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Parenteral Nutrition-Associated Liver Disease in Pediatric Patients: Strategies for Treatment and Prevention

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Diseases of the Liver in Children

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Abstract

Parenteral nutrition (PN) has revolutionized the nutritional care of patients who cannot fully use the gastrointestinal tract. Today more than 30,000 patients, young and old, depend on long-term PN for survival, and more than 350,000 patients in the USA receive PN on a yearly basis. Despite its common usage, PN is associated with a number of significant morbidities. Parenteral nutrition-associated liver disease (PNALD) has become one of the most challenging complications associated with prolonged administration of PN. As PNALD progresses to a more permanent injury to the liver, patients are at high risk of additional morbidity and even mortality. A number of recognized risk factors have been attributed to PNALD, but it appears that no single factor is fully responsible as a causative agent or factor. Thus, the multifactorial nature of PNALD has been an incredible challenge to both clinicians and researchers, and the process unfortunately remains incompletely understood. This chapter discusses the current knowledge of PNALD, the potential causative factors, as well as treatment and preventive strategies.

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References

  1. Suita S, Yamanouchi T, Masumoto K, Ogita K, Nakamura M, Taguchi S. Changing profile of parenteral nutrition in pediatric surgery: a 30-year experience at one institute. Surgery. 2002;131(1 Suppl):S275–82. Epub 2002/02/01.

    Article  PubMed  Google Scholar 

  2. HCUPnet. National Center for Health Statistics Data on PN and EN Use. From the Agency for Healthcare Research and Quality (AHRQ). 2010. http://hcupnet.ahrq.gov/.

  3. Willis TC, Carter BA, Rogers SP, Hawthorne KM, Hicks PD, Abrams SA. High rates of mortality and morbidity occur in infants with parenteral nutrition-associated cholestasis. JPEN J Parenter Enteral Nutr. 2010;34(1):32–7. Epub 2009/07/10.

    Article  PubMed  Google Scholar 

  4. Teitelbaum DH, Drongowski R, Spivak D. Rapid development of hyperbilirubinemia in infants with the short bowel syndrome as a correlate to mortality: possible indication for early small bowel transplantation. Transplant Proc. 1996;28(5):2699–700.

    PubMed  CAS  Google Scholar 

  5. Btaiche IF, Khalidi N, Kovacevich DS, editors. The University of Michigan Hospital and Health Centers – parenteral and enteral nutrition manual. Ann Arbor: The University of Michigan; 2010.

    Google Scholar 

  6. Kelly DA. Liver complications of pediatric parenteral nutrition-epidemiology. Nutrition. 1998;14:153–7.

    Article  PubMed  CAS  Google Scholar 

  7. Koseesirikul P, Chotinaruemol S, Ukarapol N. Incidence and risk factors of PN-associated liver disease in newborn infants. Pediatr Int. 2012;54:434–6.

    Article  PubMed  Google Scholar 

  8. Duro D, Mitchell PD, Kalish LA, Martin C, McCarthy M, Jaksic T, et al. Risk factors for PN-associated liver disease following surgical therapy for necrotizing enterocolitis: a Glaser Pediatric Research Network Study. J Pediatr Gastroenterol Nutr. 2011;52:595–600.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Javid P, Malone FR, Dick AA, Hsu E, Sunseri M, Healey P, Horslen SP. A contemporary analysis of parenteral nutrition-associated liver disease in surgical infants. J Pediatr Surg. 2011;46(10):1913–7.

    Article  PubMed  Google Scholar 

  10. Nanji AA, Anderson FH. Sensitivity and specificity of liver function tests in the detection of parenteral nutrition associated cholestasis. J Parenter Enteral Nutr. 1985;9(3):307–8.

    Article  CAS  Google Scholar 

  11. Beath SV, Booth IW, Murphy MS, Buckels JA, Mayer AD, McKiernan PJ, Kelly DA. Nutritional care and candidates for small bowel transplantation. Arch Dis Child. 1995;73(4):348–50.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Naini BV, Lassman CR. Total parenteral nutrition therapy and liver injury: a histopathologic study with clinical correlation. Hum Pathol. 2012;43(6):826–33.

    Article  PubMed  CAS  Google Scholar 

  13. Beath SV, Needham SJ, Kelly DA, Booth IW, Raafat F, Buick RG, Buckels JA, Mayer AD. Clinical features and prognosis of children assessed for isolated small bowel or combined small bowel and liver transplantation. J Pediatr Surg. 1997;32(3):459–61.

    Article  PubMed  CAS  Google Scholar 

  14. Sax HC, Talamini MA, Brackett K, Fischer JE. Hepatic steatosis in total parenteral nutrition: failure of fatty infiltration to correlate with abnormal serum hepatic enzyme levels. Surgery. 1986;100(4):697–704.

    PubMed  CAS  Google Scholar 

  15. Btaiche IF, Khalidi N. Metabolic complications of parenteral nutrition in adults, part 2. Am J Health Syst Pharm. 2004;61(19):2050–9.

    PubMed  CAS  Google Scholar 

  16. Gurll NJ, Meyer PD, DenBesten L. The effect of cholesterol crystals on gallbladder function in cholelithiasis. Surg Forum. 1977;28:412–3.

    PubMed  CAS  Google Scholar 

  17. Allen B, Bernhoft R, Blanckaert N, Svanvik J, Filly R, Gooding G, Way L. Sludge is calcium bilirubinate associated with bile stasis. Am J Surg. 1981;141(1): 51–6.

    Article  PubMed  CAS  Google Scholar 

  18. King DR, Ginn-Pease ME, Lloyd TV, Hoffman J, Hohenbrink K. Parenteral nutrition with associated cholelithiasis: another iatrogenic disease of infants and children. J Pediatr Surg. 1987;22(7):593–6.

