再次肝移植的长期生存

移植肝功能丧失的唯一治疗是再移植，但有不少供体、受者和手术等方面的因素影响其最终结局，为此作者复习了Dumont－UCLA移植中心于1984～1996年所施行肝移植2057次（1701例病人）的资料，着重对299例病人356次再度肝移植的生存率进行分析，其中250例接受2次肝移植，43例接受3次，6例接受3次以上。成人接受移植时的年龄72．2％为18岁或以下。同时取150例仅移植1次的病例作为对照，按相拟年龄、相近移植时间和受体器官分配联网状态（UNOS）进行病例-对照研究，应用多变量回归分析评估与生存率有关的因素。结果（一）再次移植病人的生存…     

再次肝移植

在首次移植失败后,再次肝脏移植是挽救移植肝失功受体病人生命的唯一手段。随着肝移植受体数量的积累,再次肝移植的数量也必将越来越多,再次肝移植越来越成为一个令人关注的问题。近年来随着供体紧缺和新型免疫抑制剂的研发,再次肝移植的适应证发生了明显变化,而总的再移植发生率逐步下降。严格评估再次肝移植术前受体的状况,充分考虑再次肝移植的危险因素对提高再次肝移植术后的生存率尤为重要。手术时机和适应证的正确把握、手术技巧的提高是再次肝移植手术成功和提高术后生存率的关键。     

肝移植免疫抑制治疗临床应用进展

自从开展器官移植以来,外科手术技术和免疫抑制治疗发生了巨大变化。在过去十年中,排斥反应和移植物失功发生率已明显下降。目前,应用免疫抑制剂的长期并发症已取代排斥反应成为移植治疗的主要挑战。与肾移植和心脏移植相比,肝移植术后急性排斥反应发生率并不高,并且对移植物存活的影响较小,但不合理使用免疫抑制剂也会导致移植失败。如何诱导产生稳定而持久的免疫耐受,适当的免疫调节治疗将是肝移植良好开展的主要保证。本文拟对免疫抑制剂的种类、应用情况和目前的治疗进展进行综述,并探讨肝移植免疫抑制治疗的前景。     

公民逝世后器官捐献肝移植78例临床经验分析

目的总结公民逝世后器官捐献肝移植的临床经验及疗效分析。方法回顾性分析2012年3月至2015年11月四川大学华西医院肝脏移植中心完成的公民逝世后器官捐献供体肝移植的76例供体和78例受体的临床资料。观察肝移植受体早期移植物功能恢复情况并分析引起早期移植物功能障碍(EAD)的危险因素,观察远期的移植物生存及受体生存情况、并发症发生情况。结果 78例受体术后EAD的发生率为36%(28/78),其中供体总胆红素(TB)高和冷缺血时间长是EAD发生的危险因素。受者围手术期存活率为92%(72/78),死亡6例,分别死于原发性移植物失功4例、上消化道大出血1例、肺部感染1例。术后发生腹腔感染5例,胆道狭窄3例,血管血栓形成2例,除1例死亡外,其余经相应治疗后好转。受体术后1年的存活率为84.2%,2年存活率为80.0%。结论公民逝世后器官捐献供肝是较好的供肝来源,其近远期效果良好。控制术前供肝质量,缩短冷缺血时间等均是提高临床效果的重要措施。     

移植肝冷保存/再灌注胆管损伤的机制

肝移植术后胆道的生理及病理变化一直是众所关注的课题。胆道并发症是影响肝移植受者术后生活质量、导致移植物丧失甚至病人死亡的重要因素，总体发生率为5．8％-40.0％，而对于某些特殊类型的肝移植，如活体右半肝移植的胆道并发症发生率可高达15％-64％，儿童肝移植胆道并发症的发生率也明显为高。近年来，随着移植技术的进步和新型免疫抑制剂的使用，受者及移植物的短期存活率有了显著提高，但长期生存率依然没有明显的改善，而胆道并发症被认为是导致这一结果的最主要原因之一。     

肝移植后免疫抑制剂的减量与撤除

肝脏移植是终末期肝病唯一有效的治疗手段,但移植后的排斥反应仍然可以导致移植物的短期内丢失.免疫抑制剂的应用虽可有效阻止移植物早期发生排斥反应,但在肝移植的中后期,免疫抑制剂的长期应用导致的感染、肾毒性、神经毒性、骨髓抑制等不良反应也不容忽视.考虑到长期大量应用免疫抑制剂的危害,近年来,肝移植后免疫抑制剂的减量和撤除倍受关注,免疫抑制剂的应用也由浓度导向悄然向依赖于受体免疫状态的个体化治疗转变.随着基础和临床研究的深入,免疫抑制剂的减量与撤除虽已在临床逐步开展,但同样也面临诸多问题.     

