Makowa L, Cramer D V, Hoffman A, Breda M, Sher L, Eiras-Hreha G, Tuso P J, Yasunaga C, Cosenza C A, Wu G D
Department of Surgery and Transplantation Services, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Transplantation. 1995 Jun 27;59(12):1654-9. doi: 10.1097/00007890-199506270-00002.
A 26-year-old female patient with fulminant hepatic failure and a history of autoimmune hepatitis was heterotopically transplanted with a pig hepatic xenograft to provide temporary metabolic support prior to transplantation with a human donor organ. Circulating natural antipig antibodies were removed prior to transplantation by plasmapheresis and ex vivo en bloc perfusion of the donor pig kidneys. The liver xenograft functioned after transplantation as measured by active bile production, stabilization of prothrombin levels, and reduction in the circulating levels of lactic acid and the enzymes AST and ALT. Despite the removal of greater than 90% of the recipient's natural xenoantibodies prior to transplantation, the levels of antibody rapidly returned and were associated with antibody and complement-mediated rejection of the donor graft. Immunohistochemical evidence of graft rejection could be detected by the deposition of antibody, complement components including properdin, and endothelial swelling as early as 3 hr posttransplantation. These lesions progressed in severity and were accompanied by evidence of thrombosis and ischemic necrosis of the liver xenograft by 34 hrs posttransplantation. The main portal vein, hepatic artery, and vena cava were patent. The placement of the liver graft did not result in any improvement in the neurological status of the patient and she died 34 hr after xenografting due to irreversible brain damage. The information derived from this case has renewed interest in the clinical use of bioartificial devices and whole organ perfusion using xenogeneic tissue for temporary bridging of patients prior to allografting.
一名26岁的女性患者,患有暴发性肝衰竭且有自身免疫性肝炎病史,在接受人类供体器官移植前,接受了猪肝脏异种移植以提供临时代谢支持。在移植前,通过血浆置换和供体猪肾脏的体外整体灌注去除循环中的天然抗猪抗体。移植后,肝脏异种移植物发挥了功能,表现为有活跃的胆汁分泌、凝血酶原水平稳定以及循环中乳酸水平和酶AST及ALT降低。尽管在移植前已去除受体超过90%的天然异种抗体,但抗体水平迅速回升,并与供体移植物的抗体和补体介导的排斥反应相关。早在移植后3小时,通过抗体沉积、包括备解素在内的补体成分以及内皮肿胀等免疫组织化学证据即可检测到移植物排斥反应。这些病变严重程度逐渐加重,到移植后34小时,伴有肝脏异种移植物血栓形成和缺血坏死的证据。主要门静脉、肝动脉和腔静脉通畅。肝脏移植物的植入并未使患者的神经状态有任何改善,患者在异种移植后34小时因不可逆转的脑损伤死亡。该病例所获得的信息重新激发了人们对生物人工装置的临床应用以及使用异种组织进行全器官灌注以在同种异体移植前为患者进行临时桥接的兴趣。