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Intestinal failure-associated liver disease in infants

Kathleen M Gura, PharmD, BCNSP, FASHP
Scott A Elisofon, MD
Section Editors
Steven A Abrams, MD
Elizabeth B Rand, MD
Deputy Editor
Alison G Hoppin, MD


A substantial proportion of infants who depend upon parenteral nutrition (PN) because of intestinal failure develop cholestatic liver disease [1]. The disorder is particularly common among infants with a history of prematurity and/or bowel resection (short bowel syndrome), and is a major cause of morbidity, liver transplantation, and death in these patients.

Intestinal failure-associated liver disease (IFALD) is less common and generally less severe among older children and adults, but may occur in those undergoing long-term treatment with PN. The pathogenesis, clinical features and management of IFALD are discussed in this topic review. Related discussions about the management of parenteral and enteral nutrition are discussed in separate topic reviews:

(See "Parenteral nutrition in infants and children".)

(See "Parenteral nutrition in premature infants".)

(See "Overview of enteral nutrition in infants and children".)

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Literature review current through: Nov 2017. | This topic last updated: Sep 29, 2017.
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  1. Kelly DA. Liver complications of pediatric parenteral nutrition--epidemiology. Nutrition 1998; 14:153.
  2. Lacaille F, Gupte G, Colomb V, et al. Intestinal failure-associated liver disease: a position paper of the ESPGHAN Working Group of Intestinal Failure and Intestinal Transplantation. J Pediatr Gastroenterol Nutr 2015; 60:272.
  3. Cavicchi M, Beau P, Crenn P, et al. Prevalence of liver disease and contributing factors in patients receiving home parenteral nutrition for permanent intestinal failure. Ann Intern Med 2000; 132:525.
  4. Kelly DA. Intestinal failure-associated liver disease: what do we know today? Gastroenterology 2006; 130:S70.
  5. Cooper A, Floyd TF, Ross AJ 3rd, et al. Morbidity and mortality of short-bowel syndrome acquired in infancy: an update. J Pediatr Surg 1984; 19:711.
  6. Christensen RD, Henry E, Wiedmeier SE, et al. Identifying patients, on the first day of life, at high-risk of developing parenteral nutrition-associated liver disease. J Perinatol 2007; 27:284.
  7. Moss RL, Amii LA. New approaches to understanding the etiology and treatment of total parenteral nutrition-associated cholestasis. Semin Pediatr Surg 1999; 8:140.
  8. Pereira GR, Sherman MS, DiGiacomo J, et al. Hyperalimentation-induced cholestasis. Increased incidence and severity in premature infants. Am J Dis Child 1981; 135:842.
  9. Robinson DT, Ehrenkranz RA. Parenteral nutrition-associated cholestasis in small for gestational age infants. J Pediatr 2008; 152:59.
  10. Beale EF, Nelson RM, Bucciarelli RL, et al. Intrahepatic cholestasis associated with parenteral nutrition in premature infants. Pediatrics 1979; 64:342.
  11. Beath SV, Davies P, Papadopoulou A, et al. Parenteral nutrition-related cholestasis in postsurgical neonates: multivariate analysis of risk factors. J Pediatr Surg 1996; 31:604.
  12. Teitelbaum DH. Parenteral nutrition-associated cholestasis. Curr Opin Pediatr 1997; 9:270.
  13. Sondheimer JM, Asturias E, Cadnapaphornchai M. Infection and cholestasis in neonates with intestinal resection and long-term parenteral nutrition. J Pediatr Gastroenterol Nutr 1998; 27:131.
  14. Wolf A, Pohlandt F. Bacterial infection: the main cause of acute cholestasis in newborn infants receiving short-term parenteral nutrition. J Pediatr Gastroenterol Nutr 1989; 8:297.
  15. Cole CR, Frem JC, Schmotzer B, et al. The rate of bloodstream infection is high in infants with short bowel syndrome: relationship with small bowel bacterial overgrowth, enteral feeding, and inflammatory and immune responses. J Pediatr 2010; 156:941.
