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
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
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
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.
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.
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.
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.
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
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.
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.
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
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
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
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
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.
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.
Pironi L. Definitions of intestinal failure and the short bowel syndrome. Best Pract Res Clin Gastroenterol. 2016;30:173–85.
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
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
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
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
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
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.
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
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
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
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
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
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
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
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
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
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
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
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
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.
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.
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.
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.
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
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
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
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
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
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
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
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
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
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
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
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
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.
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.
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.
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.
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
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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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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DOI: https://doi.org/10.1038/s41430-018-0096-z
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