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ABO血型不相容的活体供肝移植的治疗策略及治疗性血液成分单采疗法的作用

Therapeutic strategy and the role of apheresis therapy for ABO incompatible living donor liver transplantation.

作者信息

Kozaki Koichi, Egawa Hiroto, Kasahara Mureo, Oike Fumitaka, Yoshizawa Atsushi, Fukatsu Atsushi, Tanaka Koichi

机构信息

Department of Transplantation Immunology, Faculty of Medicine, Kyoto University, Kyoto, Japan.

出版信息

Ther Apher Dial. 2005 Aug;9(4):285-91. doi: 10.1111/j.1744-9987.2005.00304.x.

DOI:10.1111/j.1744-9987.2005.00304.x
PMID:16076368
Abstract

Although in Japan, transplant organs obtained from brain-dead donors (BDD) has been allowed since October 1997, to date only 27 liver grafts from BDD have been obtained. The severe shortage of transplantable organs is a big problem, not only in liver transplantation but also other organ transplants. Liver transplantation is a fundamental treatment for end-stage liver disease. In order to perform living-donor liver transplantation (LDLT) in a safer manner, apheresis (plasmapheresis) plays a major role in Japan because of the prevalence of LDLT wherein later re-transplantation is difficult. Therefore, because of a limited donor supply and because the need of patients with end-stage liver disease is critical, use of grafts from ABO-incompatible donors may be the only available option. From June 1990 to November 2004, 1010 patients underwent 1060 LDLT cases at Kyoto University Hospital. Of these, 139 LDLT cases (13.1%) received ABO-incompatible living-donor liver grafts. The role of apheresis in ABO-incompatible LDLT is the reduction of antibody titers such as anti-A or anti-B antibody. We perform preoperative apheresis as a general rule for incompatible cases, and the recipient's antibody level against the donor's blood type is decreased to one eighth of the baseline value before LDLT. Up to the present, baseline antirejection regimens included steroids, tacrolimus and cyclophosphamide. At first, splenectomy was performed during operation to suppress antibody production, and intraportal infusion therapy was performed to control local disseminated intravascular coagulation (DIC) occurring in ABO-incompatible grafts. At that time, three agents--methylprednisolone, prostaglandin E1, and gabexate mesilate--were infused continuously for 3 weeks after LDLT. At present, instead of intraportal infusion therapy, hepatic artery infusion therapy without splenectomy is adopted because of portal thrombosis, and two agents--methylprednisolone and prostaglandin E1--are infused continuously for 3 weeks after LDLT. Recently, we introduced an anti-CD20 monoclonal antibody (Rituximab) instead of splenectomy for B cell deletion before ABO-incompatible LDLT. In this article, we describe our therapeutic strategy and the role of apheresis around ABO-incompatible LDLT.

摘要

尽管在日本,自1997年10月起已允许使用脑死亡供体(BDD)的移植器官,但迄今为止,仅获得了27例来自脑死亡供体的肝移植。可移植器官的严重短缺不仅是肝移植面临的大问题,也是其他器官移植面临的大问题。肝移植是终末期肝病的基本治疗方法。为了更安全地进行活体肝移植(LDLT),由于LDLT的普遍性(后期再移植困难),血液成分分离术(血浆置换)在日本发挥着重要作用。因此,由于供体供应有限且终末期肝病患者的需求迫切,使用ABO血型不相合供体的移植物可能是唯一可行的选择。1990年6月至2004年11月,京都大学医院有1010例患者接受了1060例LDLT手术。其中,139例LDLT手术(13.1%)接受了ABO血型不相合的活体肝移植物。血液成分分离术在ABO血型不相合的LDLT中的作用是降低抗体滴度,如抗A或抗B抗体。对于不相合病例,我们通常在术前进行血液成分分离术,使受者针对供者血型的抗体水平在LDLT前降至基线值的八分之一。到目前为止,基线抗排斥方案包括类固醇、他克莫司和环磷酰胺。起初,手术中进行脾切除术以抑制抗体产生,并进行门静脉内输注治疗以控制ABO血型不相合移植物中发生的局部弥散性血管内凝血(DIC)。当时,在LDLT后连续3周持续输注三种药物——甲泼尼龙、前列腺素E1和甲磺酸加贝酯。目前,由于门静脉血栓形成,采用不进行脾切除术的肝动脉输注治疗代替门静脉内输注治疗,并且在LDLT后连续3周持续输注两种药物——甲泼尼龙和前列腺素E1。最近,我们引入了一种抗CD20单克隆抗体(利妥昔单抗)代替脾切除术,用于在ABO血型不相合的LDLT前清除B细胞。在本文中,我们描述了我们的治疗策略以及血液成分分离术在ABO血型不相合的LDLT中的作用。

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