Kara Calkins¹, Stephen Shew², James Dunn², Douglas Farmer², Robert Venick^1,2

¹Department of Pediatrics, UCLA , Los Angeles, CA, United States; ²Department of Surgery, UCLA, Los Angeles, CA, United States

Background: Intestinal Failure Associated Liver Disease (IFALD) is a major cause of mortality among children with intestinal failure (IF). Cohort studies have reported that IV fish oil (FO) reverses cholestasis and prevents death and transplant.

Objective: To determine the efficacy of a finite FO course.

Methods: FDA and IRB approval was obtained. Inclusion criteria: direct bilirubin (DB) ≥ 2 mg/dL, > 2 weeks of age < 18 years, acquired/congenital GI disorder, and > 60% of parenteral nutrition (PN) calories. IV soybean oil (SO) was replaced with FO (Omegaven™), 1 gm/kg/d IV for 24 weeks or until death or transplant. For comparison, historical SO controls who fulfilled inclusion criteria were matched one-to-one. Baseline characteristics were compared using Chi-square and t-tests. Liver function tests and safety markers were compared over time using repeated measures of ANOVA.

Results: 8 FO subjects (median enrollment age: 68 days) were compared to 8 SO. There were no significant differences in baseline demographics, GI diagnosis/anatomy, PN calories, glucose and protein, transaminases, alkaline phosphatase, platelet count, triglycerides and albumin. At enrollment FO had more septic episodes (1.6±0.9 vs 0.4±0.7, p<0.05), higher DB (6.5±3.4 vs 3.7±1.7 mg/dL, p<0.05), received more enteral calories (23±13 vs 3±4%, p<0.005) and less SO (1.3±0.8 vs 2.7±0.5 g/kg/day, p<0.005). At the study endpoint, significant improvements were observed for FO vs SO in DB (0.2±0.1 vs 11.2±5.8 mg/dL, p<0.01), AST (90±47 vs 268±130 U/L, p<0.05) and platelet count (265±166 vs 108±71, p<0.05); no differences were seen in ALT, alkaline phosphatase, albumin, or transplant-free survival. Median time to reversal of cholestasis (DB < 2 mg/dL) in FO was 14±3.2 weeks. No adverse events were observed.

Conclusions: This unique prospective, case-control study demonstrates that short-term administration of FO reverses cholestasis. Follow-up is required to corroborate the long-term sustainability of this effect. This study supports the existing clinical practice that enteral nutrition and low dose IV fat appear to ameliorate IFALD.