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Clinical nutrition

Effect of a fish oil-based lipid emulsion on intestinal failure-associated liver disease in children

European Journal of Clinical Nutrition volume 72, pages 1364–1372 (2018)Cite this article

Subjects

Abstract

Background/Objectives

The aim of this study was to assess the effects of a fish oil-based lipid emulsion on intestinal failure-associated liver disease (IFALD) in children.

Subjects/Methods

From January 2014 through June 2017, we enrolled 32 children with IF on long-term parenteral nutrition (PN). When the levels of any three of seven liver indicators (TBA, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, gamma glutamyl transferase (γ-GT), total bilirubin (TB), or direct bilirubin (DB)) were two times higher than normal levels, we switched a 50:50 mix of soybean oil and medium-chain triglycerides (MCT) lipid emulsion (with an average dose of 1.30 g/kg/day) to a fish oil-based lipid emulsion (1 g/kg/day) and measured liver function in the children. Meanwhile, inflammation and oxidative stress-related markers were also measured.

Results

The average fish oil therapy duration was 26 ± 21 days, and the median duration of PN support was 84 days. With fish oil therapy, levels of TBA, ALT, AST, γ-GT, TB, and DB all significantly decreased. Enteral nutrition was introduced following fish oil resulting in higher energy intake (99.88 ± 31.06 kcal/kg/day) compared with before fish oil (67.90 ± 27.31 kcal/kg/day, P = 0.001). No significant difference was found in average PN energy (P = 0.147). In addition, levels of inflammatory indicators like tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), and white blood cell (WBC) significantly decreased.

Conclusions

Fish oil therapy alleviates IFALD in children.

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References

  1. Pironi L, Arends J, Bozzetti F, Cuerda C, Gillanders L, Jeppesen PB. et al. ESPEN guidelines on chronic intestinal failure in adults. Clin Nutr. 2016;35:247–307. https://doi.org/10.1016/j.clnu.2016.01.020

    Article  PubMed  Google Scholar 

  2. Goulet O, Lambe C. Intravenous lipid emulsions in pediatric patients with intestinal failure. Curr Opin Organ Transplant. 2017;22:142–8. https://doi.org/10.1097/MOT.0000000000000396

    Article  CAS  PubMed  Google Scholar 

  3. Willis T, Carter B, Rogers S, Hawthorne K, Hicks P, Abrams S. High rates of mortality and morbidity occur in infants with parenteral nutrition-associated cholestasis. JPEN J Parenter Enter Nutr. 2010;34:32–7.

    Article  Google Scholar 

  4. Vlaardingerbroek H, van Goudoever J. Intravenous lipids in preterm infants: impact on laboratory and clinical outcomes and long-term consequences. World Rev Nutr Diet. 2015;112:71–80.

    Article  Google Scholar 

  5. Cavicchi M, Beau P, Crenn P, Degott C, Messing B. Prevalence of liver disease and contributing factors in patients receiving home parenteral nutrition for permanent intestinal failure. Ann Intern Med. 2000;132:525–32.

    Article  CAS  Google Scholar 

  6. Burrin D, Ng K, Stoll B, Sáenz De, Pipaón M. Impact of new-generation lipid emulsions on cellular mechanisms of parenteral nutrition-associated liver disease. Adv Nutr. 2014;5:82–91.

    Article  CAS  Google Scholar 

  7. Gura KM, Lee S, Valim C, Zhou J, Kim S, Modi BP. et al. Safety and efficacy of a fish-oil-based fat emulsion in the treatment of parenteral nutrition-associated liver disease. Pediatrics. 2008;121:e678–86. https://doi.org/10.1542/peds.2007-2248

    Article  PubMed  Google Scholar 

  8. Lin M, Hsu C, Yeh S, Yeh C, Chang K, Lee P, et al. Effects of omega-3 fatty acids on leukocyte Th1/Th2 cytokine and integrin expression in rats with gut-derived sepsis. Nutrition. 2007;23:179–86.

    Article  CAS  Google Scholar 

  9. Goulet O, Antébi H, Wolf C, Talbotec C, Alcindor L, 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. JPEN J Parenter Enter Nutr. 2010;34:485–95.