血管内皮细胞生长因子在排斥反应中的作用的研究进展

器官移植如今已成为治疗某器官因严重病损而致功能衰竭的重要手段。虽然随着外科技术的进步、器官保存方法的提高以及新的免疫抑制剂的出现，同种异体移植的生存率得到了明显提高，但术后排斥反应仍是移植物失功和需再次移植的主要原因之一，因此排斥反应成为当前器官移植界亟待解决的一个重要问题。     

近期移植肾失功再移植的体会

我院１９９３年１月至１９９４年１０月为２０６例慢性肾炎晚期尿毒症病人进行尸体肾肾移植术，其中３例病人早期移植肾功，经正确的临床判断，及时摘除失功肾并行再移植获得成功。术后随访半年１例，１年以上２例均未出现排斥反应及并发症，移植肾功能正常。本文对早期失功的原因，再移植时机，手术方法及术手型免疫抑制剂的应用等进行了讨论。     

后期肝移植物失功的诊断和治疗进展

随着外科手术技术的改进,术后处理措施的不断完善,以及越来越有效的免疫抑制药物的临床应用,肝移植的临床效果已显著改善〔1〕。在许多国家和地区,目前肝移植已成为治疗多种终末期肝病的常规方法,绝大多数受体病人能获得长期存活。然而,肝移植外科医师和肝病专家仍面临肝移植术后许多并发症的严重挑战,其中之一是后期肝移植物失功(LHAD)。LHAD可引起移植肝功能障碍,需再次肝移植,甚至可导致病人死亡。本文就LHAD的主要病因的诊断和治疗进展综述如下。一、LHAD的病因肝移植物失功按时间可分为两种类型:早期移植物失功(EHAD),发生于肝…     

器官移植后恶性肿瘤的发生

<正>在移植受者死亡的主要原因为免疫或非免疫因素引起的移植物失功的阶段,恶性肿瘤的发生仅仅被认为是移植后的一种并发症。随着新型免疫抑制剂和免疫抑制方案的应用,急性排斥反应以及相应的移植物丢失率明显降低,     

Long-term survival after liver transplantation in 4,000 consecutive patients at a single center

OBJECTIVE: To evaluate the long-term survival outcomes of a large cohort of liver transplant recipients and to identify static and changing factors that influenced these outcomes over time. SUMMARY BACKGROUND DATA: Liver transplantation has been accepted as a therapeutic option for patients with end-stage liver disease since 1983, with continual improvements in patient survival as a result of advances in immunosuppression and medical management, technical achievements, and improvements in procurement and preservation. Although many reports, including registry data, have delineated short-term factors that influence survival, few reports have examined factors that affect long-term survival after liver transplantation. METHODS: Four thousand consecutive patients who underwent liver transplantation between February 1981 and April 1998 were included in this analysis and were followed up to March 2000. The effect of donor and recipient age at the time of transplantation, recipient gender, diagnosis, and year of transplantation were compared. Rates of retransplantation, causes of retransplantation, and cause of death were also examined. RESULTS: The overall patient survival for the entire cohort was 59%; the actuarial 18-year survival was 48%. Patient survival was significantly better in children, in female recipients, and in patients who received transplants after 1990. The rates of retransplantation for acute or chronic rejection were significantly lower with tacrolimus-based immunosuppression. The risk of graft failure and death was relatively stable after the first year, with recurrence of disease, malignancies, and age-related complications being the major factors for loss. CONCLUSION: Significantly improved patient and graft survival has been observed over time, and graft loss from acute or chronic rejection has emerged as a rarity. Age-related and disease-related causes of graft loss represent the greatest threat to long-term survival.     

Long-term survival and late graft loss in pediatric liver transplant recipients—a 15-year single-center experience

