Acute liver failure Alginate Cell transplantation Cryopreservation Hepatocyte microbeads Intraperitoneal transplantation Microencapsulated human hepatocytes
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摘要

BACKGROUND & AIMS:Liver transplantation (LT) is the most effective treatment for patients with acute liver failure (ALF), but is limited by surgical risks and the need for life-long immunosuppression. Transplantation of microencapsulated human hepatocytes in alginate is an attractive option over whole liver replacement. The safety and efficacy of hepatocyte microbead transplantation have been shown in animal models. We report our experience of this therapy in children with ALF treated on a named-patient basis.
METHODS:Clinical grade human hepatocyte microbeads (HMBs) and empty microbeads were tested in immunocompetent healthy rats. Subsequently, 8 children with ALF, who were awaiting a suitable allograft for LT, received intraperitoneal transplantation of HMBs. We monitored complications of the procedure, assessing the host immune response and residual function of the retrieved HMBs, either after spontaneous native liver regeneration or at the time of LT.
RESULTS:Intraperitoneal transplantation of HMBs in healthy rats was safe and preserved synthetic and detoxification functions, without the need for immunosuppression. Subsequently, 8 children with ALF received HMBs (4 neonatal haemochromatosis, 2 viral infections and 2 children with unknown cause at time of infusion) at a median age of 14.5 days, range 1 day to 6 years. The procedure was well tolerated without complications. Of the 8 children, 4 avoided LT while 3 were successfully bridged to LT following the intervention. HMBs retrieved after infusions (at the time of LT) were structurally intact, free of host cell adherence and contained viable hepatocytes with preserved functions.
CONCLUSION:The results demonstrate the feasibility and safety of an HMB infusion in children with ALF.
LAY SUMMARY:Acute liver failure in children is a rare but devastating condition. Liver transplantation is the most effective treatment, but it has several important limitations. Liver cell (hepatocyte) transplantation is an attractive option, as many patients only require short-term liver support while their own liver recovers. Human hepatocytes encapsulated in alginate beads can perform the functions of the liver while alginate coating protects the cells from immune attack. Herein, we demonstrated that transplantation of these beads was safe and feasible in children with acute liver failure.

译文

背景与目的: 肝移植 (LT) 是急性肝衰竭 (ALF) 患者最有效的治疗方法,但受手术风险和终身免疫抑制需求的限制。微囊化人肝细胞在藻酸盐中的移植是整个肝脏替代的一个有吸引力的选择。肝细胞微珠移植的安全性和有效性已在动物模型中得到证明。我们报告了在指定患者基础上治疗的 ALF 患儿的这种治疗经验。
方法: 对免疫正常的健康大鼠进行临床级人肝细胞微珠 (HMBs) 和空微珠的检测。随后,8 名 ALF 儿童接受了 HMBs 腹腔移植,他们正在等待适合 LT 的同种异体移植。我们监测了手术的并发症,评估了自发天然肝再生后或 LT 时获得的 HMBs 的宿主免疫反应和残余功能。
结果: 健康大鼠腹腔移植 HMBs 是安全的,保留了合成和解毒功能,不需要免疫抑制。随后,8 名患有 ALF 的儿童接受了 HMBs (4 名新生儿血色病,2 名病毒感染和 2 名输液时原因不明的儿童),平均年龄为 14.5 天, 范围 1 天到 6 年。手术耐受性良好,无并发症。在 8 名儿童中,4 名避免了 LT,而 3 名在干预后成功桥接至 LT。输注后回收的 HMBs (在 LT 时) 结构完整,无宿主细胞粘附,并含有保留功能的活肝细胞。
结论: 结果证明了在儿童 ALF 中输注 HMB 的可行性和安全性。
总结: 儿童急性肝衰竭是一种罕见但毁灭性的疾病。肝移植是最有效的治疗方法,但它有几个重要的局限性。肝细胞移植是一个有吸引力的选择,因为许多患者只需要短期的肝脏支持,而他们自己的肝脏恢复。包裹在藻酸盐珠中的人肝细胞可以执行肝脏的功能,而藻酸盐涂层保护细胞免受免疫攻击。在此,我们证明了这些珠子的移植在急性肝衰竭的儿童中是安全可行的。

acute liver failure

消化 肝功能损害 疾病
概述  :  

急性肝衰竭(acute liver failure)多是由药物、肝毒性物质、病毒、酒精等因素诱发的一组临床综合征,病人肝功能急剧恶化,表现为意识障碍和凝血功能紊乱等,多见于中青年人,发病迅速病死率高。 病因和发病机制病因:在我国,引起肝衰竭的首要因素是乙型肝炎病毒,其引起的慢加急性(亚急性)肝衰竭最为常见。其他常见病因包括药物性肝损伤、病毒性肝炎、自身免疫性肝病及休克或低血压引起的缺血性肝损伤。然而仍有约15%的患者病因不明。 发病机制:涉及内毒素及细胞因子介导的免疫炎症损伤,肝微循环障碍,

acute 英 /əˈkjuːt/  美 /əˈkjuːt/

释义   adj. 严重的,[医] 急性的;敏锐的;激烈的;尖声的

例句   But in other situations, a liver transplant may be the only cure for acute liver failure. 但是在其他情况下,肝脏移植可能是急性肝衰竭的唯一治愈希望。

 

liver 英 /ˈlɪvə(r)/  美 /ˈlɪvər/

释义   n. 肝脏;生活者,居民

例句   Three weeks ago, it was discovered the cancer had spread to his liver. 三周前,发现癌细胞已扩散到了他的肝脏。

 

failure 英 /ˈfeɪljə(r)/  美 /ˈfeɪljər/

释义   n. 失败;故障;失败者;破产

例句   There were also several accidents mainly caused by engine failures on take-off.

还有一些事故主要是由起飞时引擎故障导致的。


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