    Article  CAS  Google Scholar 

  10. Javid PJ, Malone FR, Dick AA, Hsu E, Sunseri M, Healey P. et al. A contemporary analysis of parenteral nutrition-associated liver disease in surgical infants. J Pediatr Surg. 2011;46:1913–7. https://doi.org/10.1016/j.jpedsurg.2011.06.002

    Article  PubMed  Google Scholar 

  11. Badia-Tahull MB, Llop-Talaveron J, Leiva-Badosa E. Impact of intravenous lipid emulsions on liver function tests: contribution of parenteral fish oil. Nutrition. 2015;31:1109–16. https://doi.org/10.1016/j.nut.2015.04.005

    Article  CAS  PubMed  Google Scholar 

  12. Gong Y, Liu Z, Liao Y, Mai C, Chen T, Tang H et al. Effectiveness of omega-3 polyunsaturated fatty acids based lipid emulsions for treatment of patients after hepatectomy: a prospective clinical trial. Nutrients. 2016; 8. https://doi.org/10.3390/nu8060357

    Article  Google Scholar 

  13. Badia-Tahull MB, Leiva-Badosa E, Jodar-Masanes R, Ramon-Torrell JM, Llop-Talaveron J. The relationship between the parenteral dose of fish oil supplementation and the variation of liver function tests in hospitalized adult patients. Nutr J. 2015;14:65. https://doi.org/10.1186/s12937-015-0048-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mao G, Wang Y, Qiu Q, Deng H, Yuan L, Li R, et al. Salidroside protects human fibroblast cells from premature senescence induced by H(2)O(2) partly through modulating oxidative status. Mech Ageing Dev. 2010;131:723–31.

    Article  CAS  Google Scholar 

  15. Bharadwaj S, Tandon P, Meka K, Rivas JM, Jevenn A, Kuo NT. et al. Intestinal failure: adaptation, rehabilitation, and transplantation. J Clin Gastroenterol. 2016;50:366–72.

    PubMed  Google Scholar 

  16. Pironi L. Definitions of intestinal failure and the short bowel syndrome. Best Pract Res Clin Gastroenterol. 2016;30:173–85.

    Article  Google Scholar 

  17. Kelly DA. Intestinal failure-associated liver disease: what do we know today?. Gastroenterology. 2006;130(Suppl. 1):S70–7. https://doi.org/10.1053/j.gastro.2005.10.066

    Article  CAS  PubMed  Google Scholar 

  18. Gura KM, Duggan CP, Collier SB, Jennings RW, Folkman J, Bistrian BR. 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:e197–201. https://doi.org/10.1542/peds.2005-2662

    Article  PubMed  Google Scholar 

  19. Sorrell M, Moreira A, Green K, Jacob R, Tragus R, Keller L. et al. Favorable outcomes of preterm infants with parenteral nutrition-associated liver disease treated with intravenous fish oil-based lipid emulsion. J Pediatr Gastroenterol Nutr. 2017;64:783–8. https://doi.org/10.1097/mpg.0000000000001397

    Article  CAS  PubMed  Google Scholar 

  20. Park HW, Lee NM, Kim JH, Kim KS, Kim SN. Parenteral fish oil-containing lipid emulsions may reverse parenteral nutrition-associated cholestasis in neonates: a systematic review and meta-analysis. J Nutr. 2015;145:277–83. https://doi.org/10.3945/jn.114.204974

    Article  CAS  PubMed  Google Scholar 

  21. Edward RR, Innes JK, Marino LV, Calder PC. Influence of different intravenous lipid emulsions on growth, development and laboratory and clinical outcomes in hospitalised paediatric patients: a systematic review. Clin Nutr. 2017. https://doi.org/10.1016/j.clnu.2017.07.003

    Article  PubMed  Google Scholar 

  22. Nandivada P, Fell G, Mitchell P, Potemkin A, O’Loughlin A, Gura K, et al. Long-term fish oil lipid emulsion use in children with intestinal failure-associated liver disease [formula: see text]. JPEN J Parenter Enter Nutr. 2017;41:930–7.

