Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO.
University of Michigan, Ann Arbor, MI.
J Pediatr Gastroenterol Nutr. 2019 Apr;68(4):495-501. doi: 10.1097/MPG.0000000000002256.
Biliary atresia (BA) is a progressive neonatal fibroinflammatory cholangiopathy. We hypothesized that intravenous immunoglobulin (IVIg) would be safe, feasible, acceptable, and efficacious for the treatment of BA. The primary objective of this study was to establish the feasibility, acceptability, and safety profile of IVIg administration after hepatoportoenterostomy (HPE) in BA. The secondary objective was to determine the treatment efficacy of IVIg based on good bile drainage and survival with the native liver.
A multicenter, prospective, open-labeled, phase I/IIA trial of IVIg was conducted, with 1 g/kg/dose of IVIg infused at 3-5, 30, and 60 days post-HPE, and subjects followed for 360 days post-HPE. Twenty-nine participants completed the study.
Administration of IVIg infusions was feasible and acceptable in 79%. None of the serious adverse events (SAEs) were directly related to IVIg infusions; however, 90% of participants had an SAE. Compared with a historical placebo-arm group, there was no significant increase in the proportion of IVIg participants with a serum total bilirubin <1.5 mg/dL at 90, 180, or 360 days post-HPE. Survival with the native liver in the IVIg participants showed no significant benefit over the historical placebo arm, with a difference at 360 days of -11.9% (IVIg: 58.6%, placebo: 70.5%; 90% UCB: 2.1%; P > 0.05).
Although IVIg infusions in infants with BA post-HPE were feasible, acceptable and safe, there was no trend to lower bilirubin levels or improved 360-day survival with the native liver.
Safety Study of Intravenous Immunoglobulin Post-Portoenterostomy in Biliary Atresia; #NCT01854827.
先天性胆道闭锁（BA）是一种进行性新生儿纤维炎症性胆管病。我们假设静脉注射免疫球蛋白（IVIg）用于治疗 BA 是安全、可行、可接受和有效的。本研究的主要目的是确定 BA 患儿行肝门空肠吻合术后（HPE）给予 IVIg 的可行性、可接受性和安全性。次要目的是根据良好的胆汁引流和保留自身肝脏的存活率来确定 IVIg 的治疗效果。
进行了一项多中心、前瞻性、开放性、I/IIA 期 IVIg 试验，在 HPE 后 3-5、30 和 60 天给予 1g/kg/d 的 IVIg 剂量，HPE 后随访 360 天。29 名参与者完成了该研究。
79%的参与者可接受 IVIg 输注，且输注是可行的。无严重不良事件（SAE）与 IVIg 输注直接相关；然而，90%的参与者发生了 SAE。与历史安慰剂组相比，IVIg 组 HPE 后 90、180 和 360 天血清总胆红素<1.5mg/dL 的比例没有显著增加。IVIg 组保留自身肝脏的存活率与历史安慰剂组相比没有显著获益，360 天时差异为-11.9%（IVIg：58.6%，安慰剂：70.5%；90% UCB：2.1%；P>0.05）。
尽管 HPE 后 BA 婴儿给予 IVIg 输注是可行、可接受和安全的，但没有降低胆红素水平或改善 360 天保留自身肝脏的存活率的趋势。
静脉免疫球蛋白在胆道闭锁术后的安全性研究；#NCT01854827。