    Article  PubMed  CAS  Google Scholar 

  19. Tsai S, Strouse PJ, Drongowski RA, Islam S, Teitelbaum DH. Failure of cholecystokinin-octapeptide to prevent TPN-associated gallstone disease. J Pediatr Surg. 2005;40(1):263–7.

    Article  PubMed  Google Scholar 

  20. Hofmann AF. Defective biliary secretion during parenteral nutrition: probable mechanisms and possible solutions. J Pediatr Gastroenterol Nutr. 1995;20(4): 376–90.

    Article  PubMed  CAS  Google Scholar 

  21. Palmer RH, Ruban Z. Production of bile duct hyperplasia and gallstones by lithocholic acid. J Clin Invest. 1966;45(8):1255–67.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  22. Vileisis RA, Inwood RJ, Hunt CE. Laboratory monitoring of parenteral nutrition-associated hepatic dysfunction in infants. J Parenter Enteral Nutr. 1981;5(1):67–9.

    Article  CAS  Google Scholar 

  23. Btaiche IF, Khalidi N. Parenteral nutrition-associated liver complications in children. Pharmacotherapy. 2002;22(2):188–211.

    Article  PubMed  Google Scholar 

  24. Kurvinen A, Nissinen MJ, Gylling H, Miettinen TA, Lampela H, Koivusalo A, et al. Effects of long-term parenteral nutrition on serum lipids, plant sterols, cholesterol metabolism, and liver histology in pediatric intestinal failure. J Pediatr Gastroenterol Nutr. 2011;53(4):440–6.

    PubMed  CAS  Google Scholar 

  25. Ginn-Pease ME, Pantalos D, King DR. TPN-associated hyperbilirubinemia: a common problem in newborn surgical patients. J Pediatr Surg. 1985;20(4):436–9.

    Article  PubMed  CAS  Google Scholar 

  26. Spencer AU, Neaga A, West B, Safran J, Brown P, Btaiche I, et al. Pediatric short bowel syndrome: redefining predictors of success. Ann Surg. 2005;242(3):403–9; discussion 9–12. Epub 2005/09/02.

    PubMed  PubMed Central  Google Scholar 

  27. Rangel SJ, Calkins CM, Cowles RA, Barnhart DC, Huang EY, Abdullah F, et al. Parenteral nutrition–associated cholestasis: an American Pediatric Surgical Association Outcomes and Clinical Trials Committee systematic review. J Pediatr Surg. 2012;47(1):225–40.

    Article  PubMed  Google Scholar 

  28. Fallon EM, Mitchell PD, Potemkin AK, Nehra D, Arsenault DA, Robinson EM, et al. Cholestasis and growth in neonates with gastroschisis. J Pediatr Surg. 2012;47(8):1529–36.

    Article  PubMed  Google Scholar 

  29. Beale EF, Nelson RM, Bucciarelli RL, Donnelly WH, Eitzman DV. Intrahepatic cholestasis associated with parenteral nutrition in premature infants. Pediatrics. 1979;64(3):342–7.

    PubMed  CAS  Google Scholar 

  30. Pereira GR, Sherman MS, DiGiacomo J, Ziegler M, Roth K, Jacobowski D. Hyperalimentation-induced cholestasis: increase frequency and severity in premature infants. Am J Dis Child. 1981;135(9):842–5.

    Article  PubMed  CAS  Google Scholar 

  31. Beath SV, Davies P, Papadopoulou A, Khan AR, Buick RG, Corkery JJ, et al. Parenteral nutrition related cholestasis in postsurgical neonates: multivariate analysis of risk factors. J Pediatr Surg. 1996;31(4):604–6.

    Article  PubMed  CAS  Google Scholar 

  32. Moseley RH, Wang W, Takeda H, Lown K, Shick L, Ananthanarayanan M, et al. Effect of endotoxin on bile acid transport in rat liver: a potential model for sepsis-associated cholestasis. Am J Physiol. 1996;271(1 Pt 1):G137–46.

    PubMed  CAS  Google Scholar 

  33. Trauner M, Arrese M, Lee H, Boyer JL, Karpen SJ. Endotoxin downregulates rat hepatic ntcp gene expression via decreased activity of critical transcription factors. J Clin Invest. 1998;101(10):2092–100.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  34. Trauner M, Arrese M, Soroka CJ, Ananthanarayanan M, Koeppel TA, Schlosser SF, Suchy FJ, Keppler D, Boyer JL. The rat canalicular conjugate export pump (Mrp2) is down-regulated in intrahepatic and obstructive cholestasis. Gastroenterology. 1997;113(1):255–64.

    Article  PubMed  CAS  Google Scholar 

  35. Simmons MG, Georgeson KE, Figueroa R, Mock 2nd DL. Liver failure in parenteral nutrition dependent children with short bowel syndrome. Transplant Proc. 1996;28(5):2701.

    PubMed  CAS  Google Scholar 

  36. Stanko RT, Nathan G, Mendelow H, Adibi SA. Development of hepatic cholestasis and fibrosis with massive loss of intestine supported by prolonged parenteral nutrition. Gastroenterology. 1987;92(1):197–202.

    PubMed  CAS  Google Scholar 

  37. El Kasmi KC, Anderson AL, Devereaux MW, Fillon SA, Harris JK, Lovell MA, et al. Toll-like receptor 4-dependent Kupffer cell activation and liver injury in a novel mouse model of PN and intestinal injury. Hepatology. 2012;55(5):1518–28.

    Article  PubMed  CAS  Google Scholar 

  38. Colomb V, Goulet O, Rambaud C, De Potter S, Saddoun E, Ben-Hariz M, et al. Long-term parenteral nutrition in children: liver and gallbladder disease. Transplant Proc. 1992;24(3):1054–5.

    PubMed  CAS  Google Scholar 

  39. Kaufman SS, Loseke CA, Lupo JV, Young RJ, Murray ND, Pinch LW, Vanderhoof JA. Influence of bacterial overgrowth and intestinal inflammation on duration of parenteral nutrition in children with short bowel syndrome. J Pediatr. 1997;131(3):356–61.