  16. Diamanti A, Basso MS, Castro M, et al. Irreversible intestinal failure: prevalence and prognostic factors. J Pediatr Gastroenterol Nutr 2008; 47:450.
  17. Aprahamian CJ, Chen M, Yang Y, et al. Two-hit rat model of short bowel syndrome and sepsis: independent of total parenteral nutrition, short bowel syndrome is proinflammatory and injurious to the liver. J Pediatr Surg 2007; 42:992.
  18. Slicker J, Vermilyea S. Pediatric parenteral nutrition: putting the microscope on macronutrients and micronutrients. Nutr Clin Pract 2009; 24:481.
  19. Duro D, Mitchell PD, Kalish LA, et al. Risk factors for parenteral nutrition–associated liver disease following surgical therapy for necrotizing enterocolitis: A Glaser Pediatric Research Network Study [corrected]. J Pediatr Gastroenterol Nutr 2011; 52:595.
  20. Spencer AU, Neaga A, West B, et al. Pediatric short bowel syndrome: redefining predictors of success. Ann Surg 2005; 242:403.
  21. Pakarinen MP, Koivusalo AI, Rintala RJ. Outcomes of intestinal failure--a comparison between children with short bowel and dysmotile intestine. J Pediatr Surg 2009; 44:2139.
  22. Alwayn IP, Gura K, Nosé V, et al. Omega-3 fatty acid supplementation prevents hepatic steatosis in a murine model of nonalcoholic fatty liver disease. Pediatr Res 2005; 57:445.
  23. Van Aerde JE, Duerksen DR, Gramlich L, et al. Intravenous fish oil emulsion attenuates total parenteral nutrition-induced cholestasis in newborn piglets. Pediatr Res 1999; 45:202.
  24. Gawecka A, Michalkiewicz J, Kornacka MK, et al. Immunologic properties differ in preterm infants fed olive oil vs soy-based lipid emulsions during parenteral nutrition. JPEN J Parenter Enteral Nutr 2008; 32:448.
  25. Raptis DA, Limani P, Jang JH, et al. GPR120 on Kupffer cells mediates hepatoprotective effects of ω3-fatty acids. J Hepatol 2014; 60:625.
  26. Clayton PT, Whitfield P, Iyer K. The role of phytosterols in the pathogenesis of liver complications of pediatric parenteral nutrition. Nutrition 1998; 14:158.
  27. Carter BA, Taylor OA, Prendergast DR, et al. Stigmasterol, a soy lipid-derived phytosterol, is an antagonist of the bile acid nuclear receptor FXR. Pediatr Res 2007; 62:301.
  28. Xu Z, Harvey KA, Pavlina T, et al. Steroidal compounds in commercial parenteral lipid emulsions. Nutrients 2012; 4:904.
  29. Shattuck KE, Grinnell CD, Rassin DK. Amino acid infusions induce reversible, dose-related decreases in bile flow in the isolated rat liver. JPEN J Parenter Enteral Nutr 1993; 17:171.
  30. Moss RL, Haynes AL, Pastuszyn A, Glew RH. Methionine infusion reproduces liver injury of parenteral nutrition cholestasis. Pediatr Res 1999; 45:664.
  31. Black DD, Suttle EA, Whitington PF, et al. The effect of short-term total parenteral nutrition on hepatic function in the human neonate: a prospective randomized study demonstrating alteration of hepatic canalicular function. J Pediatr 1981; 99:445.
  32. Bhatia J, Moslen MT, Haque AK, et al. Total parenteral nutrition-associated alterations in hepatobiliary function and histology in rats: is light exposure a clue? Pediatr Res 1993; 33:487.
  33. Wright K, Ernst KD, Gaylord MS, et al. Increased incidence of parenteral nutrition-associated cholestasis with aminosyn PF compared to trophamine. J Perinatol 2003; 23:444.
  34. Forchielli ML, Gura KM, Sandler R, Lo C. Aminosyn PF or trophamine: which provides more protection from cholestasis associated with total parenteral nutrition? J Pediatr Gastroenterol Nutr 1995; 21:374.
