Millis J M, Alonso E M, Piper J B, Bruce D S, Newell K A, Woodle E S, Baker A L, Whitington P F, Thistlethwaite J R
Sections of Transplantation, Pediatric Gastroenterology, Hepatology and Nutrition, and the Gastroenterology/Liver Study Unit, University of Chicago, Illinois, USA.
Clin Transpl. 1995:187-97.
Over the past 5 years, we have employed several strategies to increase the donor pool for both the pediatric and adult populations. The innovative expansion of the donor pool with the use living-related donors for children and cadaveric, high-risk donors for adults has increased our ability to serve our recipients and transplant them at an earlier stage in the disease process, thereby improving survival. As Hepatitis C is now the leading indication for liver transplantation in the adult population, the investigation of the natural history of Hepatitis C prior to and after transplantation provides a major challenge and is currently a focus of both laboratory and clinical efforts. For those recipients of Hepatitis C-positive-donor livers, determining the role of recipient and donor genotypes in the progression of recurrent hepatitis should help define the proper utilization of these organs. For patients on CsA-based immunosuppression regimens who experience steroid-resistant rejection, tacrolimus has proved to be extremely effective in reversing the rejection episodes and maintaining normal graft function. The long-term results of this therapy appear to be superior to OKT3 therapy. The recipients of living-related liver transplantation continue to have a survival advantage in comparison to recipients of cadaveric grafts. The donor operation can be routinely performed with minimal risk. Because of the superior results achieved and minimal donor risks, we feel that providing the option of living-donor transplantation is ethically justified, and medically necessary. Despite the encouraging results from living-donor transplantation, unexpected complications including portal vein complications and hepatic artery thrombosis have forced technical modifications of the original technique which may have implications to pediatric liver transplantation in general. As the volume of pediatric liver transplants and the number of immmunosuppressive regimens have increased over the years, posttransplant lymphoproliferative disease has been identified as a problem which requires more inspection. We have determined that the severity of rejection and the subsequent treatment, and primary Epstein-Barr virus are the primary risk factors for developing of PTLD. Identification of the risk factors and early detection may provide some hope for treatment of the disease while allowing long-term graft function. Results of our preliminary data show that, following transplantation, 3/4 of the children or parents report minimal impairment with regard to developmental or physical milestones. Patients and their families, however, continue to report significant levels of stress in their lives and occasional pain. Further research on outcome needs to be performed on our pediatric recipients to ensure the long-term benefit of our efforts.
在过去5年里,我们采用了多种策略来扩大儿科和成人的供体库。通过创新方式扩大供体库,利用儿童的活体亲属供体以及成人的尸体、高风险供体,提高了我们为受者服务并在疾病进程早期为其进行移植的能力,从而提高了生存率。由于丙型肝炎目前是成人肝移植的主要适应证,对丙型肝炎移植前后自然史的研究带来了重大挑战,目前是实验室和临床工作的重点。对于那些接受丙型肝炎阳性供体肝脏的受者,确定受者和供体基因型在复发性肝炎进展中的作用,应有助于明确这些器官的合理利用。对于接受基于环孢素免疫抑制方案且发生类固醇抵抗性排斥反应的患者,他克莫司已被证明在逆转排斥反应发作和维持移植肝功能正常方面极为有效。这种治疗的长期效果似乎优于OKT3治疗。与尸体移植受者相比,活体亲属肝移植受者的生存率仍具有优势。供体手术可常规进行,风险极小。鉴于取得的优异结果和供体极小的风险,我们认为提供活体供体移植选择在伦理上是合理的,在医学上也是必要的。尽管活体供体移植取得了令人鼓舞的结果,但包括门静脉并发症和肝动脉血栓形成在内的意外并发症迫使对原始技术进行技术改进,这可能对一般儿科肝移植产生影响。随着多年来儿科肝移植数量和免疫抑制方案数量的增加,移植后淋巴细胞增生性疾病已被确认为一个需要更多检查的问题。我们已经确定,排斥反应的严重程度及后续治疗以及原发性EB病毒是发生移植后淋巴细胞增生性疾病的主要危险因素。识别这些危险因素并早期发现,可能为该疾病的治疗带来一些希望,同时维持移植肝功能长期正常。我们初步数据的结果显示,移植后,四分之三的儿童或其父母报告在发育或身体里程碑方面仅有轻微损害。然而,患者及其家人继续报告生活中存在显著压力水平和偶尔的疼痛。需要对我们的儿科受者进行进一步的结局研究,以确保我们的努力能带来长期益处。