Compassionate Use of an Intravenous Fish Oil Emulsion in the Treatment of Liver Injury in Infants

Summary

To provide a mechanism for critically ill infants with parenteral nutrition (PN) associated cholestasis to receive Omegaven for compassionate use situations for which there are no satisfactory alternative treatments.

Timeline

Start

2008-09

Primary completion

2019-03-27

Completion

2020-03-27

Publications

• Background Dudrick SJ, Wilmore DW, Vars HM, Rhoads JE. Long-term total parenteral nutrition with growth, development, and positive nitrogen balance. Surgery. 1968 Jul;64(1):134-42. No abstract available.
• Background Wilmore DW, Dudrick SJ. Growth and development of an infant receiving all nutrients exclusively by vein. JAMA. 1968 Mar 4;203(10):860-4. No abstract available.
• Background Mullick FG, Moran CA, Ishak KG. Total parenteral nutrition: a histopathologic analysis of the liver changes in 20 children. Mod Pathol. 1994 Feb;7(2):190-4.
• Background Freund HR. Abnormalities of liver function and hepatic damage associated with total parenteral nutrition. Nutrition. 1991 Jan-Feb;7(1):1-5; discussion 5-6.
• Background Beath SV, Davies P, Papadopoulou A, Khan AR, Buick RG, Corkery JJ, Gornall P, Booth IW. Parenteral nutrition-related cholestasis in postsurgical neonates: multivariate analysis of risk factors. J Pediatr Surg. 1996 Apr;31(4):604-6. doi: 10.1016/s0022-3468(96)90507-2.
• Background Greenberg GR, Wolman SL, Christofides ND, Bloom SR, Jeejeebhoy KN. Effect of total parenteral nutrition on gut hormone release in humans. Gastroenterology. 1981 May;80(5 pt 1):988-93. No abstract available.
• Background Yeh SL, Chen WJ, Huang PC. Effects of L-glutamine on induced hepatosteatosis in rats receiving total parenteral nutrition. J Formos Med Assoc. 1995 Oct;94(10):593-9.
• Background Kubota A, Yonekura T, Hoki M, Oyanagi H, Kawahara H, Yagi M, Imura K, Iiboshi Y, Wasa K, Kamata S, Okada A. Total parenteral nutrition-associated intrahepatic cholestasis in infants: 25 years' experience. J Pediatr Surg. 2000 Jul;35(7):1049-51. doi: 10.1053/jpsu.2000.7769.
• Background Moss RL, Das JB, Ansari G, Raffensperger JG. Hepatobiliary dysfunction during total parenteral nutrition is caused by infusate, not the route of administration. J Pediatr Surg. 1993 Mar;28(3):391-6; discussion 396-7. doi: 10.1016/0022-3468(93)90238-g.
• Background Helms RA, Christensen ML, Mauer EC, Storm MC. Comparison of a pediatric versus standard amino acid formulation in preterm neonates requiring parenteral nutrition. J Pediatr. 1987 Mar;110(3):466-70. doi: 10.1016/s0022-3476(87)80519-x. No abstract available.
• Background Moss RL, Haynes AL, Pastuszyn A, Glew RH. Methionine infusion reproduces liver injury of parenteral nutrition cholestasis. Pediatr Res. 1999 May;45(5 Pt 1):664-8. doi: 10.1203/00006450-199905010-00009.
• Background Meehan JJ, Georgeson KE. Prevention of liver failure in parenteral nutrition-dependent children with short bowel syndrome. J Pediatr Surg. 1997 Mar;32(3):473-5. doi: 10.1016/s0022-3468(97)90609-6.
• Background Whalen GF, Shamberger RC, Perez-Atayde A, Folkman J. A proposed cause for the hepatic dysfunction associated with parenteral nutrition. J Pediatr Surg. 1990 Jun;25(6):622-6. doi: 10.1016/0022-3468(90)90348-d.
• Background Zamir O, Nussbaum MS, Bhadra S, Subbiah MT, Rafferty JF, Fischer JE. Effect of enteral feeding on hepatic steatosis induced by total parenteral nutrition. JPEN J Parenter Enteral Nutr. 1994 Jan-Feb;18(1):20-5. doi: 10.1177/014860719401800120.