    Article  CAS  Google Scholar 

  23. Manzanares W, Langlois PL, Lemieux M, Heyland DK. Fish oil-containing emulsions: when fat seems to improve clinical outcomes in the critically ill. JPEN J Parenter Enter Nutr. 2016;40:305–7. https://doi.org/10.1177/0148607115586263

    Article  CAS  Google Scholar 

  24. Manzanares W, Langlois PL, Dhaliwal R, Lemieux M, Heyland DK. Intravenous fish oil lipid emulsions in critically ill patients: an updated systematic review and meta-analysis. Crit Care. 2015;19:167. https://doi.org/10.1186/s13054-015-0888-7

    Article  PubMed  PubMed Central  Google Scholar 

  25. Beghin L, Storme L, Coopman S, Rakza T, Gottrand F. Parenteral nutrition with fish oil supplements is safe and seems to be effective in severe preterm neonates with respiratory distress syndrome. Acta Paediatr. 2015;104:e534–6. https://doi.org/10.1111/apa.13091

    Article  PubMed  Google Scholar 

  26. Zhan L, Yang I, Kong B, Shen J, Gorczyca L, Memon N. et al. Dysregulation of bile acid homeostasis in parenteral nutrition mouse model. Am J Physiol Gastrointest liver Physiol. 2016;310:G93–G102. https://doi.org/10.1152/ajpgi.00252.2015

    Article  PubMed  Google Scholar 

  27. Bae JS, Park JM, Lee J, Oh BC, Jang SH, Lee YB. et al. Amelioration of non-alcoholic fatty liver disease with NPC1L1-targeted IgY or n-3 polyunsaturated fatty acids in mice. Metab Clin Exp. 2017;66:32–44. https://doi.org/10.1016/j.metabol.2016.10.002

    Article  CAS  PubMed  Google Scholar 

  28. Buchman AL, Iyer K, Fryer J. Parenteral nutrition-associated liver disease and the role for isolated intestine and intestine/liver transplantation. Hepatol (Baltim, MD). 2006;43:9–19. https://doi.org/10.1002/hep.20997

    Article  Google Scholar 

  29. Turner JM, Josephson J, Field CJ, Wizzard PR, Ball RO, Pencharz PB. et al. Liver disease, systemic inflammation, and growth using a mixed parenteral lipid emulsion, containing soybean oil, fish oil, and medium chain triglycerides, compared with soybean oil in parenteral nutrition-fed neonatal piglets. JPEN J Parenter Enter Nutr. 2016;40:973–81. https://doi.org/10.1177/0148607115579711

    Article  CAS  Google Scholar 

  30. Fell GL, Cho BS, Pan A, Nose V, Anez-Bustillos L, Dao DT. et al. A comparison of fish oil sources for parenteral lipid emulsions in a murine model. JPEN J Parenter Enter Nutr. 2017;41:181–7. https://doi.org/10.1177/0148607116640275

    Article  CAS  Google Scholar 

  31. Zhu X, Xiao Z, Xu Y, Zhao X, Cheng P, Cui N. et al. Differential impacts of soybean and fish oils on hepatocyte lipid droplet accumulation and endoplasmic reticulum stress in primary rabbit hepatocytes. Gastroenterol Res Pract. 2016;2016:9717014. https://doi.org/10.1155/2016/9717014

    Article  PubMed  PubMed Central  Google Scholar 

  32. Calkins KL, DeBarber A, Steiner RD, Flores MJ, Grogan TR, Henning SM, et al. Intravenous fish oil and pediatric intestinal failure-associated liver disease: changes in plasma phytosterols, cytokines, and bile acids and erythrocyte fatty acids. JPEN J Parenter Enteral Nutr 2017:148607117709196. https://doi.org/10.1177/0148607117709196

  33. Glenn JO, Wischmeyer PE. Enteral fish oil in critical illness: perspectives and systematic review. Curr Opin Clin Nutr Metab Care. 2014;17:116–23. https://doi.org/10.1097/mco.0000000000000039

    Article  PubMed  Google Scholar 

  34. Skouroliakou M, Konstantinou D, Koutri K, Kakavelaki C, Stathopoulou M, Antoniadi 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;64:940–7. https://doi.org/10.1038/ejcn.2010.98

    Article  CAS  PubMed  Google Scholar 

  35. Arezzini B, Vecchio D, Signorini C, Stringa B, Gardi C. F2-isoprostanes can mediate bleomycin-induced lung fibrosis. Free Radic Biol Med. 2017;115:1–9.