    Article  PubMed  CAS  Google Scholar 

  40. Freund HR, Muggia-Sullam M, La France R, Enrione EB, Popp MB, Bjornson HS. A possible beneficial effect of metronidazole in reducing TPN-associated liver function derangements. J Surg Res. 1985;38(4):356–63.

    Article  PubMed  CAS  Google Scholar 

  41. Plaa GL, de Lamirande E, Lewittes M, Yousef IM. Liver cell plasma membrane lipids in manganese-bilirubin-induced intrahepatic cholestasis. Biochem Pharmacol. 1982;31(22):3698–701.

    Article  PubMed  CAS  Google Scholar 

  42. Fell JM, Reynolds AP, Meadows N, Khan K, Long SG, Quaghebeur G, Taylor WJ, Milla PJ. Manganese toxicity in children receiving long-term parenteral nutrition. Lancet. 1996;347(9010):1218–21.

    Article  PubMed  CAS  Google Scholar 

  43. Forbes A, Jawhari A. Manganese toxicity and parenteral nutrition [letter]. Lancet. 1996;347(9017):1774.

    Article  PubMed  CAS  Google Scholar 

  44. Jawhari A, Ong C, Wood S, Forbes A. Hypermanganesemia and TPN: a cause for cholestasis? Gastroenterology. 1995;108:A732.

    Article  Google Scholar 

  45. Howard L, Ashley C, Lyon D, Shenkin A. Autopsy tissue trace elements in 8 long-term parenteral nutrition patients who received the current U.S. Food and Drug Administration formulation. J Parenter Enteral Nutr. 2007;31(5):388–96.

    Article  CAS  Google Scholar 

  46. Blaszyk H, Wild PJ, Oliveira A, Kelly DG, Burgart LJ. Hepatic copper in patients receiving long-term parenteral nutrition. J Clin Gastroenterol. 2005;39(4):318–20.

    Article  PubMed  Google Scholar 

  47. Blackmer AB, Bailey E. Management of copper deficiency in cholestatic infants: review of the literature and a case series. Nutr Clin Pract. 2012;28(1):75–86. Epub ahead of print, 2012 Oct 15.

    Article  PubMed  Google Scholar 

  48. Department of Health and Human Services, Food and Drug Administration. Aluminum in large and small volume parenterals used in total parenteral nutrition. Fed Regist. 2000;(6):4103–11.

    Google Scholar 

  49. Alemmari A, Miller GG, Bertolo RF, Dinesh C, Brunton JA, Arnold CJ, Zello GA. Reduced aluminum contamination decreases parenteral nutrition associated liver injury. J Pediatr Surg. 2012;47(5):889–94.

    Article  PubMed  Google Scholar 

  50. Demircan M, Ergun O, Coker C, Yilmaz F, Avanoglu S, Ozok G. Aluminum in total parenteral nutrition solutions produces portal inflammation in rats. J Pediatr Gastroenterol Nutr. 1998;26(3):274–8.

    Article  PubMed  CAS  Google Scholar 

  51. Poole RL, Schiff L, Hintz SR, Wong A, Mackenzie N, Kerner Jr JA. Aluminum content of parenteral nutrition in neonates: measured versus calculated levels. J Pediatr Gastroenterol Nutr. 2010;50(2):208–11.

    Article  PubMed  CAS  Google Scholar 

  52. Ching YA, Gura K, Modi B, Jaksic T. Pediatric intestinal failure: nutrition, pharmacologic, and surgical approaches. Nutr Clin Pract. 2007;22(6):653–63.

    Article  PubMed  Google Scholar 

  53. Le HD, Fallon EM, de Meijer VE, Malkan AD, Puder M, Gura KM. Innovative parenteral and enteral nutrition therapy for intestinal failure. Semin Pediatr Surg. 2010;19(1):27–34.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Wessel JJ, Kocoshis SA. Nutritional management of infants with short bowel syndrome. Semin Perinatol. 2007;31(2):104–11.

    Article  PubMed  Google Scholar 

  55. Stout SM, Cober MP. Metabolic effects of cyclic parenteral nutrition infusion in adults and children. Nutr Clin Pract. 2010;25(3):277–81.

    Article  PubMed  Google Scholar 

  56. Jensen AR, Goldin AB, Koopmeiners JS, Stevens J, Waldhausen JH, Kima SS. The association of cyclic parenteral nutrition and decreased incidence of cholestatic liver disease in patients with gastroschisis. J Pediatr Surg. 2009;44(1):183–9.

    Article  PubMed  Google Scholar 

  57. Salvador A, Janeczko M, Porat R, Sekhon R, Moewes A, Schutzman D. Randomized controlled trial of early parenteral nutrition cycling to prevent cholestasis in very low birth weight infants. J Pediatr. 2012;161(2):229–33.

    Article  PubMed  Google Scholar 

  58. Friel C, Bistrian B. Cycled total parenteral nutrition: is it more effective? Am J Clin Nutr. 1997;65(4): 1078–9.

    PubMed  CAS  Google Scholar 

  59. Kumpf VJ. Parenteral nutrition-associated liver disease in adult and pediatric patients. Nutr Clin Pract. 2006;21(3):279–90.

    Article  PubMed  Google Scholar 

  60. Tillman EM. Review and clinical update on parenteral nutrition-associated liver disease. Nutr Clin Pract. 2013;28(1):30–9. Epub 2012 Oct 19.

    Article  PubMed  Google Scholar 

  61. Nehra D, Fallon EM, Carlson SJ, Potemkin AK, Hevelone ND, Mitchell PD, et al. Provision of soy-based intravenous lipid emulsions at 1 g/kg/day does not prevent cholestasis in neonates. J Parenter Enteral Nutr. 2013;37:498–505. [Epub ahead of print], PMID: 22767698.

