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

ABSTRACT: BACKGROUND:Intravenous fish oil (FO) treats pediatric intestinal failure-associated liver disease (IFALD). There are concerns that a lipid emulsion composed of ?-3 fatty acids will cause an essential fatty acid deficiency (EFAD). This study's objective was to quantify the risk for abnormal fatty acid concentrations in children treated with FO. METHODS:Inclusion criteria for this prospective study were children with intestinal failure. Intravenous soybean oil (SO) was replaced with FO for no longer than 6 months. Serum fatty acids were analyzed using linear and logistic models, and compared with age-based norms to determine the percentage of subjects with low and high concentrations. RESULTS:Subjects (n = 17) started receiving FO at a median of 3.6 months (interquartile range 2.4-9.6 months). Over time, ?-linolenic, linoleic, arachidonic, and Mead acid decreased, whereas docosahexaenoic and eicosapentaenoic acid increased (P < 0.001 for all). Triene-tetraene ratios remained unchanged (P = 1). Although subjects were 1.8 times more likely to develop a low linoleic acid while receiving FO vs SO (95% CI: 1.4-2.3, P < 0.01), there was not a significant risk for low arachidonic acid. Subjects were 1.6 times more likely to develop high docosahexaenoic acid while receiving FO vs SO; however, this was not significant (95% CI: 0.9-2.6, P = 0.08). CONCLUSION:In this cohort of parenteral nutrition-dependent children, switching from SO to FO led to a decrease in essential fatty acid concentrations, but an EFAD was not evident. Low and high levels of fatty acids developed. Further investigation is needed to clarify if this is clinically significant.

SUBMITTER: Ong ML

PROVIDER: S-EPMC6720103 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Project description:BackgroundThere is evidence that microRNA (MIR) 122 is a biomarker for various liver diseases in adults and children. To date, MIR122 has not been explored in children with intestinal failure-associated liver disease (IFALD, or hyperbilirubinemia associated with prolonged parenteral nutrition).ObjectivesThis study's purpose was to investigate changes in plasma miR-122, correlate miR-122 with serum liver function tests and enzymes, and investigate changes in whole blood transcripts including miR-122 targets in a group of children with IFALD who received pure intravenous fish oil (FO) as a treatment for cholestasis.MethodsThis was a prospective, observational study that enrolled children with IFALD who received intravenous FO (1 g/kg/d) and whose cholestasis resolved with FO. Plasma miR-122 was measured using reverse transcription-quantitative real-time PCR, and whole blood miR-122 targets were quantified using RNA sequencing.ResultsFourteen subjects with median age 6 mo (IQR: 3-65 mo) were enrolled. RNA sequence data were available for 4 subjects. When compared with the start of FO, median miR-122 concentrations at 6 mo of FO therapy decreased [1.0 (IQR: 1.0-1.0) compared with 0.04 (IQR: 0.01-0.6), P = 0.009]. At the start of FO, miR-122 correlated with conjugated bilirubin (r = 0.56; P = 0.038). At ∼3 mo of FO, miR-122 correlated with conjugated bilirubin (r = 0.56; P = 0.045). Reactive oxygen species, heme metabolism, coagulation, adipogenesis, IL-6-Janus kinase-signal transducer and activator of transcription (JAK-STAT) 3, IL-2-STAT5, transforming growth factor-β, TNF-α, inflammatory response, mammalian target of rapamycin gene families (normalized enrichment scores < -1.4), and miR-122 target genes were significantly downregulated with FO.ConclusionsIn this small cohort of young children with IFALD, miR-122 decreased with FO therapy and correlated with conjugated bilirubin. Key pathways involving oxidation, inflammation, cellular differentiation, and nutrient regulation were downregulated. Data from this study provide information about IFALD and FO. This trial was registered at www.clinicaltrials.gov as NCT00969332.

Project description:BackgroundParenteral fish-oil (FO) therapy is a safe and effective treatment for intestinal failure-associated liver disease (IFALD). Patients whose cholestasis does not resolve with FO may progress to end-stage liver disease.ObjectiveWe sought to identify factors associated with the failure of FO therapy in treating IFALD to guide prognostication and referral guidelines.DesignProspectively collected data for patients treated with FO at Boston Children's Hospital from 2004 to 2014 were retrospectively reviewed. Resolution of cholestasis was defined as sustained direct bilirubin (DB) <2 mg/dL, and treatment failure as liver transplantation or death while DB was >2 mg/dL as of July 2015. Demographics, laboratory values, and medical history at FO therapy initiation were compared between patients who achieved resolution of cholestasis and those who failed therapy.ResultsAmong 182 patients treated with FO, 86% achieved resolution of cholestasis and 14% failed therapy. Patients who failed therapy had median (IQR) lower birth weight [1020 g (737, 1776 g) compared with 1608 g (815, 2438 g); P = 0.03] and were older at FO initiation [20.4 wk (9.9, 38.6 wk) compared with 11.7 wk (7.3, 21.4 wk); P = 0.02] than patients whose cholestasis resolved. Patients who failed therapy had more advanced liver disease at therapy initiation than patients whose cholestasis resolved, as evidenced by lower median (IQR) γ-glutamyltransferase [54 U/L (41, 103 U/L) compared with 112 U/L (76, 168 U/L); P < 0.001], higher DB [10.4 mg/dL (7.5, 14.1 mg/dL) compared with 4.4 mg/dL (3.1, 6.6 mg/dL); P < 0.001], and a higher pediatric end-stage liver disease (PELD) score [22 (14, 25) compared with 12 (7, 15); P < 0.001]. A PELD score of ≥15, history of gastrointestinal bleeding, age at FO initiation ≥16 wk, presence of nongastrointestinal comorbidities, and mechanical ventilation at FO initiation were independent predictors of treatment failure.ConclusionsMost infants with IFALD responded to FO therapy with resolution of cholestasis, and liver transplantation was rarely required. Early FO initiation once biochemical cholestasis is detected in parenteral nutrition-dependent patients is recommended. This trial was registered at clinicaltrials.gov as NCT00910104.

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

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