• Background Kaminski DL, Adams A, Jellinek M. The effect of hyperalimentation on hepatic lipid content and lipogenic enzyme activity in rats and man. Surgery. 1980 Jul;88(1):93-100. No abstract available.
• Background Hultin M, Carneheim C, Rosenqvist K, Olivecrona T. Intravenous lipid emulsions: removal mechanisms as compared to chylomicrons. J Lipid Res. 1995 Oct;36(10):2174-84.
• Background Qi K, Al-Haideri M, Seo T, Carpentier YA, Deckelbaum RJ. Effects of particle size on blood clearance and tissue uptake of lipid emulsions with different triglyceride compositions. JPEN J Parenter Enteral Nutr. 2003 Jan-Feb;27(1):58-64. doi: 10.1177/014860710302700158.
• Background Nestel PJ. Effects of N-3 fatty acids on lipid metabolism. Annu Rev Nutr. 1990;10:149-67. doi: 10.1146/annurev.nu.10.070190.001053. No abstract available.
• Background Chen WJ, Yeh SL, Huang PC. Effects of fat emulsions with different fatty acid composition on plasma and hepatic lipids in rats receiving total parenteral nutrition. Clin Nutr. 1996 Feb;15(1):24-8. doi: 10.1016/s0261-5614(96)80257-3.
• Background Yeh SL, Chen WJ, Huang PC. Effects of fish oil and safflower oil emulsions on diet-induced hepatic steatosis in rats receiving total parenteral nutrition. Clin Nutr. 1996 Apr;15(2):80-3. doi: 10.1016/s0261-5614(96)80024-0.
• Background Kinsella JE, Lokesh B, Broughton S, Whelan J. Dietary polyunsaturated fatty acids and eicosanoids: potential effects on the modulation of inflammatory and immune cells: an overview. Nutrition. 1990 Jan-Feb;6(1):24-44; discussion 59-62. No abstract available.
• Background Gura KM, Lee S, Valim C, Zhou J, Kim S, Modi BP, Arsenault DA, Strijbosch RA, Lopes S, Duggan C, Puder M. Safety and efficacy of a fish-oil-based fat emulsion in the treatment of parenteral nutrition-associated liver disease. Pediatrics. 2008 Mar;121(3):e678-86. doi: 10.1542/peds.2007-2248.
• Background Strijbosch RA, Lee S, Arsenault DA, Andersson C, Gura KM, Bistrian BR, Puder M. Fish oil prevents essential fatty acid deficiency and enhances growth: clinical and biochemical implications. Metabolism. 2008 May;57(5):698-707. doi: 10.1016/j.metabol.2008.01.008.
• Gura KM, Calkins KL, Premkumar MH, Puder M. Use of Intravenous Soybean and Fish Oil Emulsions in Pediatric Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Analysis Report on Extrahepatic Adverse Events. J Pediatr. 2022 Feb;241:173-180.e1. doi: 10.1016/j.jpeds.2021.10.030. Epub 2021 Oct 23.
• Gura KM, Premkumar MH, Calkins KL, Puder M. Fish Oil Emulsion Reduces Liver Injury and Liver Transplantation in Children with Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Study. J Pediatr. 2021 Mar;230:46-54.e2. doi: 10.1016/j.jpeds.2020.09.068. Epub 2020 Oct 8.
• Gura K, Premkumar MH, Calkins KL, Puder M. Intravenous Fish Oil Monotherapy as a Source of Calories and Fatty Acids Promotes Age-Appropriate Growth in Pediatric Patients with Intestinal Failure-Associated Liver Disease. J Pediatr. 2020 Apr;219:98-105.e4. doi: 10.1016/j.jpeds.2019.12.065. Epub 2020 Feb 12.
• Premkumar MH, Carter BA, Hawthorne KM, King K, Abrams SA. High rates of resolution of cholestasis in parenteral nutrition-associated liver disease with fish oil-based lipid emulsion monotherapy. J Pediatr. 2013 Apr;162(4):793-798.e1. doi: 10.1016/j.jpeds.2012.10.019. Epub 2012 Nov 16.

Drugs

Indications