    Article  Google Scholar 

  62. Kurvinen A, Nissinen MJ, Andersson S, Korhonen P, Ruuska T, Taimisto M, et al. Parenteral plant sterols and intestinal failure-associated liver disease in neonates. J Pediatr Gastroenterol Nutr. 2012;54(6):803–11.

    Article  PubMed  CAS  Google Scholar 

  63. Diamond IR, Pencharz PB, Feldman BM, Ling SC, Moore AM, Wales PW. Novel lipid based approaches to pediatric intestinal failure-associated liver disease. Arch Pediatr Adolesc Med. 2012;166(5):473–8.

    Article  PubMed  Google Scholar 

  64. Allardyce DB. Cholestasis caused by lipid emulsions. Surg Gynecol Obstet. 1982;154(5):641–7.

    PubMed  CAS  Google Scholar 

  65. Colomb V, Jobert-Giraud A, Lacaille F, Goulet O, Fournet J, Ricour C. Role of lipid emulsions in cholestasis associated with long-term parenteral nutrition in children. J Parenter Enteral Nutr. 2000;24(6):345–50.

    Article  CAS  Google Scholar 

  66. Cober MP, Killu G, Brattain A, Welch KB, Kunisaki SM, Teitelbaum DH. Intravenous fat emulsions reduction for patients with parenteral nutrition-associated liver disease. J Pediatr. 2012;160(3):421–7.

    Article  PubMed  CAS  Google Scholar 

  67. Cober MP, Teitelbaum DH. Prevention of parenteral nutrition-associated liver disease: lipid minimization. Curr Opin Organ Transplant. 2010;15(3):330–3.

    Article  PubMed  Google Scholar 

  68. Meisel JA, Le HD, de Meijer VE, Nose V, Gura KM, Mulkern RV, et al. Comparison of 5 intravenous lipid emulsions and their effects on hepatic steatosis in a murine model. J Pediatr Surg. 2011;46(4):666–73.

    Article  PubMed  Google Scholar 

  69. Gura KM, Duggan CP, Collier SB, Jennings RW, Folkman J, Bistrian BR, Puder M. 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(1):e197–201.

    Article  PubMed  Google Scholar 

  70. Jain SK, Pahwa M. Management of short gut syndrome by omega 3 fatty acid infusion. Clin Nutr. 2007;26(6):810.

    Article  PubMed  Google Scholar 

  71. Calhoun AW, Sullivan JE. Omegaven for the treatment of parenteral nutrition associated liver disease: a case study. J Ky Med Assoc. 2009;107(2):55–7.

    PubMed  Google Scholar 

  72. Cheung HM, Lam HS, Tam YH, Lee KH, Ng PC. Rescue treatment of infants with intestinal failure and parenteral nutrition-associated cholestasis (PNAC) using a parenteral fish-oil based lipid. Clin Nutr. 2009;28(2):209–12.

    Article  PubMed  CAS  Google Scholar 

  73. Chung PH, Wong KK, Wong RM, Tsoi NS, Chan KL, Tam PK. Clinical experience in managing pediatric patients with ultra-short bowel syndrome using omega-3 fatty acid. Eur J Pediatr Surg. 2010;20(2):139–42.

    Article  PubMed  CAS  Google Scholar 

  74. Pawlik D, Lauterback R, Turyk E. Fish-oil fat emulsion supplementation may reduce the risk of severe retinopathy in VLBW infants. Pediatrics. 2011;127(2):223–8.

    Article  PubMed  Google Scholar 

  75. Sigalet D, Boctor D, Brindle M, Lam V, Robertson M. Elements of successful intestinal rehabilitation. J Pediatr Surg. 2011;46(1):150–6.

    Article  PubMed  Google Scholar 

  76. Ekema G, Falchetti D, Boroni G, Tanca AR, Altana C, Righetti L, et al. Reversal of severe parenteral nutrition associated liver disease in an infant with short bowel syndrome using parenteral fish oil (omega-3 fatty acids). J Pediatr Surg. 2008;43(6):1191–5.

    Article  PubMed  Google Scholar 

  77. Puder M, Valim C, Meisel JA, Le HD, de Meijer VE, Robinson EM, et al. Parenteral fish oil improves outcomes in patients with parenteral nutrition-associated liver injury. Ann Surg. 2009;250(3):395–402.

    PubMed  PubMed Central  Google Scholar 

  78. Fallon EM, Le HD, Puder M. Prevention of parenteral nutrition-associated liver disease: role of omega-3 fish oil. Curr Opin Organ Transplant. 2010;15(3):334–40.

    Article  PubMed  Google Scholar 

  79. Diamond IR, Sterescu A, Pencharz PB, Kim JH, Wales PW. Changing the paradigm; Omegaven for the treatment of liver failure in pediatric short bowel syndrome. J Pediatr Gastroenterol Nutr. 2009;48(2):209–15.

    Article  PubMed  CAS  Google Scholar 

  80. Tillman EM, Crill CM, Black DD, Hak EB, Lazar LF, Christensen ML, et al. Enteral fish oil for treatment of parenteral nutrition-associated liver disease in six infants with short bowel syndrome. Pharmacotherapy. 2011;31(5):503–9.

    Article  PubMed  CAS  Google Scholar 

  81. Rollins MD, Scaife ER, Jackson WD, Meyers RL, Mulroy CW, Book LS. Elimination of soybean lipid emulsion in parenteral nutrition and supplementation with enteral fish oil improve cholestasis in infants with short bowel syndrome. Nutr Clin Pract. 2010;25(2):199–204.

    Article  PubMed  Google Scholar 

  82. Goulet O, Antebi H, Wolf C, Talbotec C, Alcindor LG, Corriol O, 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. J Parenter Enteral Nutr. 2010;34(5):485–95.