    Article  Google Scholar 

  36. Kambia N, Dine T, Gressier B, Frimat B, Cazin J, Luyckx M, et al. Correlation between exposure to phthalates and concentrations of malondialdehyde in infants and children undergoing cyclic parenteral nutrition. JPEN J Parenter Enter Nutr. 2011;35:395–401.

    Article  CAS  Google Scholar 

  37. Qi X, Qin Z, Tang J, Han P, Xing Q, Wang K, et al. Omega-3 polyunsaturated fatty acids ameliorates testicular ischemia-reperfusion injury through the induction of Nrf2 and inhibition of NF-κB in rats. Exp Mol Pathol. 2017;103:44–50.

    Article  CAS  Google Scholar 

  38. Barden A, Burke V, Mas E, Beilin L, Puddey I, Watts G, et al. n-3 fatty acids reduce plasma 20-hydroxyeicosatetraenoic acid and blood pressure in patients with chronic kidney disease. J Hypertens. 2015;33:1947–53.

    Article  CAS  Google Scholar 

  39. Deshpande G, Simmer K, Deshmukh M, Mori TA, Croft KD, Kristensen J. Fish oil (SMOFlipid) and olive oil lipid (clinoleic) in very preterm neonates. J Pediatr Gastroenterol Nutr. 2014;58:179–84. https://doi.org/10.1097/mpg.0000000000000174

    Article  CAS  Google Scholar 

  40. See VHL, Mas E, Prescott SL, Beilin LJ, Burrows S, Barden AE. et al. Effects of postnatal omega-3 fatty acid supplementation on offspring pro-resolving mediators of inflammation at 6 months and 5 years of age: a double blind, randomized controlled clinical trial. Prostaglandins Leukot Essent Fat Acids. 2017;126:126–32. https://doi.org/10.1016/j.plefa.2017.08.008

    Article  CAS  Google Scholar 

  41. Jalabert A, Grand A, Steghens J-P, Barbotte E, Pigue C, Picaud J-C. Lipid peroxidation in all-in-one admixtures for preterm neonates: impact of amount of lipid, type of lipid emulsion and delivery condition. Acta Paediatr. 2011;100:1200–5. https://doi.org/10.1111/j.1651-2227.2011.02269.x

    Article  CAS  PubMed  Google Scholar 

  42. Wang Y, Feng Y, Lu L-N, Wang W-P, He Z-J, Xie L-J. et al. The effects of different lipid emulsions on the lipid profile, fatty acid composition, and antioxidant capacity of preterm infants: a double-blind, randomized clinical trial. Clin Nutr. 2016;35:1023–31. https://doi.org/10.1016/j.clnu.2015.10.011

    Article  CAS  PubMed  Google Scholar 

  43. Anez-Bustillos L, Dao DT, Fell GL, Baker MA, Gura KM, Bistrian BR et al. Redefining essential fatty acids in the era of novel intravenous lipid emulsions. Clin Nutr 2017:S0261-5614. https://doi.org/10.1016/j.clnu.2017.07.004

    Article  CAS  Google Scholar 

  44. de Meijer VE, Le HD, Meisel JA, Gura KM, Puder M. Parenteral fish oil as monotherapy prevents essential fatty acid deficiency in parenteral nutrition-dependent patients. J Pediatr Gastroenterol Nutr. 2010;50:212–8. https://doi.org/10.1097/MPG.0b013e3181bbf51e

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Riedy M, DePaula B, Puder M, Gura KM, Sztam KA. Higher doses of fish oil-based lipid emulsions used to treat inadequate weight gain and rising triene:tetraene ratio in a severely malnourished infant with intestinal failure-associated liver disease. J Parenter Enter Nutr. 2016;41:667–71. https://doi.org/10.1177/0148607116661031

    Article  CAS  Google Scholar 

  46. Wang L, Zhang J, Gao J, Qian Y, Ling Y. The effect of fish oil-based lipid emulsion and soybean oil-based lipid emulsion on cholestasis associated with long-term parenteral nutrition in premature infants. Gastroenterol Res Pract. 2016;2016:4139164. https://doi.org/10.1155/2016/4139164