  35. Steinbach M, Clark RH, Kelleher AS, et al. Demographic and nutritional factors associated with prolonged cholestatic jaundice in the premature infant. J Perinatol 2008; 28:129.
  36. Clark RH, Chace DH, Spitzer AR, Pediatrix Amino Acid Study Group. Effects of two different doses of amino acid supplementation on growth and blood amino acid levels in premature neonates admitted to the neonatal intensive care unit: a randomized, controlled trial. Pediatrics 2007; 120:1286.
  37. Blau J, Sridhar S, Mathieson S, Chawla A. Effects of protein/nonprotein caloric intake on parenteral nutrition associated cholestasis in premature infants weighing 600-1000 grams. JPEN J Parenter Enteral Nutr 2007; 31:487.
  38. Zaman N, Tam YK, Jewell LD, Coutts RT. Effects of taurine supplementation in parenteral nutrition-associated hepatosteatosis and lidocaine metabolism. A study using isolated rat liver perfusion. Drug Metab Dispos 1996; 24:534.
  39. Guertin F, Roy CC, Lepage G, et al. Effect of taurine on total parenteral nutrition-associated cholestasis. JPEN J Parenter Enteral Nutr 1991; 15:247.
  40. Dahlström KA, Ament ME, Laidlaw SA, Kopple JD. Plasma amino acid concentrations in children receiving long-term parenteral nutrition. J Pediatr Gastroenterol Nutr 1988; 7:748.
  41. Mehta K, Van Thiel DH, Shah N, Mobarhan S. Nonalcoholic fatty liver disease: pathogenesis and the role of antioxidants. Nutr Rev 2002; 60:289.
  42. Li S, Nussbaum MS, Teague D, et al. Increasing dextrose concentrations in total parenteral nutrition (TPN) causes alterations in hepatic morphology and plasma levels of insulin and glucagon in rats. J Surg Res 1988; 44:639.
  43. von Rettberg H, Hannman T, Subotic U, et al. Use of di(2-ethylhexyl)phthalate-containing infusion systems increases the risk for cholestasis. Pediatrics 2009; 124:710.
  44. McMillan NB, Mulroy C, MacKay MW, et al. Correlation of cholestasis with serum copper and whole-blood manganese levels in pediatric patients. Nutr Clin Pract 2008; 23:161.
  45. Fell JM, Reynolds AP, Meadows N, et al. Manganese toxicity in children receiving long-term parenteral nutrition. Lancet 1996; 347:1218.
  46. Blaszyk H, Wild PJ, Oliveira A, et al. Hepatic copper in patients receiving long-term total parenteral nutrition. J Clin Gastroenterol 2005; 39:318.
  47. Rangel SJ, Calkins CM, Cowles RA, et al. Parenteral nutrition-associated cholestasis: an American Pediatric Surgical Association Outcomes and Clinical Trials Committee systematic review. J Pediatr Surg 2012; 47:225.
  48. Greene HL, Hambidge KM, Schanler R, Tsang RC. Guidelines for the use of vitamins, trace elements, calcium, magnesium, and phosphorus in infants and children receiving total parenteral nutrition: report of the Subcommittee on Pediatric Parenteral Nutrient Requirements from the Committee on Clinical Practice Issues of the American Society for Clinical Nutrition. Am J Clin Nutr 1988; 48:1324.
  49. Hurwitz M, Garcia MG, Poole RL, Kerner JA. Copper deficiency during parenteral nutrition: a report of four pediatric cases. Nutr Clin Pract 2004; 19:305.
  50. Klein GL, Goldblum RM, Moslen MT, et al. Increased biliary transferrin excretion following parenteral aluminium administration to rats. Pharmacol Toxicol 1993; 72:373.
  51. Parenteral drug products containing aluminum as an ingredient or a contaminant: response to Food and Drug Administration notice of intent and request for information. ASCN/A.S.P.E.N. Working Group on Standards for Aluminum Content of Parenteral Nutrition Solutions. JPEN J Parenter Enteral Nutr 1991; 15:194.