    Article  CAS  Google Scholar 

  83. Tomsits E, Pataki M, Tolgyesi A, Fekete G, Rischak K, Szollar L. Safety and efficacy of a lipid emulsion containing a mixture of soybean oil, olive oil, medium-chain triglycerides and fish oil: a randomized double-blind clinical trial in preterm infants requiring parenteral nutrition. J Pediatr Gastroenterol Nutr. 2010;51(4):514–21.

    Article  PubMed  CAS  Google Scholar 

  84. 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. J Parenter Enteral Nutr. 2012;36(1 Suppl):81S–94.

    Article  CAS  Google Scholar 

  85. Skouroliakou M, Konstantinou D, Koutri K, Kakavelaki C, Stathopoulou M, Antonidai M, et al. A double-blind, randomized clinical trial of the effect of omega-3 fatty acids on the oxidative stress of preterm neonates fed through parenteral nutrition. Eur J Clin Nutr. 2010;64(9):940–7.

    Article  PubMed  CAS  Google Scholar 

  86. Muhammed R, Bremner R, Protheroe S, Johnson T, Holden C, Murphy MS. Resolution of parenteral nutrition associated jaundice on changing from a soy-oil emulsion to a complex mixed-lipid emulsion. J Pediatr Gastroenterol Nutr. 2012;54(6):797–802.

    Article  PubMed  CAS  Google Scholar 

  87. Ferreira N, Falconer J, Harley C, Rawat D, Fell J, Koglmeier J. Improved serum bilirubin with SMOF lipid in children with intestinal failure on long term parenteral nutrition. Paper presented at: British Society of Paediatric Gastroenterology, Hepatology and Nutrition Winter Meeting, Sheffield; 28–30 Jan 2009.

    Google Scholar 

  88. Anish A, Lawson A, Cram H, et al. SMOF lipid in intestinal failure associated liver disease: experience in a regional centre. Paper presented at: British Society of Paediatric Gastroenterology, Hepatology and Nutrition Winter Meeting, Liverpool; 27–29 Jan 2010.

    Google Scholar 

  89. Vanek VW, Seidner DL, Allen P, Bistrian B, Collier S, Gura K, et al. A.S.P.E.N. position paper: clinical role for alternative intravenous fat emulsions. Nutr Clin Pract. 2012;27(2):150–92. Epub 2012 Feb 29.

    Article  PubMed  Google Scholar 

  90. Phenobarbital. Lexi-Comp OnlineTM, Pediatric & Neonatal Lexi-Drugs OnlineTM. Hudson: Lexi-Comp, Inc.; 2013.

    Google Scholar 

  91. Berger HM. Phenobarbital therapy and parenteral nutrition. J Parenter Enteral Nutr. 1987;11(3):331.

    Article  CAS  Google Scholar 

  92. Gleghorn EE, Merritt RJ, Subramanian N, Ramos A. Phenobarbital does not prevent total parenteral nutrition-associated cholestasis in noninfected neonates. J Parenter Enteral Nutr. 1986;10(3):282–3.

    Article  CAS  Google Scholar 

  93. South M, King A. Parenteral nutrition-associated cholestasis: recovery following phenobarbitone. J Parenter Enteral Nutr. 1987;11(2):208–9.

    CAS  Google Scholar 

  94. San Luis VA, Btaiche IF. Ursodiol in patients with parenteral nutrition-associated cholestasis. Ann Pharmacother. 2007;41(11):1867–72.

    Article  PubMed  CAS  Google Scholar 

  95. Trauner M, Graziadei IW. Review article: mechanisms of action and therapeutic applications of ursodeoxycholic acid in chronic liver diseases. Aliment Pharmacol Ther. 1999;13(8):979–96.

    Article  PubMed  CAS  Google Scholar 

  96. Ursodiol. Lexi-Comp OnlineTM, Pediatric & Neonatal Lexi-Drugs OnlineTM. Hudson: Lexi-Comp, Inc.; 2013.

    Google Scholar 

  97. Kumar D, Tandon RK. Use of ursodeoxycholic acid in liver disease. J Gastroenterol Hepatol. 2001;16(1):3–14.

    Article  PubMed  CAS  Google Scholar 

  98. Angulo P. Use of ursodeoxycholic acid in patients with liver disease. Curr Gastroenterol Rep. 2002;4(1):37–44.

    Article  PubMed  Google Scholar 

  99. Lebensztejn DM. Application of ursodeoxycholic acid (UDCA) in the therapy of liver and biliary duct disease in children. Med Sci Monit. 2000;6(3):632–6.

    PubMed  CAS  Google Scholar 

  100. Kowdley KV. Ursodeoxycholic acid therapy in hepatobiliary disease. Am J Med. 2000;108(6):481–6.

    Article  PubMed  CAS  Google Scholar 

  101. Chen CY, Tsao PN, Chen HL, Chou HC, Hsieh WS, Chang MH. Ursodeoxycholic acid (UDCA) therapy in very-low-birth-weight infants with parenteral nutrition-associated cholestasis. J Pediatr. 2004;145(3): 317–21.

    Article  PubMed  CAS  Google Scholar 

  102. Al-Hathlol K, Al-Madani A, Al-Saif S, Abulaimoun B, Al-Tawil K, El-Demerdash A. Ursodeoxycholic acid therapy for intractable total parenteral nutrition-associated cholestasis in surgical very low birth weight infants. Singapore Med J. 2006;47(2):147–51.

    PubMed  CAS  Google Scholar 

  103. Levine A, Maayan A, Shamir R, Dinari G, Sulkes J, Sirotta L. Parenteral nutrition-associated cholestasis in preterm neonates: evaluation of ursodeoxycholic acid treatment. J Pediatr Endocrinol Metab. 1999;12(4):549–53.

    Article  PubMed  CAS  Google Scholar 

  104. 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(3):716–9.

    Article  PubMed  CAS  Google Scholar 

  105. De Marco G, Sordion D, Bruzzese E, Di Caro S, Mambretti D, Tramontano A, et al. Early treatment with ursodeoxycholic acid for cholestasis in children on parenteral nutrition because of primary intestinal failure. Aliment Pharmacol Ther. 2006;24(2):387–94.

