Starzl T E, Fung J, Tzakis A, Todo S, Demetris A J, Marino I R, Doyle H, Zeevi A, Warty V, Michaels M
Pittsburgh Transplant Institute, Pennsylvania.
Lancet. 1993 Jan 9;341(8837):65-71. doi: 10.1016/0140-6736(93)92553-6.
Our ability to control both the cellular and humoral components of xenograft rejection in laboratory experiments, together with an organ shortage that has placed limits on clinical transplantation services, prompted us to undertake a liver transplantation from a baboon to a 35-year-old man with B virus-associated chronic active hepatitis and human immunodeficiency virus infection. Liver replacement was performed according to conventional surgical techniques. Immunosuppression was with the FK 506-prednisone-prostaglandin regimen used routinely for hepatic allotransplantation, to which a daily non-myelotoxic dose of cyclophosphamide was added. During 70 days of survival, there was little evidence of hepatic rejection by biochemical monitoring or histopathological examination. Products of hepatic synthesis, including clotting factors, became those of the baboon liver with no obvious adverse effects. Death followed a cerebral and subarachnoid haemorrhage that was caused by an angioinvasive aspergillus infection. However, the underlying cause of death was widespread biliary sludge that formed in the biliary tree despite a seemingly satisfactory choledochojejunostomy. During life and in necropsy samples, there was evidence of the chimerism that we believe is integral to the acceptance of both xenografts and allografts. Our experience has shown the feasibility of controlling the rejection of the baboon liver xenograft in a human recipient. The biliary stasis that was the beginning of lethal infectious complications may be correctable by modifications of surgical technique. In further trials, the error of over-immunosuppression should be avoidable.
在实验室实验中,我们有能力控制异种移植排斥反应的细胞和体液成分,再加上器官短缺限制了临床移植服务,促使我们对一名患有B病毒相关性慢性活动性肝炎和人类免疫缺陷病毒感染的35岁男性进行了狒狒肝脏移植。肝脏置换按照常规手术技术进行。免疫抑制采用肝同种异体移植常规使用的FK 506-泼尼松-前列腺素方案,并每日添加非骨髓毒性剂量的环磷酰胺。在存活的70天里,通过生化监测或组织病理学检查几乎没有肝排斥反应的证据。包括凝血因子在内的肝脏合成产物变成了狒狒肝脏的产物,且没有明显的不良反应。死亡原因是由血管侵袭性曲霉菌感染引起的脑和蛛网膜下腔出血。然而,死亡的根本原因是尽管胆总管空肠吻合术看似令人满意,但胆管树中仍形成了广泛的胆泥。在生前和尸检样本中,有证据表明存在嵌合体,我们认为这是异种移植和同种异体移植被接受的不可或缺的因素。我们的经验表明,在人类受者中控制狒狒肝脏异种移植排斥反应是可行的。作为致命感染并发症开端的胆汁淤积,或许可通过手术技术的改进来纠正。在进一步的试验中,应该可以避免过度免疫抑制的错误。