Fish oil intravenous lipid emulsion (FOLE) monotherapy was found to be a safe and well-tolerated parenteral lipid for children with intestinal failure-associated liver disease (IFALD), defined as a serum direct bilirubin (DB) concentration of 2 or more mg/dL, and should be considered the preferred intravenous liquid emulsion source when DB reaches 2 mg/dL in children who require lipids, according to an integrated analysis published in The Journal of Pediatrics.
FOLE therapy was found to improve disease progression when initiated as soon as DB hit 2 mg/dL. The treatment also correlated with a higher rate of cholestasis resolution, lower aminotransferase with platelet ratio index (APRI) scores, and fewer liver transplants in the 189 children who received FOLE compared with the 73 historical controls who were treated with soybean oil intravenous lipid emulsion (SOLE).
Specifically, 65% of FOLE recipients experienced cholestasis resolution vs 16% of SOLE recipients (P <.0001). APRI scores improved with FOLE (1.235 vs 0.810 and 0.758, P <.02) but worsened with SOLE (0.540 vs 2.564 and 2.098, P ≤.0003) when baseline scores were compared with cholestasis resolution and end of study, respectively. FOLE led to greater reductions in liver transplantation than SOLE (4% vs 12%, P =.0245), and the probability of liver transplantation in relation to baseline DB was lower in FOLE vs SOLE recipients (1% vs 9% at DB of 2 mg/dL and 8% vs 35% at DB of 12.87 mg/dL; P =.0022 for both). Death rates were similar with FOLE and SOLE at DB of 2 mg/dL and 12.87 mg/dL (10% vs 14% and 17% vs 23%, respectively; P =.36 for both).
Prolonged use of parenteral nutrition can cause IFALD, and unless it is discontinued, cholestasis can progress from fibrosis to cirrhosis and, ultimately, death from end-stage liver disease. SOLE has been linked with IFALD; as a result, FOLE was introduced in the United States in 2004 for compassionate use in patients with IFALD.
Regarding study limitations, the investigators stated that a randomized controlled trial “would have been preferable” but cited “ethical considerations, lack of equipoise, and recruitment challenges” as hindrances to its execution. “Additional limitations include a relatively small sample size and changes in surgical, medical, and nutritional practice between the 2 eras that could not be controlled for in this study,” they concluded.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
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. Published online September 30, 2020. doi:10.1016/j.jpeds.2020.09.068