    Article  PubMed  CAS  Google Scholar 

  106. Heubi JE, Wiechmann DA, Creutzinger V, Setchell KD, Squires Jr R, Couser R, et al. Tauroursodeoxycholic acid (TUDCA) in the prevention of total parenteral nutrition-associated liver disease. J Pediatr. 2002;141(2):237–42.

    Article  PubMed  CAS  Google Scholar 

  107. Teitelbaum DH, Han-Markey T, Schumacher RE. Treatment of parenteral nutrition-associated cholestasis with cholecystokinin-octapeptide. J Pediatr Surg. 1995;30(7):1082–5.

    Article  PubMed  CAS  Google Scholar 

  108. Rintala RJ, Lindahl H, Pohjavuori M. Total parenteral nutrition-associated cholestasis in surgical neonates may be reversed by intravenous cholecystokinin: a preliminary report. J Pediatr Surg. 1995;30(6):827–30.

    Article  PubMed  CAS  Google Scholar 

  109. Teitelbaum DH, Han-Markey T, Drongowski R, Coran AG, Bayar B, Geiger JD, et al. Use of cholecystokinin to prevent the development of parenteral nutrition-associated cholestasis. J Parenter Enteral Nutr. 1997;21(2):100–3.

    Article  CAS  Google Scholar 

  110. Teitelbaum DH, Tracey Jr TF, Aouthmany MM, Llanos A, Brown MB, Yu S, et al. Use of cholecystokinin-octapeptide for the prevention of parenteral nutrition-associated cholestasis. Pediatrics. 2005;115(5):1332–40.

    Article  PubMed  Google Scholar 

  111. Wang Y, Tao YX, Cai W, Tang QY, Feng Y, Wu J. Protective effect of parenteral glutamine supplementation on hepatic function in very low birth weight infants. Clin Nutr. 2010;29(3):307–11.

    Article  PubMed  CAS  Google Scholar 

  112. Helms RA, Storm MC, Christensen ML, Hak EB, Chesney RW. Cysteine supplementation results in normalization of plasma taurine concentrations in children receiving home parenteral nutrition. J Pediatr. 1999;134(3):358–61.

    Article  PubMed  CAS  Google Scholar 

  113. Spencer AU, Yu S, Tracey TF, Aouthmany MM, Llanos A, Brown MB, et al. Parenteral nutrition–associated cholestasis in neonates: multivariate analysis of the potential protective effect of taurine. J Parenter Enteral Nutr. 2005;29(5):337–44.

    Article  CAS  Google Scholar 

  114. 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(2):318–29.

    Article  PubMed  Google Scholar 

  115. Dobson R, McGuckin C, Walker G, Lucas C, McGrogan P, Russell RK, et al. Cycled enteral antibiotics reduce sepsis rates in paediatric patients on long-term parenteral nutrition for intestinal failure. Aliment Pharmacol Ther. 2011;34(8):1005–11.

    Article  PubMed  CAS  Google Scholar 

  116. Kubota A, Okada A, Imura K, Kawahara H, Nezu R, Kamata S, et al. The effect of metronidazole on TPN-associated liver dysfunction in neonates. J Pediatr Surg. 1990;25(6):618–21.

    Article  PubMed  CAS  Google Scholar 

  117. Pierro A, van Saene HK, Jones MO, Brown D, Nunn AJ, Lloyd DA. Clinical impact of abnormal gut flora in infants receiving parenteral nutrition. Ann Surg. 1998;227(4):547–52.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  118. National Nosocomial Infections Surveillance System. National nosocomial infections surveillance (NNIS) system report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control. 2004;32(8):470–85.

    Article  Google Scholar 

  119. Bagnall-Reeb H. Evidence for the use of the antibiotic lock technique. J Infus Nurs. 2004;27(2):118–22.

    Article  PubMed  Google Scholar 

  120. Onder AM, Kato T, Simon N, Rivera-Hernandez M, Chandar J, Montane B, et al. Prevention of catheter-related bacteremia in pediatric intestinal transplantation/short gut syndrome children with long-term central venous catheters. Pediatr Transplant. 2007;11(1):87–93.

    Article  PubMed  Google Scholar 

  121. Bestul MB, Vandenbussche HL. Antibiotic lock technique: review of the literature. Pharmacotherapy. 2005;25(2):211–27.

    Article  PubMed  CAS  Google Scholar 

  122. Mermel LA, Allon M, Bouza E, Craven DE, Flynn P, O’Grady NP, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the infectious diseases society of America. Clin Infect Dis. 2009;49(1):1–45.

    Article  PubMed  CAS  Google Scholar 

  123. Ball PA, Brokenshire E, Parry B, Merrie A, Gillanders L, McIllroy K, Plank L. Ethanol locking as a possible treatment for microbial contamination of long-term central venous catheters. Nutrition. 2003;19(6):570.

    Article  PubMed  Google Scholar 

  124. Dannenberg C, Bierbach U, Rothe A, Beer J, Korholz D. Ethanol-lock technique in the treatment of bloodstream infections in pediatric oncology patients with broviac catheter. J Pediatr Hematol Oncol. 2003;25(8):616–21.

    Article  PubMed  Google Scholar 

  125. Jones BA, Hull MA, Richardson DS, Zurakowski D, Gura K, Fitzgibbons SC, et al. Efficacy of ethanol locks in reducing central venous catheter infections in pediatric patients with intestinal failure. J Pediatr Surg. 2010;45(6):1287–93.

    Article  PubMed  Google Scholar 

  126. 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(6):1025–9.

    Article  PubMed  Google Scholar 

  127. Cober MP, Kovacevich DS, Teitelbaum DH. Ethanol-lock therapy for the prevention of central venous access device infections in pediatric patients with intestinal failure. J Parenter Enteral Nutr. 2011;35(1):67–73.

