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      ESPGHAN Committee on Nutrition Position Paper. Intravenous Lipid Emulsions and Risk of Hepatotoxicity in Infants and Children : a Systematic Review and Meta-analysis

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          Abstract

          The aim of the present article was to perform a systematic review with meta-analysis of available scientific evidence regarding the role of different intravenous lipid emulsions (ILE) in the pathogenesis of cholestasis and parenteral nutrition-associated liver disease. A systematic review of the literature (up to March 2015) identified 23 randomized controlled trials (RCTs). Of these, 17 were performed in preterm infants or critically ill neonates with a short duration of intervention, 2 in older children with short-term use (following surgery or bone marrow transplantation), 1 in neonates with long-term use, and 3 in infants and children receiving long-term parenteral nutrition (PN). Meta-analysis showed no differences in the rate of cholestasis or bilirubin levels associated with short-term use of different ILEs. Because of high heterogeneity of the long-term studies no meta-analysis could be performed. Available studies found that the use of multicomponent fish oil (FO)-containing ILE compared with pure soya bean oil (SO), ILE-reduced liver enzymes, and bilirubin levels in noncholestatic children on long-term PN and one other RCT found that FO-based ILE-reversed cholestasis in a proportion of patients. The ESPGHAN Committee on Nutrition concludes that there is no evidence of a difference in rates of cholestasis or bilirubin levels between different ILE for short-term use in neonates. The use of multicomponent FO-containing ILE may contribute to a decrease in total bilirubin levels in children with IF on prolonged PN. Well-designed RCTs are, however, lacking and long-term effects have not been determined.

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          Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis.

          Mice lacking the nuclear bile acid receptor FXR/BAR developed normally and were outwardly identical to wild-type littermates. FXR/BAR null mice were distinguished from wild-type mice by elevated serum bile acid, cholesterol, and triglycerides, increased hepatic cholesterol and triglycerides, and a proatherogenic serum lipoprotein profile. FXR/BAR null mice also had reduced bile acid pools and reduced fecal bile acid excretion due to decreased expression of the major hepatic canalicular bile acid transport protein. Bile acid repression and induction of cholesterol 7alpha-hydroxylase and the ileal bile acid binding protein, respectively, did not occur in FXR/BAR null mice, establishing the regulatory role of FXR/BAR for the expression of these genes in vivo. These data demonstrate that FXR/BAR is critical for bile acid and lipid homeostasis by virtue of its role as an intracellular bile acid sensor.
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            Molecular pathogenesis of cholestasis.

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              Prevalence of liver disease and contributing factors in patients receiving home parenteral nutrition for permanent intestinal failure.

              Liver cholestasis can be a life-threatening complication during home parenteral nutrition and may lead to combined liver-intestinal transplantation. To assess the prevalence of home parenteral nutrition-related liver disease and its contributing factors in patients with permanent intestinal failure. Prospective cohort study. Two approved home parenteral nutrition centers. 90 patients with permanent intestinal failure who were receiving home parenteral nutrition were enrolled from 1985 to 1996. Clinical, biological, endoscopic, and ultrasonographic follow-up. Histologic examination of the liver was done in 57 patients (112 liver biopsies). The Kaplan-Meier method was used to determine the actuarial occurrence of chronic cholestasis and complicated home parenteral nutrition-related liver disease (bilirubin level > or =60 micromol/L [3.5 mg/dL], factor V level < or =50%, portal hypertension, encephalopathy, ascites, gastrointestinal bleeding, or histologically proven extensive fibrosis or cirrhosis). Contributing factors were assessed by using univariate and multivariate (Cox model) analysis. 58 patients (65%) developed chronic cholestasis after a median of 6 months (range, 3 to 132 months), and 37 (41.5%) developed complicated home parenteral nutrition-related liver disease after a median of 17 months (range, 2 to 155 months). Of these patients, 17 showed extensive fibrosis after 26 months (range, 2 to 148 months) and 5 had cirrhosis after 37 months (range, 26 to 77 months). The prevalence of complicated home parenteral nutrition-related liver disease was 26%+/-9% at 2 years and 50%+/-13% at 6 years. Six patients died of liver disease (22% of all deaths). In multivariate analysis, chronic cholestasis was significantly associated with a parenteral nutrition-independent risk for liver disease, a bowel remnant shorter than 50 cm in length, and a parenteral lipid intake of 1 g/kg of body weight per day or more (omega-6-rich long-chain triglycerides), whereas complicated home parenteral nutrition-related liver disease was significantly associated with chronic cholestasis and lipid parenteral intake of 1 g/kg per day or more. The prevalence of complicated home parenteral nutrition-related liver disease increased with longer duration of parenteral nutrition. This condition was one of the main causes of death in patients with permanent intestinal failure. Parenteral intake of omega-6-rich long-chain triglycerides lipid emulsion consisting of less than 1 g/kg per day is recommended in these patients.
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                Author and article information

                Journal
                Journal of Pediatric Gastroenterology and Nutrition
                Journal of Pediatric Gastroenterology and Nutrition
                Ovid Technologies (Wolters Kluwer Health)
                0277-2116
                2016
                May 2016
                : 62
                : 5
                : 776-792
                Article
                10.1097/MPG.0000000000001121
                26825766
                8da954fb-e4bf-44c5-ab3e-6a8282ed7415
                © 2016
                History

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