    Article  PubMed  PubMed Central  Google Scholar 

  47. Nandivada P, Baker MA, Mitchell PD, O’Loughlin AA, Potemkin AK, Anez-Bustillos L, et al. Predictors of failure of fish-oil therapy for intestinal failure-associated liver disease in children. Am J Clin Nutr. 2016;104:663–70. https://doi.org/10.3945/ajcn.116.137083

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Belza C, Thompson R, Somers GR, de Silva N, Fitzgerald K, Steinberg K, et al. Persistence of hepatic fibrosis in pediatric intestinal failure patients treated with intravenous fish oil lipid emulsion. J Pediatr Surg. 2017;52:795–801. https://doi.org/10.1016/j.jpedsurg.2017.01.048

    Article  PubMed  Google Scholar 

  49. Manzanares W, Langlois PL. [Fish oil containing lipid emulsions in critically ill patients: critical analysis and future perspectives]. Med Intensiv. 2016;40:39–45. https://doi.org/10.1016/j.medin.2015.07.006

    Article  CAS  Google Scholar 

  50. Nanji AA, Anderson FH. Sensitivity and specificity of liver function tests in the detection of parenteral nutrition-associated cholestasis. JPEN J Parenter Enter Nutr. 1985;9:307–8. https://doi.org/10.1177/0148607185009003307

    Article  CAS  Google Scholar 

  51. Batra A, Keys S, Johnson M, Wheeler R, Beattie R. Epidemiology, management and outcome of ultrashort bowel syndrome in infancy. Arch Dis Child Fetal Neonatal Ed. 2017;102:F551–6.

    Article  Google Scholar 

  52. Abad-Lacruz A, González-Huix F, Esteve M, Fernández-Bañares F, Cabré E, Boix J, et al. Liver function tests abnormalities in patients with inflammatory bowel disease receiving artificial nutrition: a prospective randomized study of total enteral nutrition vs total parenteral nutrition. JPEN J Parenter Enter Nutr. 1990;14:618–21.

    Article  CAS  Google Scholar 

  53. Mehta N, Skillman H, Irving S, Coss-Bu J, Vermilyea S, Farrington E, et al. Guidelines for the provision and assessment of nutrition support therapy in the pediatric critically ill patient: Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition. JPEN J Parenter Enter Nutr. 2017;41:706–42.

    Article  Google Scholar 

  54. Vafa H, Ballarin A, Arvanitakis M, Vereecken S, Dutat F, Lagasse C, et al. Lessons from a 20 year experience of home parenteral nutrition in adult patients. Acta Gastroenterol Belg. 2010;73:451–6.

    CAS  PubMed  Google Scholar 

  55. Lam HS, Tam YH, Poon TC, Cheung HM, Yu X, Chan BP, 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;105:290–6. https://doi.org/10.1159/000358267

    Article  CAS  PubMed  Google Scholar 

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Funding

Funding

This work was supported by the Shanghai Pujiang Program [grant number 17PJD026]; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition (14DZ2272400); Shanghai Municipal Commission of Health and Family Planning (2013ZYJB0017); Science and Technology Commission of Shanghai Municipality (14411950400/14411950401); and the National Natural Science Foundation of China-Key Program (81630039).

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  1. Tian Zhang and Nan Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatric Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Tian Zhang & Wei Cai

  2. Shanghai Institute of Pediatric Research, Shanghai, China

    Tian Zhang, Nan Wang, Weihui Yan, Lina Lu, Yijing Tao, Ying Wang & Wei Cai

  3. Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China

    Tian Zhang, Nan Wang, Weihui Yan, Lina Lu, Yijing Tao, Ying Wang & Wei Cai

  4. Department of Clinical Nutrition, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Nan Wang, Weihui Yan, Lina Lu, Yijing Tao & Ying Wang

  5. Department of Pharmacy, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Fang Li

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Correspondence to Ying Wang or Wei Cai.

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Zhang, T., Wang, N., Yan, W. et al. Effect of a fish oil-based lipid emulsion on intestinal failure-associated liver disease in children. Eur J Clin Nutr 72, 1364–1372 (2018). https://doi.org/10.1038/s41430-018-0096-z

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