    Article  Google Scholar 

  128. Wales PW, Kosar C, Carricato M, de Silva N, Lang K, Avitzur Y. Ethanol lock therapy to reduce the incidence of catheter-related bloodstream infections in home parenteral nutrition patients with intestinal failure: preliminary experience. J Pediatr Surg. 2011;46(5):951–6.

    Article  PubMed  Google Scholar 

  129. Wong T, Clifford V, McCallum Z, Shalley H, Peterkin M, Paxton G, et al. Central venous catheter thrombosis associated with 70% ethanol locks in pediatric intestinal failure patients on home parenteral nutrition: a case series. J Parenter Enteral Nutr. 2012;36(3):358–60.

    Article  Google Scholar 

  130. Cober MP, Johnson CE. Stability of 70% alcohol solutions in polypropylene syringes for use in ethanol-lock therapy. Am J Health Syst Pharm. 2007;64(23):2480–2.

    Article  PubMed  CAS  Google Scholar 

  131. Ralls MW, Blackwood RA, Arnold MA, Partipilo ML, Dimond J, Teitelbaum DH. Drug shortage-associated increase in catheter related blood stream infection in children. Pediatrics. 2012;130(5):e1369–73.

    Article  PubMed  Google Scholar 

  132. Goulet OJ, Revillon Y, Jan D, De Potter S, Maurage C, Lortat-Jacob S, et al. Neonatal short bowel syndrome. J Pediatr. 1991;119(1 Pt 1):18–23. Epub 1991/07/01.

    Article  PubMed  CAS  Google Scholar 

  133. Barksdale EM, Stanford A. The surgical management of short bowel syndrome. Curr Gastroenterol Rep. 2002;4(3):229–37. Epub 2002/05/16.

    Article  PubMed  Google Scholar 

  134. Andorsky DJ, Lund DP, Lillehei CW, Jaksic T, Dicanzio J, Richardson DS, et al. Nutritional and other postoperative management of neonates with short bowel syndrome correlates with clinical outcomes. J Pediatr. 2001;139(1):27–33. Epub 2001/07/11.

    Article  PubMed  CAS  Google Scholar 

  135. Gertler JP, Seashore JH, Touloukian RJ. Early ileostomy closure in necrotizing enterocolitis. J Pediatr Surg. 1987;22(2):140–3. Epub 1987/02/01.

    Article  PubMed  CAS  Google Scholar 

  136. Chaet MS, Farrell MK, Ziegler MM, Warner BW. Intensive nutritional support and remedial surgical intervention for extreme short bowel syndrome. J Pediatr Gastroenterol Nutr. 1994;19(3):295–8. Epub 1994/10/01.

    Article  PubMed  CAS  Google Scholar 

  137. Diamanti A, Basso MS, Castro M, Calce A, Pietrobattista A, Gambarara M. Prevalence of life-threatening complications in pediatric patients affected by intestinal failure. Transplant Proc. 2007;39(5):1632–3. Epub 2007/06/21.

    Article  PubMed  CAS  Google Scholar 

  138. Venables CW, Ellis H, Smith AD. Antiperistaltic segments after massive intestinal resections. Lancet. 1966;2(7478):1390–4. Epub 1966/12/24.

    Article  PubMed  CAS  Google Scholar 

  139. Altman DP, Ellison EH. Massive intestinal resection: inadequacies of the recirculating loop. Surg Forum. 1965;16:365–7. Epub 1965/01/01.

    PubMed  CAS  Google Scholar 

  140. Hutcher NE, Salzberg AM. Pre-ileal transposition of colon to prevent the development of short bowel syndrome in puppies with 90 percent small intestinal resection. Surgery. 1971;70(2):189–97. Epub 1971/08/01.

    PubMed  CAS  Google Scholar 

  141. de Lorimier AA, Harrison MR. Intestinal plication in the treatment of atresia. J Pediatr Surg. 1983;18(6):734–7. Epub 1983/12/01.

    Article  PubMed  Google Scholar 

  142. Priebe Jr CJ. Reversed intestinal segments in young puppies with massive intestinal resections. J Pediatr Surg. 1970;5(2):215–23. Epub 1970/04/01.

    Article  PubMed  Google Scholar 

  143. Warner B, Chaet M. Nontransplant surgical options for management of the short bowel syndrome. J Pediatr Gastroenterol Nutr. 1993;17(1):1–12.

    Article  PubMed  CAS  Google Scholar 

  144. Muraki T, Singleton AO Jr. Effects of recirculating jejunal loops on absorption and transit after massive bowel resection in dogs. Surg Forum. 1964;15:291–2. PMID:14189373.

    Google Scholar 

  145. Hutcher NE, Mendez-Picon G, Salzberg AM. Prejejunal transposition of colon to prevent the development of short bowel syndrome in puppies with 90 per cent small intestine resection. J Pediatr Surg. 1973;8(5):771–7. Epub 1973/10/01.

    Article  PubMed  CAS  Google Scholar 

  146. Garcia VF, Templeton JM, Eichelberger MR, Koop CE, Vinograd I. Colon interposition for the short bowel syndrome. J Pediatr Surg. 1981;16(6):994–5. Epub 1981/12/01.

    Article  PubMed  CAS  Google Scholar 

  147. Glick PL, de Lorimier AA, Adzick NS, Harrison MR. Colon interposition: an adjuvant operation for short-gut syndrome. J Pediatr Surg. 1984;19(6):719–25. Epub 1984/12/01.

    Article  PubMed  CAS  Google Scholar 

  148. Devesa JM, Botella-Carretero JI, Lopez Hervas P, Rey A, Die J, Calero A. Ultrashort bowel syndrome: surgical management and long-term results of an exceptional case. J Pediatr Surg. 2008;43(3):E5–9. Epub 2008/03/25.

