based PN solution causes liver damage and hepatic macrophage activation and that PN solutions that are FO-based or devoid of all lipids prevent these processes. We have furthermore demonstrated that a factor in the SO lipid emulsions, stigmasterol, promotes cholestasis, liver injury, and liver macrophage activation in this model and that this effect may be mediated through suppression of canalicular bile transporter expression (Abcb11/BSEP, Abcc2/MRP2) via antagonism of the nuclear receptors Fxr and Lxr, and failure of up-regulation of the hepatic sterol exporters (Abcg5/g8/ABCG5/8). This study provides experimental evidence that plant sterols in lipid emulsions are a major factor responsible for PNALD and that the absence or reduction of plant sterols is one of the mechanisms for hepatic protection in infants receiving FO-based PN or lipid minimization PN treatment. Modification of lipid constituents in PN solutions is thus a promising strategy to reduce incidence and severity of PNALD.

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Section: Discussionsupporting

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Phytosterols Promote Liver Injury and Kupffer Cell Activation in Parenteral Nutrition–Associated Liver Disease

et al. 2013

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“…4, 8, 24, 25 Most studies have been retrospective, used a historical comparison group, used different doses of lipid, and were conducted in patients with quite advanced IFALD. In addition, with the exception of improving biochemical measurements of cholesatsis and delaying the need for intestinal transplant evaluation (two important outcomes), there is evidence that the use of ILE containing ω-3 PUFA does not improve other important long-term clinical outcomes, such as the severity of hepatic fibrosis.…”

Section: Preventive and Therapeutic Approachesmentioning

confidence: 99%

Intestinal Microbiota, Lipids, and the Pathogenesis of Intestinal Failure–Associated Liver Disease

Lee

Sokol

2015

The Journal of Pediatrics

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“…ILE minimization can also lead to EFAD. To avoid the risks of EFAD, some advocate for using a mixture of Omegaven 1 gram/kg/day and Intralipid 1 gram/kg/day 37 . In children suspected to require long-term PN, our group limits soybean-based ILE to 1 gram/kg/day; if cholestasis occurs, we switch to fish oil-based ILE 1 gram/kg/day.…”

Section: Lipidsmentioning

confidence: 99%

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

Raphael

Duggan

2013

Semin Liver Dis

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Intestinal failure-associated liver disease (IFALD), a serious complication occurring in infants, children and adults exposed to long-term parenteral nutrition (PN), causes a wide-spectrum of disease, ranging from cholestasis and steatosis to fibrosis and eventually cirrhosis. Known host risk factors for IFALD include low birth weight, prematurity, short bowel syndrome and recurrent sepsis. The literature suggests that components of PN may also play a part of the multifactorial pathophysiology. Because some intravenous lipid emulsions (ILE) may contribute to inflammation and interfere with bile excretion, treatment with ILE minimization and/or ILEs composed primarily of omega-3 fatty acids can be helpful but requires careful monitoring for growth failure and essential fatty acid deficiency (EFAD). Data from randomized controlled trials are awaited to support widespread use of these approaches. Other IFALD treatments include cycling PN, ursodeoxycholic acid, sepsis prevention, photoprotection and polyvinylchloride-free tubing. Management and prevention of IFALD remains a clinical challenge.

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Novel Lipid-Based Approaches to Pediatric Intestinal Failure–Associated Liver Disease

Cited by 21 publications

References 67 publications

Phytosterols Promote Liver Injury and Kupffer Cell Activation in Parenteral Nutrition–Associated Liver Disease

Phytosterols Promote Liver Injury and Kupffer Cell Activation in Parenteral Nutrition–Associated Liver Disease

Intestinal Microbiota, Lipids, and the Pathogenesis of Intestinal Failure–Associated Liver Disease

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

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