title: Use of corticosteroids after hepatoportoenterostomy for bile drainage in infants with biliary atresia: the START randomized clinical trial.
abstract: OBJECTIVE
  Biliary atresia is the most common cause of end-stage liver disease in children. Controversy exists as to whether use of steroids after hepatoportoenterostomy improves clinical outcome.
  
  
  OBJECTIVE
  To determine whether the addition of high-dose corticosteroids after hepatoportoenterostomy is superior to surgery alone in improving biliary drainage and survival with the native liver.
  
  
  METHODS
  The multicenter, double-blind Steroids in Biliary Atresia Randomized Trial (START) was conducted in 140 infants (mean age, 2.3 months) between September 2005 and February 2011 in the United States; follow-up ended in January 2013.
  
  
  METHODS
  Participants were randomized to receive intravenous methylprednisolone (4 mg/kg/d for 2 weeks) and oral prednisolone (2 mg/kg/d for 2 weeks) followed by a tapering protocol for 9 weeks (n = 70) or placebo (n = 70) initiated within 72 hours of hepatoportoenterostomy.
  
  
  METHODS
  The primary end point (powered to detect a 25% absolute treatment difference) was the percentage of participants with a serum total bilirubin level of less than 1.5 mg/dL with his/her native liver at 6 months posthepatoportoenterostomy. Secondary outcomes included survival with native liver at 24 months of age and serious adverse events.
  
  
  RESULTS
  The proportion of participants with improved bile drainage was not statistically significantly improved by steroids at 6 months posthepatoportoenterostomy (58.6% [41/70] of steroids group vs 48.6% [34/70] of placebo group; adjusted relative risk, 1.14 [95% CI, 0.83 to 1.57]; P = .43). The adjusted absolute risk difference was 8.7% (95% CI, -10.4% to 27.7%). Transplant-free survival was 58.7% in the steroids group vs 59.4% in the placebo group (adjusted hazard ratio, 1.0 [95% CI, 0.6 to 1.8]; P = .99) at 24 months of age. The percentage of participants with serious adverse events was 81.4% [57/70] of the steroids group and 80.0% [56/70] of the placebo group (P > .99); however, participants receiving steroids had an earlier time of onset of their first serious adverse event by 30 days posthepatoportoenterostomy (37.2% [95% CI, 26.9% to 50.0%] of steroids group vs 19.0% [95% CI, 11.5% to 30.4%] of placebo group; P = .008).
  
  
  CONCLUSIONS
  Among infants with biliary atresia who have undergone hepatoportoenterostomy, high-dose steroid therapy following surgery did not result in statistically significant treatment differences in bile drainage at 6 months, although a small clinical benefit could not be excluded. Steroid treatment was associated with earlier onset of serious adverse events in children with biliary atresia.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00294684.
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Bezerra
authors.affiliation: University of Michigan, Ann Arbor.
authors.forename: Cathie
authors.initials: C
authors.lastname: Spino
authors.affiliation: University of Michigan, Ann Arbor.
authors.forename: John C
authors.initials: JC
authors.lastname: Magee
authors.affiliation: Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Shneider
authors.affiliation: UCSF Benioff Children's Hospital, San Francisco, California.
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenthal
authors.affiliation: Children's Hospital Los Angeles and University of Southern California, Los Angeles.
authors.forename: Kasper S
authors.initials: KS
authors.lastname: Wang
authors.affiliation: Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Jessi
authors.initials: J
authors.lastname: Erlichman
authors.affiliation: Children's Hospital of Philadelphia, Philadelphia, Pennsylvania17Dr Haber is now with Merck Research Laboratories, Upper Gwynedd, Pennsylvania.
authors.forename: Barbara
authors.initials: B
authors.lastname: Haber
authors.affiliation: Baylor College of Medicine and Texas Children's Hospital, Houston.
authors.forename: Paula M
authors.initials: PM
authors.lastname: Hertel
authors.affiliation: Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia.
authors.forename: Saul J
authors.initials: SJ
authors.lastname: Karpen
authors.affiliation: Mount Sinai School of Medicine, New York, New York18Dr Kerkar is now with Children's Hospital Los Angeles and University of Southern California, Los Angeles.
authors.forename: Nanda
authors.initials: N
authors.lastname: Kerkar
authors.affiliation: Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Loomes
authors.affiliation: Indiana University School of Medicine and Riley Hospital for Children, Indianapolis.
authors.forename: Jean P
authors.initials: JP
authors.lastname: Molleston
authors.affiliation: Seattle Children's Hospital, Seattle, Washington.
authors.forename: Karen F
authors.initials: KF
authors.lastname: Murray
authors.affiliation: Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia.
authors.forename: Rene
authors.initials: R
authors.lastname: Romero
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Kathleen B
authors.initials: KB
authors.lastname: Schwarz
authors.affiliation: Baylor College of Medicine and Texas Children's Hospital, Houston.
authors.forename: Ross
authors.initials: R
authors.lastname: Shepherd
authors.affiliation: University of Colorado School of Medicine and Children's Hospital Colorado, Aurora.
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Suchy
authors.affiliation: Washington University School of Medicine, St Louis, Missouri.
authors.forename: Yumirle P
authors.initials: YP
authors.lastname: Turmelle
authors.affiliation: Lurie Children's Hospital of Chicago, Chicago, Illinois.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Whitington
authors.affiliation: University of Michigan, Ann Arbor.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Moore
authors.affiliation: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland.
authors.forename: Averell H
authors.initials: AH
authors.lastname: Sherker
authors.affiliation: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland.
authors.forename: Patricia R
authors.initials: PR
authors.lastname: Robuck
authors.affiliation: University of Colorado School of Medicine and Children's Hospital Colorado, Aurora.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Sokol
mesh_terms: D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D001656:Biliary Atresia / Q000188:drug therapy* / Q000601:surgery*; D001663:Bilirubin / Q000097:blood; D004311:Double-Blind Method; D004322:Drainage / Q000379:methods; D005260:Female; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000009:adverse effects; D011171:Portoenterostomy, Hepatic; D011239:Prednisolone / Q000008:administration & dosage* / Q000009:adverse effects; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D011239:Prednisolone; D001663:Bilirubin; D008775:Methylprednisolone