    Article  PubMed  Google Scholar 

  149. Sudan D, DiBaise J, Torres C, Thompson J, Raynor S, Gilroy R, et al. A multidisciplinary approach to the treatment of intestinal failure. J Gastrointest Surg. 2005;9(2):165–76; discussion 76–7. Epub 2005/02/08.

    Article  PubMed  Google Scholar 

  150. Jones BA, Hull MA, McGuire MM, Kim HB. Autologous intestinal reconstruction surgery. Semin Pediatr Surg. 2010;19(1):59–67. Epub 2010/02/04.

    Article  PubMed  Google Scholar 

  151. Nayyar N, Mazariegos G, Ranganathan S, Soltys K, Bond G, Jaffe R, et al. Pediatric small bowel transplantation. Semin Pediatr Surg. 2010;19(1):68–77. Epub 2010/02/04.

    Article  PubMed  Google Scholar 

  152. Bianchi A. Intestinal loop lengthening – a technique for increasing small intestinal length. J Pediatr Surg. 1980;15(2):145–51. Epub 1980/04/01.

    Article  PubMed  CAS  Google Scholar 

  153. Chahine AA, Ricketts RR. A modification of the Bianchi intestinal lengthening procedure with a single anastomosis. J Pediatr Surg. 1998;33(8):1292–3. Epub 1998/08/29.

    Article  PubMed  CAS  Google Scholar 

  154. Ehrlich PF, Mychaliska GB, Teitelbaum DH. The 2 STEP: an approach to repeating a serial transverse enteroplasty. J Pediatr Surg. 2007;42(5):819–22. Epub 2007/05/16.

    Article  PubMed  Google Scholar 

  155. Thompson JS, Pinch LW, Young R, Vanderhoof JA. Long-term outcome of intestinal lengthening. Transplant Proc. 2000;32(6):1242–3. Epub 2000/09/21.

    Article  PubMed  CAS  Google Scholar 

  156. Waag KL, Hosie S, Wessel L. What do children look like after longitudinal intestinal lengthening. Eur J Pediatr Surg. 1999;9(4):260–2. Epub 1999/10/26.

    Article  PubMed  CAS  Google Scholar 

  157. Bianchi A. From the cradle to enteral autonomy: the role of autologous gastrointestinal reconstruction. Gastroenterology. 2006;130(2 Suppl 1):S138–46. Epub 2006/02/14.

    Article  PubMed  Google Scholar 

  158. Kim HB, Fauza D, Garza J, Oh JT, Nurko S, Jaksic T. Serial transverse enteroplasty (STEP): a novel bowel lengthening procedure. J Pediatr Surg. 2003;38(3):425–9.

    Article  PubMed  Google Scholar 

  159. Ching YA, Fitzgibbons S, Valim C, Zhou J, Duggan C, Jaksic T, et al. Long-term nutritional and clinical outcomes after serial transverse enteroplasty at a single institution. J Pediatr Surg. 2009;44(5):939–43. Epub 2009/05/13.

    Article  PubMed  PubMed Central  Google Scholar 

  160. Modi BP, Javid PJ, Jaksic T, Piper H, Langer M, Duggan C, et al. First report of the international serial transverse enteroplasty data registry: indications, efficacy, and complications. J Am Coll Surg. 2007;204(3):365–71. Epub 2007/02/28.

    Article  PubMed  PubMed Central  Google Scholar 

  161. Piper H, Modi BP, Kim HB, Fauza D, Glickman J, Jaksic T. The second STEP: the feasibility of repeat serial transverse enteroplasty. J Pediatr Surg. 2006;41(12):1951–6. Epub 2006/12/13.

    Article  PubMed  Google Scholar 

  162. Andres AM, Thompson J, Grant W, Botha J, Sunderman B, Antonson D, et al. Repeat surgical bowel lengthening with the STEP procedure. Transplantation. 2008;85(9):1294–9. Epub 2008/05/14.

    Article  PubMed  Google Scholar 

  163. Duggan C, Piper H, Javid PJ, Valim C, Collier S, Kim HB, et al. Growth and nutritional status in infants with short-bowel syndrome after the serial transverse enteroplasty procedure. Clin Gastroenterol Hepatol. 2006;4(10):1237–41. Epub 2006/08/15.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical, Social and Administrative Sciences, The University of Michigan College of Pharmacy, 428 Church Street, Ann Arbor, MI, 48109, USA

    Allison Beck Blackmer PharmD, BCPS

  2. School of Pharmacy, Lebanese American University, 36, Byblos, Lebanon

    Imad F. Btaiche PharmD, BCNSP

  3. Department of Pediatric Surgery, The University of Michigan, C.S. Mott Children’s Hospital, 1540 East Hospital Drive, Room 4-962, Ann Arbor, MI, 48109, USA

    Meghan A. Arnold MD

  4. Division of Pediatric Surgery, Department of Surgery, University of Michigan, C.S. Mott Children’s Hospital, 1540 East Hospital Drive, Room 4-962, Ann Arbor, MI, 48109, USA

    Daniel H. Teitelbaum MD

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  1. Allison Beck Blackmer PharmD, BCPS
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  2. Imad F. Btaiche PharmD, BCNSP
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  3. Meghan A. Arnold MD
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  4. Daniel H. Teitelbaum MD
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Correspondence to Daniel H. Teitelbaum MD .

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  1. University of Washington School of Medicine, Seattle Children’s Hospital, Seattle, Washington, USA

    Karen F. Murray

  2. University of Washington School of Medicine, Seattle Children’s Hospital, Seattle, Washington, USA

    Simon Horslen

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Blackmer, A.B., Btaiche, I.F., Arnold, M.A., Teitelbaum, D.H. (2014). Parenteral Nutrition-Associated Liver Disease in Pediatric Patients: Strategies for Treatment and Prevention. In: Murray, K., Horslen, S. (eds) Diseases of the Liver in Children. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9005-0_17

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