Increasing numbers of children undergo successful liver transplantation. Limited data exist on long-term survival and late graft loss. Survival and graft loss were studied in 376 primary liver graft recipients who survived more than 3 months after transplantation (80.5% of all primary graft recipients). Patient records were reviewed retrospectively for causes of graft loss. Risk factors were identified by analyzing graft, recipient, and posttransplant variables using multivariate Cox regression. One-, 5-, and 10-year actuarial graft survival rates in the study population were 94.6%, 87.3%, and 86.3%, respectively. Corresponding patient survival rates were 95.7%, 91.4%, and 90.4%. Forty-seven (12.5%) grafts were lost subsequently, 15 by patient death with preserved graft function. Survival rate after late retransplantation was 63.3%. Causes of late graft loss were infection (21.2%), posttransplant lymphoproliferative disease (PTLD, 21.2%), chronic rejection (17%), biliary complications (14.8%), and recurrence of malignant disease (8.5%). Independent risk factors for late graft loss and patient death included liver malignancy as primary disease, steroid resistant rejection, and PTLD. Graft loss rate was significantly increased for reduced-size grafts. Patients undergoing transplantation after 1991 and recipients of full-size grafts were more likely to survive. In conclusion, the long-term outcome for pediatric primary liver graft recipients surviving the early postoperative period is excellent except for patients with liver malignancy. There is no increased risk of late graft loss with the use of split or living related donor grafts. Technical complications are only a minor factor in late graft loss, but complications related to immunosuppression and infection remain a major hazard and must be addressed. (Liver Transpl 2002;8:615-622.)     

Pediatric liver transplantation. A single center experience spanning 20 years

BACKGROUND: Survival after liver transplantation has improved significantly over the last decade with pediatric recipients faring better than adults. The 20-year experience of pediatric liver transplantation at Children's Hospital of Pittsburgh is reported in terms of patient survival; graft survival in relation to age, gender, and immunosuppressive protocols; causes of death; and indications for retransplantation. METHOD: From March 1981 to April 1998, 808 children received liver transplants at Children's Hospital of Pittsburgh. All patients were followed until March 2001, with a mean follow-up of 12.2+/-3.9 years (median=12.6; range=2.9-20). There were 405 female (50.2%) and 403 male (49.8%) pediatric recipients. Mean age at transplant was 5.3+/-4.9 years (mean=3.3; range 0.04-17.95), with 285 children (25.3%) being less than 2 years of age at transplant. Cyclosporine (CsA)-based immunosuppression was used before November 1989 in 482 children (50.7%), and the subsequent 326 recipients (40.3%) were treated with tacrolimus-based immunosuppression. Actuarial survival was calculated using the Kaplan-Meier statistical method. Differences in survival were calculated by log-rank analysis. RESULTS: Overall patient survival at 1, 5, 10, 15, and 20 years was 77.1%, 72.6%, 69.4%, 65.8%, and 64.4%, respectively. There was no difference in survival for male or female patients at any time point. At up to 10 years posttransplant, the survival for children greater than 2 years of age (79.5%, 75.7%, and 71.6% at 1, 5, and 10 years, respectively) was slightly higher than those at less than 2 years of age (72.6%, 66.9%, and 65.3% at 1, 5, and 10 years, respectively). However, at 15 and 20 years posttransplant, survival rates were similar (>2 years=67.3% and 65.8%; <2 years=64.1% and 64.1%). A significant difference in survival was seen in CsA-based immunosuppression (71.2%, 68.1%, 65.4%, and 61%) versus tacrolimus-based immunosuppression (85.8%, 84.7%, 83.3%, and 82.9%) at 1, 3, 5, and 10 years, respectively (P=0.0001). The maximum difference in survival was noted in the first 3 months between CsA and tacrolimus; thus, indicating there may have been other factors (nonimmunological factors) involved in terms of donor and recipient selection and technical issues. The mean annual death rate beyond 2 years posttransplant was 0.47%, with the mean annual death rate for patients who received tacrolimus-based immunosuppression being significantly lower than those who received CsA-based immunosuppression (0.14% vs. 0.8%; P=0.001). The most common etiologies of graft loss were hepatic artery thrombosis (33.4%), acute or chronic rejection (26.6%), and primary nonfunction (16.7%). Of note, retransplantation for graft loss because of acute or chronic rejection occurred only in those patients who received CsA-based immuno-suppression. CONCLUSION: The overall 20-year actuarial survival for pediatric liver transplantation is 64%. Survival has increased by 20% in the last 12 years with tacrolimus-based immunosuppression. Although this improvement may be the result of several factors, retransplantation as a result of acute or chronic rejection has been completely eliminated in patients treated with tacrolimus.     

