Conversion from SMOFlipid? to Omegaven? as a Salvage Therapy for Severe Intestinal Failure Associated Liver Disease

Introduction: Parenteral nutrition (PN) is a life-saving therapy. One of the most feared complications of intestinal failure and PN is the development of intestinal failure associated liver disease (IFALD). Modern lipid strategies with the use of a mixed lipid emulsion decreased the incidence of IFALD, but some patients still develop liver dysfunction. Omegaven® is an effective treatment of IFALD in patients receiving intralipid®, but little is known about the role of Omegaven® for the treatment of IFALD in patients treated with SMOFlipid®. The aim of this study is to review the role of Omegaven® as a salvage therapy in patients receiving SMOFlipid® that developed progressive IFALD. Methods: Retrospective study of patients managed by the intestinal failure program at The Hospital for the Sick Children from 2015 to 2022. The study cohort included children that developed advanced IFALD with the use of SMOFlipid® and converted to Omegaven for at least 7 weeks. Advanced IFALD was defined as conjugated bilirubin persistently over 50 µmol/L (2.9mg/d) and no near future possibility of PN weaning. The primary outcome was conjugated bilirubin <34 mmol/l at 6 months after initiation of Omegaven®. Descriptive statistics were used. Results: From 2015 to 2022 eight patients developed progressive IFALD while receiving SMOFlipid® and were treated with Omegaven®. Mean conjugated bilirubin at time of Omegaven initiation was 114 mmol/l (range 42-183). We excluded 2 patients from the analysis; one due to short period of treatment (4 weeks until a liver-intestine transplantation) and the other for multi-system disease that may impact the liver (chronic granulomatous disease). Following conversion to Omegaven®, 3 patients (50%) achieved improvement in bilirubin levels (Figure 1). The length of time to achieve conjugated bilirubin below 34 µmol/L (2 mg/dL) was a mean of 18.6 weeks (range 11-25; SD 7.09). In the non-responders (N=3), one patient died and 2 underwent multi-visceral transplantation. Unlike the responders, non-responders had signs of more severe IFALD prior to treatment initiation. These include: previous use of Omegaven® for advanced IFALD while on Intralipid® (n= 2); gastrointestinal bleeding secondary to portal hypertension (n= 2); need for continuous glucose infusion to prevent hypoglycemia (n= 2); and higher range of INR (1.4-2.7 in non responders vs. 1.1 - 1.2 in responders). Conclusions: Omegaven® reversed progressive IFALD in 3 out of 6 patients (50%) who received SMOFlipid® as their PN lipid source. Treatment failure was common in children with more severe IFALD prior to Omegaven® initiation, and history of previous use of Omegaven® for IFALD reversal. Larger cohorts are required to confirm the findings of this case series.