Use of corticosteroids after hepatoportoenterostomy for bile drainage in infants with biliary atresia: the START randomized clinical trial.
Use of corticosteroids after hepatoportoenterostomy for bile drainage in infants with biliary atresia: the START randomized clinical trial.
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DOI：
10.1001/jama.2014.2623
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发表时间：
2014-05-07
影响因子：
120.7
通讯作者：
Sokol, Ronald J.
中科院分区：
文献类型：
--
作者：
Bezerra, Jorge A.;Spino, Cathie;Magee, John C.;Shneider, Benjamin L.;Rosenthal, Philip;Wang, Kasper S.;Erlichman, Jessi;Haber, Barbara;Hertel, Paula M.;Karpen, Saul J.;Kerkar, Nanda;Loomes, Kathleen M.;Molleston, Jean P.;Murray, Karen F.;Romero, Rene;Schwarz, Kathleen B.;Shepherd, Ross;Suchy, Frederick J.;Turmelle, Yumirle P.;Whitington, Peter F.;Moore, Jeffrey;Sherker, Averell H.;Robuck, Patricia R.;Sokol, Ronald J.
胆道闭锁是儿童终末期肝病最常见的原因。对于肝门肠吻合术后使用类固醇是否能改善临床结果，仍存在争议。目的：确定肝门肠吻合术后加用大剂量糖皮质激素在改善胆道引流和自体肝脏存活率方面是否优于单纯手术。这项多中心、双盲的类固醇治疗胆道闭锁随机试验(START)于2005年9月至2011年2月期间在美国140名婴儿(平均年龄2.3个月)中进行；随访于2013年1月结束。受试者随机接受静脉注射甲基强的松龙(4 mg/kg/d，2周)和口服强的松龙(2 mg/kg/d，2周)，然后逐渐减少治疗9周(n=70)或在肝门肠吻合术后72小时内开始服用安慰剂(n=70)。主要终点(有能力检测25%的绝对治疗差异)是指在术后6个月血清总胆红素水平低于1.5 mg/dL的参与者与他/她的天然肝脏的百分比。次要结果包括24个月龄时使用天然肝脏存活和严重的不良事件。在术后6个月，类固醇治疗改善胆汁引流的参与者的比例没有统计学意义的改善(类固醇组58.6%[41/70]比安慰剂组48.6%[34/70]；调整后的相对危险度1.14[95%CI，0.83比1.57]；P=.43)。调整后的绝对风险差为8.7%(95%可信区间，−为10.4%~27.7%)。24个月龄时，类固醇组的无移植存活率为58.7%，安慰剂组为59.4%(调整后的风险比为1.0[95%可信区间，0.6至1.8]；P=0.99)。类固醇组和安慰剂组中有严重不良事件的参与者的比例分别为81.4%[57/70]和80.0%[56/70](P>；.99)；然而，接受类固醇治疗的参与者在术后30天出现第一次严重不良事件的时间较早(类固醇组37.2%[95%CI，26.9%至50.0%]，而安慰剂组19.0%[95%CI，11.5%至30.4%]；P=.008)。在胆道闭锁的婴儿接受肝门肠吻合术后，术后大剂量类固醇治疗在6个月时胆汁引流方面没有统计学意义上的差异，尽管不能排除小的临床益处。类固醇治疗与胆道闭锁儿童严重不良事件的早期发病有关。
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. 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. 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. 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. 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. 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). 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.
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