Kidney Retransplantation Outcomes: A Paired Recipient Control Study

BackgroundDespite progressive improvements in graft and patient survival after kidney transplantation over the last decades, an increasing number of patients are waitlisted for retransplantation. Identifying the risk factors for second graft failure can help us improve management for such patients. The aim of this study was to compare the outcomes of kidney retransplantation with those of first transplantation.MethodsThis retrospective study included all the recipients of a second kidney transplant between January 2008 and December 2019. For each patient with a second kidney transplant, we selected the paired recipient from the same donor. We excluded recipients of donations from living donors, patient-and-donor pairs with more than 1 transplant, and patients without a pair. The follow-up took place December 31, 2020. We included 152 patients, corresponding to 76 pairs of recipients.ResultsPatients who underwent a second transplant had significantly higher panel reactive antibody values and longer waiting time for retransplantation. Biopsy-proven acute rejection episodes were doubled in patients undergoing a second transplant (P = .12). There was a lower survival of second grafts at the first, fifth, and 10th year (P < .05). The main factor influencing graft loss for both groups was acute rejection, and, in patients, with a second transplant, acute rejection increased the risk of graft loss by 17 times (odds ratio, 17.5; 95% confidence interval, 4.19-98).ConclusionsThe clinical results of second kidney transplants still fall short of first transplants, with the main factor of poor prognosis being acute rejection. In young patients, allocation and immunosuppression management should consider this risk to improve long-term outcomes.     

Survival after pediatric liver transplantation: why does living donation offer an advantage?

HYPOTHESIS: Living donor liver transplantation (LDLT) results in improved survival compared with deceased whole and split organ transplantation in children. OBJECTIVE: To evaluate the effect of LDLT on graft and patient survival in pediatric liver transplantation. DESIGN: Retrospective cohort. METHODS: Data included all pediatric recipients (aged <18 years) registered in the UNOS (United Network for Organ Sharing) database from October 1, 1987, to May 24, 2004. Covariates predictive of survival by univariate analyses were included in the Cox proportional hazards regression models in a blockwise fashion to determine predictors of survival. RESULTS: Kaplan-Meier graft and patient survival rates were improved in LDLT recipients compared with recipients of deceased whole and split organ transplantations (P<.01). In the initial model (model P<.001), prognostic factors for graft and patient survival included recipient age, race, origin of liver disease, certain pretransplantation laboratory data, medical condition, multiorgan transplantation, retransplantation, recipient-donor ABO blood compatibility, and cold and warm ischemia times. The addition of graft type to the initial covariate set did not significantly change the model (P = .21, covariate P = .09). However, most of the positive prognostic factors identified in the model were inherent characteristics of LDLT recipients and the LDLT procedure. CONCLUSIONS: Graft and patient survival in the pediatric population is better with LDLT than deceased organ transplantation. Factors that contribute to this difference include recipients who are less ill, who have shorter cold and warm ischemia times, and those with a decreased need for retransplantation but not the type of graft per se.     

Stable kidney function in the second decade after kidney transplantation while on cyclosporine-based immunosuppression

BACKGROUND: Calcineurin inhibitors (CNIs) have been the mainstay of immunosuppressive protocols in kidney transplantation over the past 20 years. However, in some recipients, the adverse effects of CNIs contribute to chronic allograft nephropathy and death with function--the two leading causes of late graft loss. Other recipients maintain stable graft function. METHODS: We studied the impact of continuing CNI-based immunosuppression in the second decade after kidney transplantation. From 1984 through 1996, a total of 1,263 patients underwent a primary kidney transplant at the University of Minnesota and received cyclosporine-based immunosuppression. Antibody induction was used only in deceased donor recipients. RESULTS: The actuarial 20-year patient survival rate was 38%; graft survival, 30%; and death-censored graft survival, 60%. The annual mean serum creatinine level for recipients whose grafts survived > or =1 year remained stable, although recipients with a history of > or =1 acute rejection episode had a higher serum creatinine level vs. recipients who were rejection-free. The annual mean calculated creatinine clearance was also stable over time. In addition, for recipients who were acute rejection-free, chronic allograft nephropathy/chronic rejection was only responsible for 9% of graft losses. CONCLUSIONS: Our study suggests that some kidney transplant recipients tolerate long-term CNI-based immunosuppression with stable creatinine levels. Identifying certain recipients' predisposition to CNI toxicity and individualizing immunosuppressive therapy may be important in order to improve long-term kidney function, while simultaneously preserving low short-term acute rejection rates.     

Liver transplantation for primary biliary cirrhosis: influence of primary immunosuppression on survival

