Use of Corticosteroids After Hepatoportoenterostomy for Bile Drainage in Infants With Biliary Atresia The START Randomized Clinical Trial

被引:151
作者
Bezerra, Jorge A. [1 ]
Spino, Cathie [2 ]
Magee, John C. [2 ]
Shneider, Benjamin L. [3 ]
Rosenthal, Philip [4 ]
Wang, Kasper S. [5 ,6 ]
Erlichman, Jessi [7 ]
Haber, Barbara [7 ]
Hertel, Paula M. [8 ,9 ]
Karpen, Saul J. [10 ,11 ]
Kerkar, Nanda [12 ]
Loomes, Kathleen M. [7 ]
Molleston, Jean P. [13 ,14 ]
Murray, Karen F. [15 ]
Romero, Rene [10 ,11 ]
Schwarz, Kathleen B. [16 ]
Shepherd, Ross [8 ,9 ]
Suchy, Frederick J. [17 ,18 ]
Turmelle, Yumirle P. [19 ]
Whitington, Peter F. [20 ]
Moore, Jeffrey [2 ]
Sherker, Averell H. [21 ]
Robuck, Patricia R. [21 ]
Sokol, Ronald J. [17 ,18 ]
机构
[1] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA
[2] Univ Michigan, Ann Arbor, MI 48109 USA
[3] UPMC, Childrens Hosp Pittsburgh, Pittsburgh, PA USA
[4] UCSF Benioff Childrens Hosp, San Francisco, CA USA
[5] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA
[6] Univ So Calif, Los Angeles, CA USA
[7] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA
[8] Baylor Coll Med, Houston, TX 77030 USA
[9] Texas Childrens Hosp, Houston, TX 77030 USA
[10] Emory Univ, Sch Med, Atlanta, GA USA
[11] Childrens Healthcare Atlanta, Atlanta, GA USA
[12] Mt Sinai Sch Med, New York, NY USA
[13] Indiana Univ Sch Med, Indianapolis, IN 46202 USA
[14] Riley Hosp Children, Indianapolis, IN USA
[15] Seattle Childrens Hosp, Seattle, WA USA
[16] Johns Hopkins Univ, Sch Med, Baltimore, MD USA
[17] Univ Colorado, Sch Med, Aurora, CO USA
[18] Childrens Hosp Colorado, Aurora, CO USA
[19] Washington Univ, Sch Med, St Louis, MO USA
[20] Lurie Childrens Hosp Chicago, Chicago, IL USA
[21] NIDDK, NIH, Bethesda, MD 20892 USA
来源
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION | 2014年 / 311卷 / 17期
关键词
ADJUVANT STEROID-THERAPY; KASAI PORTOENTEROSTOMY; OUTCOMES; MANAGEMENT; IMPROVE; FLOW;
D O I
10.1001/jama.2014.2623
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
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.
引用
收藏
页码:1750 / 1759
页数:10
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