Parenteral Fish Oil Improves Outcomes in Patients With Parenteral Nutrition-Associated Liver Injury

Department of Surgery, Children's Hospital Boston and Harvard Medical School, Boston, MA, USA.
Annals of surgery (Impact Factor: 8.33). 08/2009; 250(3):395-402. DOI: 10.1097/SLA.0b013e3181b36657
Source: PubMed


The objective was to determine the safety and efficacy of a fish oil-based intravenous lipid emulsion (ILE) in the treatment of parenteral nutrition-associated liver disease (PNALD).
PNALD can be a lethal complication in children with short bowel syndrome (SBS). ILE based on soybean oil administered with parenteral nutrition (PN) may contribute to its etiology.
We performed an open-labeled trial of a fish oil-based ILE in 42 infants with SBS who developed cholestasis (serum direct bilirubin >2 mg/dL) while receiving soybean oil-based ILE. Safety and efficacy outcomes were compared with those from a contemporary cohort of 49 infants with SBS and cholestasis whose PN course included soybean ILE only. The primary efficacy end-point was time to reversal of cholestasis (direct bilirubin <=2 mg/dL).
Three deaths and 1 liver transplantation occurred in the fish oil cohort, compared with 12 deaths and 6 transplants in the soybean oil cohort (P = 0.005). Among survivors not transplanted during PN, cholestasis reversed while receiving PN in 19 of 38 patients in the fish oil cohort versus 2 of 36 patients in the soybean oil cohort. Based on Cox models, subjects receiving fish oil-based ILE experienced reversal of cholestasis 6 times faster (95% CI: 2.0-37.3) than those receiving soybean oil-based ILE. The provision of fish oil-based ILE was not associated with hypertriglyceridemia, coagulopathy, or essential fatty acid deficiency. Moreover, hypertriglyceridemic events and abnormal international normalized ratio levels were more common among controls.
Fish oil-based ILE is safe, may be effective in treating PNALD, and may reduce mortality and organ transplantation rates in children with SBS.

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    • "Clinically, the administration of FO-based lipid emulsions has shown promise in the prevention and reversal of PNALD. Puder and colleagues have reported that infants on FO reversed cholestasis six times faster than infants on SO. [5] The molecular mechanisms underlying the clinical benefit observed with FO are unclear. The etiology of hepatobiliary dysfunction and systemic inflammation is likely multifactorial, with the relative effects of enteral versus parenteral feeding, high-carbohydrate and high-glucose nutrition, and the composition of intravenous lipid being poorly understood. "
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    ABSTRACT: Parenteral nutrition (PN), including intravenous lipid administration, is a life-saving therapy but can be complicated by cholestasis and liver disease. The administration of intravenous soy bean oil (SO) has been associated with the development of liver disease, while the administration of intravenous fish oil (FO) has been associated with the resolution of liver disease. The biochemical mechanism of this differential effect is unclear. This study compares SO and FO lipid emulsions in a murine model of hepatic steatosis, one of the first hits in PN-associated liver disease. We established a murine model of hepatic steatosis in which liver injury is induced by orally feeding mice a PN solution. C57BL/6J mice were randomized to receive PN alone (a high carbohydrate diet (HCD)), PN plus intravenous FO (Omegaven®; Fresenius Kabi AG, Bad Homburg VDH, Germany), PN plus intravenous SO (Intralipid®; Fresenius Kabi AG, Bad Homburg v.d.H., Germany, for Baxter Healthcare, Deerfield, IL), or a chow diet. After 19 days, liver tissue was harvested from all animals and subjected to metabolomic profiling. The administration of an oral HCD without lipid induced profound hepatic steatosis. SO was associated with macro- and microvesicular hepatic steatosis, while FO largely prevented the development of steatosis. 321 detectable compounds were identified in the metabolomic analysis. HCD induced de novo fatty acid synthesis and oxidative stress. Both FO and SO relieved some of the metabolic shift towards de novo lipogenesis, but FO offered additional advantages in terms of lipid peroxidation and the generation of inflammatory precursors. Improved lipid metabolism combined with reduced oxidative stress may explain the protective effect offered by intravenous FO in vivo.
    Full-text · Article · Apr 2013 · PLoS ONE
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    • "Reference Type Findings Class [86] Case series 4 patients with " ultra " short bowel IV FOBLE (1 g kg −1 d −1 ) reversed or prevented PNAC in 4/4 [87] Case series 4 patients with PNALD, PN dependence, short bowel IV FOBLE (1 g kg −1 d −1 ) reversed or prevented PNAC in 3/4 [88] Case report Single patient with SBS caused by midgut volvulus IV FOBLE (1.5 g kg −1 d −1 ) reversed PNAC [89] Case series 2 patients with SBS, PN dependence, and PNALD IV FOBLE (1 g kg −1 d −1 ) reversed PNALD in 2/2 [90] Retrospective cohort study 18 patients with SBS and PNAC IV Median time to reversal of cholestasis was 9.4 wk n the FOBLE cohort compared with 44.1 wk in historical controls (soybean oil intralipid) [91] Prospective trial Open-labeled trial of a FOBLE in 42 infants with SBS with PNAC while receiving soybean oil–based ILE. Subjects receiving fish oil–based ILE experienced reversal of PNAC 6 times faster than those receiving soybean oil–based ILE. "
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    ABSTRACT: The aim of this study was to review evidence-based data addressing key clinical questions regarding parenteral nutrition-associated cholestasis (PNAC) and parenteral nutrition-associated liver disease (PNALD) in children. Data were obtained from PubMed, Medicine databases of the English literature (up to October 2010), and the Cochrane Database of Systematic Reviews. The review of PNAC/PNALD has been divided into 4 areas to simplify one's understanding of the current knowledge regarding the pathogenesis and treatment of this disease: (1) nonnutrient risk factors associated with PNAC, (2) PNAC and lipid emulsions, (3) nutritional (nonlipid) considerations in the prevention of PNAC, and (4) supplemental medications in the prevention and treatment of PNAC. The data for each topic area relevant to the clinical practice of pediatric surgery were reviewed, evaluated, graded, and summarized. Although the conditions of PNAC and PNALD have been well recognized for more than 30 years, only a few concrete associations and treatment protocols have been established.
    Full-text · Article · Jan 2012 · Journal of Pediatric Surgery
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    • "In a second study, 42 patients with short bowel syndrome who had developed cholestasis while receiving soybean oil– based lipid emulsions were treated with Omegaven. Safety and efficacy outcomes were compared with a contemporary cohort of 49 patients treated solely with soybean oil–based lipid emulsions [4]. Findings showed significantly more deaths and transplants in the cohort who received the soybean oil–based lipid emulsion in comparison with the Omegaven group. "
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    ABSTRACT: Microvillous inclusion disease is a congenital intestinal epithelial cell disorder leading to lifelong intestinal failure. In this report, we discuss the use of a fish oil-based lipid emulsion in the treatment of 3 patients with microvillous inclusion disease who developed parenteral nutrition-associated liver disease.
    Full-text · Article · Dec 2011 · Journal of Pediatric Surgery
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