INTRODUCTION: Liver transplantation is the only established curative therapy for end-stage primary biliary cirrhosis (PBC). However, the influence of primary immunosuppression on long-term patient and graft survival is still controversial. PATIENTS AND METHODS: Among 1372 patients who underwent liver transplantation from April 1989 to January 2001, 95 (6.9%) suffered from PBC. The primary immunosuppression consisted of cyclosporine (CyA; n = 56) and tacrolimus (FK; n = 39). RESULTS: The median survival of all PBC patients at 5 years was 92% and at 10 years, 90%. There was no difference between the two primary immunosuppression agents. Seven patients died, including five in the cyclosporine group (median = 25 months) and two in the tacrolimus cohort (median = 37 months). One CyA patient group died due to PBC recurrence. Seven patients underwent retransplantation without any difference in primary immunosuppression (CyA 7%; FK 10%). Fifty patients developed an acute rejection episode (CyA 57%; FK 46%); 2 patients, chronic rejection (CyA 2%; FK 4%). Fifty-five patients developed AMA titers after liver transplantation (CyA 66%; FK 46%). Patients presented cyclosporine-based regimens showed significantly (P = .001) more side effects. CONCLUSION: Long-term follow-up after liver transplantation for PBC shows excellent organ and patient survival. The choice of the primary immunsuppressant had no significant influence on patient survival, PBC-related graft loss, or development of acute or chronic rejection episodes.     

Risk factors for second renal allografts immunosuppressed with cyclosporine

Second renal allograft survival rates are lower than those of primary allografts. For recipients immunosuppressed with azathioprine, prednisone, and Minnesota ALG (conventional immunosuppression), risk factors associated with decreased second graft survival have been identified: age greater than 40, cadaver donor, less than 6 months between primary graft loss and retransplantation, duration of primary graft function (6 months or 1 year, depending on the study), high peak panel-reactive antibody, number of human leukocyte antigen mismatches, and delayed graft function. In this study, we used a multivariate analysis to identify risk factors associated with decreased second graft survival in patients who did or did not receive cyclosporine. Results were compared with primary graft survival rates. Risk factors for patients receiving conventional immunosuppression were: (a) primary graft loss caused by rejection greater than or equal to 6 months (P = 0.01 vs. either rejection less than 6 months or nonimmunologic loss); (b) cadaver donor (P = 0.005 vs. living related); and (c) interval between primary graft loss and retransplantation of greater than or equal to 6 months (P = 0.05 vs. less than 6 months). For CsA, risk factors that most decreased second graft survival were: (a) primary graft loss caused by rejection less than 6 months (P = 0.11 vs. nonimmunologic loss); (b) conventional immunosuppression for the primary graft (P = 0.08 vs. CsA immunosuppression); and (c) a peak PRA of greater than or equal to 21 (P = 0.14 vs. peak PRA of 1-20). For second graft recipients immunosuppressed with CsA, primary graft loss to either rejection greater than 6 months posttransplant or nonimmunologic causes was not a risk factor for second graft survival. These data extend the recent reports of other investigators by identifying risk factors for retransplant recipients treated with CsA and by demonstrating that subgroups of patients in the retransplant population can be retransplanted without additional risk (i.e., their second graft survival rates are similar to primary graft survival rates). This may become more important if, in the future, organ distribution is based on graft survival data. If so, our data would support retransplantation in patients who are immunosuppressed with CsA, especially those who lost their primary graft to either rejection greater than or equal to 6 months posttransplant or nonimmunologic causes; who receive living related grafts; and who have a peak PRA of 1-20.     

Risk factors for chronic rejection after pediatric liver transplantation

BACKGROUND: Chronic rejection is a major cause of graft failure and a frequent reason for retransplantation after pediatric liver transplantation. Identification of risk factors for chronic rejection in pediatric transplant recipients is vital to understanding the pathogenesis of chronic rejection and may help prevent further graft loss. METHODS: The study population consisted of 285 children with 385 liver transplants performed at University of Chicago between 1991 and 1999. Logistic regression analysis was used to evaluate risk factors for chronic rejection, including age, sex, race, type of graft (living related vs. cadaveric), native liver disease, acute rejection episodes, cytomegalovirus (CMV) infection, and posttransplant lymphoproliferative disease (PTLD). RESULTS: The chronic rejection rate was significantly lower in recipients of living-related grafts than in recipients of cadaveric grafts (4% vs. 16%, P=0.001). African-American recipients had a significantly higher rate of chronic rejection than did Caucasian recipients (26% vs. 8%, P<0.001). Numbers of acute rejection episodes, transplantation for autoimmune disease, occurrence of PTLD, and CMV infection were also significant risk factors for chronic rejection. However, recipient age, gender, donor-recipient gender mismatch, and donor-recipient ethnicity mismatch were not associated with higher incidence of chronic rejection CONCLUSION: We have identified a number of risk factors for chronic rejection in a large group of pediatric liver allograft recipients. We believe that donor-recipient matching for gender or race is not likely to reduce the incidence of chronic rejection. The elucidation of the mechanisms by which living-related liver transplantation affords protection against chronic rejection may provide insight into the immunogenetics of chronic rejection and help prevent further graft loss.