  52. Food and Drug Administration. Aluminium in large and small volume parenterals used in total parenteral nutrition. Fed Regist 2000; 65:4103.
  53. Poole RL, Hintz SR, Mackenzie NI, Kerner JA Jr. Aluminum exposure from pediatric parenteral nutrition: meeting the new FDA regulation. JPEN J Parenter Enteral Nutr 2008; 32:242.
  54. Smith BS, Kothari H, Hayes BD, et al. Effect of additive selection on calculated aluminum content of parenteral nutrient solutions. Am J Health Syst Pharm 2007; 64:730.
  55. Hofmann AF. Defective biliary secretion during total parenteral nutrition: probable mechanisms and possible solutions. J Pediatr Gastroenterol Nutr 1995; 20:376.
  56. Nightingale JM. Hepatobiliary, renal and bone complications of intestinal failure. Best Pract Res Clin Gastroenterol 2003; 17:907.
  57. Zambrano E, El-Hennawy M, Ehrenkranz RA, et al. Total parenteral nutrition induced liver pathology: an autopsy series of 24 newborn cases. Pediatr Dev Pathol 2004; 7:425.
  58. Yang CF, Lee M, Valim C, et al. Persistent alanine aminotransferase elevations in children with parenteral nutrition-associated liver disease. J Pediatr Surg 2009; 44:1084.
  59. Forchielli ML, Walker WA. Nutritional factors contributing to the development of cholestasis during total parenteral nutrition. Adv Pediatr 2003; 50:245.
  60. Javid PJ, Collier S, Richardson D, et al. The role of enteral nutrition in the reversal of parenteral nutrition-associated liver dysfunction in infants. J Pediatr Surg 2005; 40:1015.
  61. Vanderhoof JA, Langnas AN. Short-bowel syndrome in children and adults. Gastroenterology 1997; 113:1767.
  62. Nasr A, Avitzur Y, Ng VL, et al. The use of conjugated hyperbilirubinemia greater than 100 micromol/L as an indicator of irreversible liver disease in infants with short bowel syndrome. J Pediatr Surg 2007; 42:359.
  63. Kaufman SS, Pehlivanova M, Fennelly EM, et al. Predicting liver failure in parenteral nutrition-dependent short bowel syndrome of infancy. J Pediatr 2010; 156:580.
  64. Willis TC, Carter BA, Rogers SP, et al. High rates of mortality and morbidity occur in infants with parenteral nutrition-associated cholestasis. JPEN J Parenter Enteral Nutr 2010; 34:32.
  65. Moss RL, Das JB, Raffensperger JG. Total parenteral nutrition-associated cholestasis: clinical and histopathologic correlation. J Pediatr Surg 1993; 28:1270.
  66. Mullick FG, Moran CA, Ishak KG. Total parenteral nutrition: a histopathologic analysis of the liver changes in 20 children. Mod Pathol 1994; 7:190.
  67. Fitzgibbons SC, Jones BA, Hull MA, et al. Relationship between biopsy-proven parenteralnutrition-associated liver fibrosis and biochemical cholestasis in children with short bowel syndrome. J Pediatr Surg 2010; 45:95.
  68. Jeejeebhoy KN. Management of short bowel syndrome: avoidance of total parenteral nutrition. Gastroenterology 2006; 130:S60.
  69. Goulet O. Short bowel syndrome in pediatric patients. Nutrition 1998; 14:784.
  70. Perdikis DA, Basson MD. Basal nutrition promotes human intestinal epithelial (Caco-2) proliferation, brush border enzyme activity, and motility. Crit Care Med 1997; 25:159.
  71. Pimenta HP, Moreira ME, Rocha AD, et al. Effects of non-nutritive sucking and oral stimulation on breastfeeding rates for preterm, low birth weight infants: a randomized clinical trial. J Pediatr (Rio J) 2008; 84:423.
  72. Torres C, Sudan D, Vanderhoof J, et al. Role of an intestinal rehabilitation program in the treatment of advanced intestinal failure. J Pediatr Gastroenterol Nutr 2007; 45:204.
