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活体肝移植中 ABO 血型屏障的挑战。

Challenge to ABO blood type barrier in living donor liver transplantation.

机构信息

Department of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.

出版信息

Hepatobiliary Pancreat Dis Int. 2020 Aug;19(4):342-348. doi: 10.1016/j.hbpd.2020.06.017. Epub 2020 Jun 30.

Abstract

ABO incompatible living donor liver transplantation has the potential to expand the donor pool for patients with end stage liver diseases on the expense of challenges to overcome immunological barriers across blood type. There is a profound impact of age on incidence and severity of antibody mediated rejection (AMR). Even children older than 1 year have chances of AMR; children aged 8 years or older have risks of hepatic necrosis similar to adult liver recipients. The mechanism of AMR is based on circulatory disturbances secondary to inflammation and injury of the vascular endothelium caused by an antibody-antigen-complement reaction. The strategy to overcome ABO blood type barrier is based on both pre-transplant desensitization and adequate treatment of this phenomenon. Nowadays, rituximab is the standard means of desensitization but unfortunately an insufficient aid to treat AMR. Because of low incidence (less than 5% in the rituximab era), in practice of AMR only some case reports about the treatment of clinical AMR are available in the literature. Initial experiences revealed that the proteasome inhibitor, bortezomib might be a promising treatment based on its capacity to deplete plasma cell agents. Although ABO blood type barrier has been counteracted in 95% of patients by applying "rituximab-desensitization", many issues, such as prediction of high-risk patients of infection and AMR and secure treatment strategies for evoked AMR, remain to be resolved.

摘要

ABO 不相容活体供肝移植有可能扩大终末期肝病患者的供体库,但需要克服血型免疫屏障的挑战。年龄对抗体介导的排斥反应(AMR)的发生率和严重程度有深远影响。即使是 1 岁以上的儿童也有发生 AMR 的机会;年龄在 8 岁或以上的儿童发生肝坏死的风险与成人肝受体相似。AMR 的机制基于循环障碍,是由抗体-抗原-补体反应引起的血管内皮炎症和损伤所致。克服 ABO 血型障碍的策略基于移植前脱敏和对此现象的充分治疗。如今,利妥昔单抗是脱敏的标准手段,但不幸的是,它对 AMR 的治疗帮助不足。由于发病率低(在利妥昔单抗时代不到 5%),实际上,文献中只有一些关于治疗临床 AMR 的病例报告。初步经验表明,蛋白酶体抑制剂硼替佐米可能是一种有前途的治疗方法,因为它能够消耗浆细胞。尽管通过“利妥昔单抗脱敏”,已经有 95%的患者克服了 ABO 血型障碍,但仍有许多问题需要解决,如预测感染和 AMR 的高危患者,以及为诱发的 AMR 制定安全的治疗策略。

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