Intravenous Fish Oil and Pediatric Intestinal Failure–Associated Liver Disease: Changes in Plasma Phytosterols, Cytokines, and Bile Acids and Erythrocyte Fatty Acids

Abstract

Background Soybean oil emulsions (SO) are associated with intestinal failure–associated liver disease (IFALD); fish oil emulsions (FO) are used to treat IFALD. SO and FO differ with respect to their fatty acid and phytosterol content. In children with IFALD whose SO was replaced with FO, we aimed to (1) quantify changes in erythrocyte fatty acids and plasma phytosterols, cytokines, and bile acids and (2) correlate these changes with direct bilirubin (DB). Design This study enrolled IFALD children who received 6 months of FO. Blood samples were collected prior to FO, and after 2 weeks and 3 and 6 months of FO. The primary outcome was 3-month vs baseline biomarker concentrations Results At study initiation, the median patient age was 3 months (interquartile range [IQR], 3–17 months), and mean ± standard deviation DB was 5.6 ± 0.7 mg/dL (n = 14). Cholestasis reversed in 79% of subjects. Eicosapentaenoic and docosahexaenoic acid was greater than baseline (P < .001, all time points). Linoleic and arachidonic acid and sitosterol and stigmasterol were less than baseline (P < .05, all time points). Three- and 6-month interleukin-8 (IL-8) and total and conjugated bile acids were less than baseline (P < .05). Baseline IL-8 was correlated with baseline DB (r = 0.71, P < .01). Early changes in stigmasterol and IL-8 were correlated with later DB changes (r = 0.68 and 0.75, P < .05). Conclusion Specific fat emulsion components may play a role in IFALD. Stigmasterol and IL-8 may predict FO treatment response.

Intravenous Fish Oil and Serum Fatty Acid Profiles in Pediatric Patients With Intestinal Failure–Associated Liver Disease

“…[1][2][3] Contrary to this hypothesis, in our previous study, ARA was inversely correlated with conjugated bilirubin. 4 It remains to be determined if this is a type I error or if it is clinically relevant. In a previous study of children with non-IFALD cholestasis, ARA and DHA concentrations were inversely correlated with liver function tests.…”

Summary of Proceedings and Expert Consensus Statements From the International Summit “Lipids in Parenteral Nutrition”

“…In PN‐dependent children with existing IFALD, cholestasis can be reversed by using fish‐oil containing lipid emulsions along with management of other risk factors, especially catheter‐related infections and small‐intestinal bacterial overgrowth …”

“…In PN-dependent children with existing IFALD, cholestasis can be reversed by using fish-oil containing lipid emulsions along with management of other risk factors, especially catheter-related infections and small-intestinal bacterial overgrowth. [84][85][86][87][88][89][90][91][92][93][94][95][96] Pure fish-oil lipid emulsions have been shown to be a valuable short-term rescue treatment in cholestatic pediatric patients who require PN but should not be used as the sole source of lipids over a long period. 2 Based on evidence from clinical studies, administration of a composite lipid emulsion containing fish oil should be considered as first-line treatment for infants and children with existing cholestasis.…”

Lipid Emulsion Use in Pediatric Patients Requiring Long‐Term Parenteral Nutrition

“…There have been efforts to prevent or reverse cholestasis by modifying lipid administration in patients requiring long‐term PN. Modifications include lipid minimization, temporarily discontinuing lipids, and using lipid emulsions containing lipid sources other than soybean oil (eg, pure fish oil or composite lipid emulsions with or without fish oil) …”

“…Modifications include lipid minimization, [70][71][72] temporarily discontinuing lipids, 52 and using lipid emulsions containing lipid sources other than soybean oil (eg, pure fish oil or composite lipid emulsions with or without fish oil). [73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88]…”