  73. Wales PW, Allen N, Worthington P, et al. A.S.P.E.N. clinical guidelines: support of pediatric patients with intestinal failure at risk of parenteral nutrition-associated liver disease. JPEN J Parenter Enteral Nutr 2014; 38:538.
  74. Komura J, Yano H, Tanaka Y, Tsuru T. Increased incidence of cholestasis during total parenteral nutrition in children--factors affecting stone formation. Kurume Med J 1993; 40:7.
  75. Messing B, Colombel JF, Heresbach D, et al. Chronic cholestasis and macronutrient excess in patients treated with prolonged parenteral nutrition. Nutrition 1992; 8:30.
  76. Orso G, Mandato C, Veropalumbo C, et al. Pediatric parenteral nutrition-associated liver disease and cholestasis: Novel advances in pathomechanisms-based prevention and treatment. Dig Liver Dis 2016; 48:215.
  77. O'Brien DP, Nelson LA, Kemp CJ, et al. Intestinal permeability and bacterial translocation are uncoupled after small bowel resection. J Pediatr Surg 2002; 37:390.
  78. Opilla MT, Kirby DF, Edmond MB. Use of ethanol lock therapy to reduce the incidence of catheter-related bloodstream infections in home parenteral nutrition patients. JPEN J Parenter Enteral Nutr 2007; 31:302.
  79. Jones BA, Hull MA, Richardson DS, et al. Efficacy of ethanol locks in reducing central venous catheter infections in pediatric patients with intestinal failure. J Pediatr Surg 2010; 45:1287.
  80. Oliveira C, Nasr A, Brindle M, Wales PW. Ethanol locks to prevent catheter-related bloodstream infections in parenteral nutrition: a meta-analysis. Pediatrics 2012; 129:318.
  81. Mouw E, Chessman K, Lesher A, Tagge E. Use of an ethanol lock to prevent catheter-related infections in children with short bowel syndrome. J Pediatr Surg 2008; 43:1025.
  82. Meehan JJ, Georgeson KE. Prevention of liver failure in parenteral nutrition-dependent children with short bowel syndrome. J Pediatr Surg 1997; 32:473.
  83. Sigalet D, Boctor D, Robertson M, et al. Improved outcomes in paediatric intestinal failure with aggressive prevention of liver disease. Eur J Pediatr Surg 2009; 19:348.
  84. Freund HR, Muggia-Sullam M, LaFrance R, et al. A possible beneficial effect of metronidazole in reducing TPN-associated liver function derangements. J Surg Res 1985; 38:356.
  85. Capron JP, Gineston JL, Herve MA, Braillon A. Metronidazole in prevention of cholestasis associated with total parenteral nutrition. Lancet 1983; 1:446.
  86. Ng PC, Lee CH, Wong SP, et al. High-dose oral erythromycin decreased the incidence of parenteral nutrition-associated cholestasis in preterm infants. Gastroenterology 2007; 132:1726.
  87. Spagnuolo MI, Iorio R, Vegnente A, Guarino A. Ursodeoxycholic acid for treatment of cholestasis in children on long-term total parenteral nutrition: a pilot study. Gastroenterology 1996; 111:716.
  88. Levine A, Maayan A, Shamir R, et al. Parenteral nutrition-associated cholestasis in preterm neonates: evaluation of ursodeoxycholic acid treatment. J Pediatr Endocrinol Metab 1999; 12:549.
  89. Chen CY, Tsao PN, Chen HL, et al. Ursodeoxycholic acid (UDCA) therapy in very-low-birth-weight infants with parenteral nutrition-associated cholestasis. J Pediatr 2004; 145:317.
  90. San Luis VA, Btaiche IF. Ursodiol in patients with parenteral nutrition-associated cholestasis. Ann Pharmacother 2007; 41:1867.
  91. Gleghorn EE, Merritt RJ, Subramanian N, Ramos A. Phenobarbital does not prevent total parenteral nutrition-associated cholestasis in noninfected neonates. JPEN J Parenter Enteral Nutr 1986; 10:282.
