Short-term intravenous fish oil and pediatric intestinal failure associated liver disease: 3-year follow-up on liver function and nutrition

Self Cite

Background Studies have suggested that when intravenous (IV) soybean oil (SO) is replaced with fish oil (FO), direct hyperbilirubinemia is more likely to resolve. The necessary duration of FO has not been established. This study seeks to determine if 24 weeks of FO is an effective and safe therapy for intestinal failure associated liver disease (IFALD). Materials and Methods This is a clinical trial using patients with IFALD between the ages of 2 weeks and 18 years. SO was replaced with FO (1 g/kg/day) in 10 subjects who were receiving the majority of their calories from parenteral (PN). Subjects were compared to 20 historical controls receiving SO. SO for both groups was prescribed by the primary medical team at variable doses. The primary outcome was time to reversal of cholestasis. Secondary outcomes were death, transplant, and full enteral feeds. Safety measurements included growth, essential fatty acid deficiency, and laboratory markers to assess bleeding risk. Results The Kaplan-Meier method estimates that 75% in the FO group will experience resolution of cholestasis by 17 weeks vs. 6% in the SO group (p < 0.0001). When compared to the SO group, the FO group had decreased serum direct bilirubin concentrations at weeks 8 (p=0.03), 12, 16, 20 and 24 (p< 0.0001). While length Z-score at the end of the study increased in the FO group compared to baseline (p=0.03), there were no significant differences in other outcomes. Conclusions A limited duration of FO appears to be safe and effective in reversing IFALD.

Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Pediatric Intestinal Failure–Associated Liver Disease Is Reversed With 6 Months of Intravenous Fish Oil

Calkins¹,

Dunn²,

Shew³

et al. 2013

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“…During this time, other children remained cholestasis‐free and/or achieved enteral autonomy. Based on our findings and the results of other studies, we believe that extending FO beyond 6 months could help prevent cholestasis redevelopment and liver failure in some children with IF …”

Section: Discussionsupporting

confidence: 74%

“…None of these subjects succumbed to liver failure or required a transplant . Based on our data and published literature, we amended our compassionate‐use protocol so that children who remain PN‐dependent could continue FO indefinitely …”

Section: Discussionmentioning

confidence: 99%

Long‐Term Outcomes in Children With Intestinal Failure–Associated Liver Disease Treated With 6 Months of Intravenous Fish Oil Followed by Resumption of Intravenous Soybean Oil

Wang

Venick

Shew

et al. 2018

Self Cite

Background Intravenous soybean oil (SO) is a commonly used lipid emulsion for children with intestinal failure (IF); however, it is associated with IF‐associated liver disease (IFALD). Studies have demonstrated that intravenous fish oil (FO) is an effective treatment for IFALD. However, there is a lack of long‐term data on children who stop FO and resume SO. This study's objective was to investigate our institution's outcomes for children with IFALD treated with 6 months of FO and who then restarted SO. Methods Inclusion criteria for FO included children with IFALD. Parenteral nutrition (PN)‐dependent children resumed SO after FO and were prospectively followed for 4.5 years or until death, transplant, or PN discontinuation. The primary outcome was the cumulative incidence rate (CIR) for cholestasis after FO. Results Forty‐eight subjects received FO, and conjugated bilirubin decreased over time (−0.22 mg/dL/week; 95% confidence interval [CI]: −0.25, −0.19; P < .001). The CIR for cholestasis resolution after 6 months of FO was 71% (95% CI: 54%, 82%). Twenty‐seven subjects resumed SO and were followed for a median of 16 months (range 3–51 months). While the CIR for enteral autonomy after 3 years of follow‐up was 40% (95% CI: 17%, 26%), the CIR for cholestasis and transplant was 26% (95% CI: 8%, 47%) and 6% (95% CI: 0.3%, 25%), respectively. Conclusion In this study, FO effectively treated cholestasis, and SO resumption was associated with cholestasis redevelopment in nearly one‐fourth of subjects. Long‐term FO may be warranted to prevent end‐stage liver disease.

“…The emulsifier in this lipid emulsion, based on glycerol and egg yolk phospholipid, is similar to that used in soybean IVFE. A number of case reports, case series, and retrospectively controlled trials of IV fish oil have been reported in infants with or at risk for IFALD 98 – 107 . No therapeutic or prophylactic double‐blind randomized controlled trials have been completed to demonstrate the efficacy of this therapy for this indication.…”

Section: Case Examplesmentioning

confidence: 99%

Scientific, Economic, Regulatory, and Ethical Challenges of Bringing Science‐Based Pediatric Nutrition Products to the U.S. Market and Ensuring Their Availability for Patients

Merritt

Goldsmith

2014

Many nutrition products and related drugs are unavailable or not consistently available to clinicians despite a body of clinical data and experience supporting their use. Many of these can be related to drug shortages that have increased since 2009. In addition, there are potentially useful products that are not approved for a specific use or are no longer being manufactured. This review broadly examines the product availability gap from the perspectives of a clinician/former nutrition industry medical director and an economist. The process of pediatric nutrition product and related drug innovation, as well as its drivers and the steps involved in bringing a product to market, is first described. This is followed by an assessment of factors influencing product availability beyond the innovation process, including regulatory issues, manufacturing compliance, purchasing practices, and other factors related to drug and nutrition product pricing and reimbursement. Three pediatric case examples are reviewed and placed in the context of the prior review. Last, recent and future possible steps toward closing the product availability gap are discussed.