Objective: 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).
Summary and Background Data: 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.
Methods: 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).
Results: 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.
Conclusions: Fish oil-based ILE is safe, may be effective in treating PNALD, and may reduce mortality and organ transplantation rates in children with SBS.
Outcomes of a fish oil-based lipid emulsion in 42 infants with short bowel syndrome and cholestasis who previously received soybean emulsions were compared with a similar, contemporary cohort of 49 infants receiving soybean emulsions. Fish oil-based emulsions may provide a safe and efficacious treatment for short bowel infants with cholestasis.
From the *Department of Surgery, Children's Hospital Boston and Harvard Medical School, Boston, MA, †the Clinical Research Program, Children's Hospital Boston and Harvard Medical School, Boston, MA, ‡Division of Gastroenterology and Nutrition, Children's Hospital Boston and Harvard Medical School, Boston, MA, and §Department of Pharmacy, Children's Hospital Boston and Harvard Medical School, Boston, MA.
Supported by NIH grant DK069621–04, March of Dimes Foundation 6-FY06–332, FDA Office of Orphan Products Development FDA 1 R01 FD003460–01, FDA 1 R01 FD003436–02, the Children's Hospital Translational Research Program Grant, and The Children's Hospital Boston Surgical Foundation (to M.P.). Joshua Ryan Rappaport Fellowship (to H.L.). The funders did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
Reprints: Mark Puder, MD, PhD, 300 Longwood Avenue, Fegan 3, Boston, MA 02115. E-mail: email@example.com.