  92. Park HW, Lee NM, Kim JH, et al. Parenteral fish oil-containing lipid emulsions may reverse parenteral nutrition-associated cholestasis in neonates: a systematic review and meta-analysis. J Nutr 2015; 145:277.
  93. Lam HS, Tam YH, Poon TC, et al. A double-blind randomised controlled trial of fish oil-based versus soy-based lipid preparations in the treatment of infants with parenteral nutrition-associated cholestasis. Neonatology 2014; 105:290.
  94. Gura KM, Duggan CP, Collier SB, et al. Reversal of parenteral nutrition-associated liver disease in two infants with short bowel syndrome using parenteral fish oil: implications for future management. Pediatrics 2006; 118:e197.
  95. Gura KM, Lee S, Valim C, et al. Safety and efficacy of a fish-oil-based fat emulsion in the treatment of parenteral nutrition-associated liver disease. Pediatrics 2008; 121:e678.
  96. Diamond IR, Sterescu A, Pencharz PB, et al. Changing the paradigm: omegaven for the treatment of liver failure in pediatric short bowel syndrome. J Pediatr Gastroenterol Nutr 2009; 48:209.
  97. Puder M, Valim C, Meisel JA, et al. Parenteral fish oil improves outcomes in patients with parenteral nutrition-associated liver injury. Ann Surg 2009; 250:395.
  98. Premkumar MH, Carter BA, Hawthorne KM, et al. Fish oil-based lipid emulsions in the treatment of parenteral nutrition-associated liver disease: an ongoing positive experience. Adv Nutr 2014; 5:65.
  99. Calkins KL, Dunn JC, Shew SB, et al. Pediatric intestinal failure-associated liver disease is reversed with 6 months of intravenous fish oil. JPEN J Parenter Enteral Nutr 2014; 38:682.
  100. Le HD, de Meijer VE, Robinson EM, et al. Parenteral fish-oil-based lipid emulsion improves fatty acid profiles and lipids in parenteral nutrition-dependent children. Am J Clin Nutr 2011; 94:749.
  101. Soden JS, Lovell MA, Brown K, et al. Failure of resolution of portal fibrosis during omega-3 fatty acid lipid emulsion therapy in two patients with irreversible intestinal failure. J Pediatr 2010; 156:327.
  102. Dimmitt RA, Leadford Al, Bartle D, et al. Impact of omega-3 fatty acids on liver function test and liver histology in children with intestinal failure associated intestinal disease. Pediatric Academic Society Boston MA April 30,2012 E-PAS2012:3830.366
  103. Nandivada P, Chang MI, Potemkin AK, et al. The natural history of cirrhosis from parenteral nutrition-associated liver disease after resolution of cholestasis with parenteral fish oil therapy. Ann Surg 2015; 261:172.
  104. Nandivada P, Baker MA, Mitchell PD, et al. Predictors of failure of fish-oil therapy for intestinal failure-associated liver disease in children. Am J Clin Nutr 2016; 104:663.
  105. de Meijer VE, Le HD, Meisel JA, et al. Parenteral fish oil as monotherapy prevents essential fatty acid deficiency in parenteral nutrition-dependent patients. J Pediatr Gastroenterol Nutr 2010; 50:212.
  106. Nandivada P, Fell GL, Mitchell PD, et al. Long-Term Fish Oil Lipid Emulsion Use in Children With Intestinal Failure-Associated Liver Disease. JPEN J Parenter Enteral Nutr 2016.
  107. Vanek VW, Seidner DL, Allen P, et al. A.S.P.E.N. position paper: Clinical role for alternative intravenous fat emulsions. Nutr Clin Pract 2012; 27:150.
  108. Tomsits E, Pataki M, Tölgyesi A, et al. Safety and efficacy of a lipid emulsion containing a mixture of soybean oil, medium-chain triglycerides, olive oil, and fish oil: a randomised, double-blind clinical trial in premature infants requiring parenteral nutrition. J Pediatr Gastroenterol Nutr 2010; 51:514.
