Use of Corticosteroids After Hepatoportoenterostomy for Bile Drainage in Infants With Biliary Atresia
Year: 2014
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: IMPORTANCE: 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. DESIGN, SETTING, AND PATIENTS: 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. INTERVENTIONS: 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. MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00294684.
Source: JAMA
Authors: Jorge A. Bezerra, Cathie Spino, John C. Magee, Benjamin L. Shneider, Philip Rosenthal, Kasper S. Wang, Jessi Erlichman, Barbara Haber, Paula M. Hertel, Saul J. Karpen, Nanda Kerkar, Kathleen M. Loomes, Jean P. Molleston, Karen F. Murray, Rene Romero, Kathleen B. Schwarz, Ross Shepherd, Frederick J. Suchy, Yumirle P. Turmelle, Peter F. Whitington, Jeffrey Moore, Averell H. Sherker, Patricia R. Robuck, Ronald J. Sokol
Institutions: Cincinnati Children's Hospital Medical Center, University of Michigan, Children's Hospital of Pittsburgh, University of California, San Francisco, UCSF Benioff Children's Hospital, University of Southern California, Children's Hospital of Los Angeles, Children's Hospital of Philadelphia, Merck & Co., Inc., Rahway, NJ, USA (United States), Baylor College of Medicine, Texas Children's Hospital, Emory University, Children's Healthcare of Atlanta, Icahn School of Medicine at Mount Sinai, Riley Hospital for Children, Indiana University School of Medicine, Seattle Children's Hospital, Johns Hopkins University, Children's Hospital Colorado, University of Colorado Anschutz, Washington University in St. Louis, Lurie Children's Hospital, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: GlaxoSmithKline, University of Southern California, Children's Hospital of Philadelphia, Children's Hospital Los Angeles, Mead Johnson Nutrition, Emory University, Texas Children's Hospital, Cincinnati Children's Hospital Medical Center, Children's Hospital Colorado, Johns Hopkins University, Seattle Children's Research Institute, Children's Healthcare of Atlanta, National Institutes of Health, University of California, San Francisco, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences, Children's Hospital of Pittsburgh, University of Colorado School of Medicine, Anschutz Medical Campus
Awards: G1060344954, G1123252878, G1132462160, G113948276, G1218820423, G1260873166, G1389856746, G1533833983, G158406253, G166906552, G1674428531, G1691138911, Colorado Clinical and Translational Science Institute (UL1), G215709867, G2202404319, The Johns Hopkins Pediatric Liver Center ChiLDREN Grant, G2301731460, G2336626054, G2519346538, Indiana Clinical and Translational Sciences Institute, G2687650086, Limited Competition for the Continuation of the Childhood Liver Disease Research Network (ChilLDRen) Clinical Centers., Development of the Novel Antifungal VT-1129 for Cryptococcal Meningitis, G3028514515, G3071962596, Southern California Clinical and Translational Science Institute, G3287423920, G360827231, G3685060599, Institute of Translational Health Sciences, G3707281345, G3994857930, G4029214660, G413565259, G4205096527, G4368610743, G4577548039, G483408255, G491532010, G4934301733, G5021504846, G5058187573, G5586959461, G571758621, G586810356, Emory Clinical Center: Childhood Liver Disease Research and Education Network, G611383016, Institute for Clinical and Translational Research, G661928818, G6990385686, Understanding Cholestatic Disorders in a Collaborative Network: The Role of SickK, G7140729675, Washington University Institute of Clinical and Translational Sciences, G742032275, Institute for Clinical and Translational Research, Institutional Clinical and Translational Science Award, G7691683386, G7901210138, G7989263, G801680829, G8162906845, G8452285102, G884570035, Childhood Liver Disease Research Network (ChiLDReN) Clinical Centers, Midwest Children's Consortium, Advancing our Understanding of Rare Pediatric Liver Diseases, G911253010, G984646292
OpenAlex ID: W2000669554