title: Predictors of failure of fish-oil therapy for intestinal failure-associated liver disease in children.
abstract: Parenteral 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.
  
  
  
  We sought to identify factors associated with the failure of FO therapy in treating IFALD to guide prognostication and referral guidelines.
  
  
  
  Prospectively 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.
  
  
  
  Among 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.
  
  
  
  Most 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.
authors: Vascular Biology Program and Department of Surgery.
authors: Prathima
authors: P
authors: Nandivada
authors: Vascular Biology Program and Department of Surgery.
authors: Meredith A
authors: MA
authors: Baker
authors: Clinical Research Center, Biostatistics Core, and.
authors: Paul D
authors: PD
authors: Mitchell
authors: Vascular Biology Program and Department of Surgery.
authors: Alison A
authors: AA
authors: O'Loughlin
authors: Vascular Biology Program and Department of Surgery.
authors: Alexis K
authors: AK
authors: Potemkin
authors: Vascular Biology Program and Department of Surgery.
authors: Lorenzo
authors: L
authors: Anez-Bustillos
authors: Vascular Biology Program and Department of Surgery.
authors: Sarah J
authors: SJ
authors: Carlson
authors: Vascular Biology Program and Department of Surgery.
authors: Duy T
authors: DT
authors: Dao
authors: Vascular Biology Program and Department of Surgery.
authors: Gillian L
authors: GL
authors: Fell
authors: Department of Pharmacy, Boston Children's Hospital, Boston, MA.
authors: Kathleen M
authors: KM
authors: Gura
authors: Vascular Biology Program and Department of Surgery, mark.puder@childrens.harvard.edu.
authors: Mark
authors: M
authors: Puder
mesh_terms: D000367:Age Factors; D001663:Bilirubin / Q000097:blood; D001724:Birth Weight; D001900:Boston / Q000453:epidemiology; D002779:Cholestasis / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D015897:Comorbidity; D018450:Disease Progression; D005217:Fat Emulsions, Intravenous / Q000627:therapeutic use*; D005395:Fish Oils / Q000627:therapeutic use*; D006471:Gastrointestinal Hemorrhage / Q000453:epidemiology; D006776:Hospitals, Pediatric; D006801:Humans; D006932:Hyperbilirubinemia / Q000209:etiology / Q000517:prevention & control; D007223:Infant; D007410:Intestinal Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology / Q000628:therapy*; D007422:Intestines / Q000503:physiopathology*; D008954:Models, Biological; D015999:Multivariate Analysis; D011379:Prognosis; D012123:Pulmonary Ventilation; D012189:Retrospective Studies; D012720:Severity of Illness Index
chemical_list: D005217:Fat Emulsions, Intravenous; D005395:Fish Oils; D001663:Bilirubin
keywords: Omegaven; cholestasis; fish oil; fish oil lipid emulsion; intestinal failure; intestinal failure–associated liver disease; parenteral fish oil; parenteral nutrition; parenteral nutrition–associated liver disease