  109. Goulet O, Antébi H, Wolf C, et al. A new intravenous fat emulsion containing soybean oil, medium-chain triglycerides, olive oil, and fish oil: a single-center, double-blind randomized study on efficacy and safety in pediatric patients receiving home parenteral nutrition. JPEN J Parenter Enteral Nutr 2010; 34:485.
  110. Rayyan M, Devlieger H, Jochum F, Allegaert K. Short-term use of parenteral nutrition with a lipid emulsion containing a mixture of soybean oil, olive oil, medium-chain triglycerides, and fish oil: a randomized double-blind study in preterm infants. JPEN J Parenter Enteral Nutr 2012; 36:81S.
  111. Diamond IR, Grant RC, Pencharz PB, et al. Preventing the Progression of Intestinal Failure-Associated Liver Disease in Infants Using a Composite Lipid Emulsion: A Pilot Randomized Controlled Trial of SMOFlipid. JPEN J Parenter Enteral Nutr 2017; 41:866.
  112. Muhammed R, Bremner R, Protheroe S, et al. Resolution of parenteral nutrition-associated jaundice on changing from a soybean oil emulsion to a complex mixed-lipid emulsion. J Pediatr Gastroenterol Nutr 2012; 54:797.
  113. Lee S, Park HJ, Yoon J, et al. Reversal of Intestinal Failure-Associated Liver Disease by Switching From a Combination Lipid Emulsion Containing Fish Oil to Fish Oil Monotherapy. JPEN J Parenter Enteral Nutr 2016; 40:437.
  114. Hojsak I, Colomb V, Braegger C, et al. ESPGHAN Committee on Nutrition Position Paper. Intravenous Lipid Emulsions and Risk of Hepatotoxicity in Infants and Children: a Systematic Review and Meta-analysis. J Pediatr Gastroenterol Nutr 2016; 62:776.
  115. Finn KL, Chung M, Rothpletz-Puglia P, Byham-Gray L. Impact of Providing a Combination Lipid Emulsion Compared With a Standard Soybean Oil Lipid Emulsion in Children Receiving Parenteral Nutrition: A Systematic Review and Meta-Analysis. JPEN J Parenter Enteral Nutr 2015; 39:656.
  116. Cober MP, Killu G, Brattain A, et al. Intravenous fat emulsions reduction for patients with parenteral nutrition-associated liver disease. J Pediatr 2012; 160:421.
  117. Levit OL, Calkins KL, Gibson LC, et al. Low-Dose Intravenous Soybean Oil Emulsion for Prevention of Cholestasis in Preterm Neonates. JPEN J Parenter Enteral Nutr 2016; 40:374.
  118. Nehra D, Fallon EM, Carlson SJ, et al. Provision of a soy-based intravenous lipid emulsion at 1 g/kg/d does not prevent cholestasis in neonates. JPEN J Parenter Enteral Nutr 2013; 37:498.
  119. Cober MP, Teitelbaum DH. Prevention of parenteral nutrition-associated liver disease: lipid minimization. Curr Opin Organ Transplant 2010; 15:330.
  120. Teitelbaum DH, Han-Markey T, Drongowski RA, et al. Use of cholecystokinin to prevent the development of parenteral nutrition-associated cholestasis. JPEN J Parenter Enteral Nutr 1997; 21:100.
  121. Teitelbaum DH, Tracy TF Jr, Aouthmany MM, et al. Use of cholecystokinin-octapeptide for the prevention of parenteral nutrition-associated cholestasis. Pediatrics 2005; 115:1332.
  122. Mager DR, Marcon M, Wales P, Pencharz PB. Use of N-acetyl cysteine for the treatment of parenteral nutrition-induced liver disease in children receiving home parenteral nutrition. J Pediatr Gastroenterol Nutr 2008; 46:220.
  123. Becvarova I, Saker KE, Swecker WS Jr, Troy GC. Peroxidative protection of parenteral admixture by D-alpha-tocopherol. Vet Ther 2005; 6:280.
  124. Jensen AR, Goldin AB, Koopmeiners JS, et al. The association of cyclic parenteral nutrition and decreased incidence of cholestatic liver disease in patients with gastroschisis. J Pediatr Surg 2009; 44:183.