他克莫司撤药诱发大鼠肝移植急性排斥反应的病理学观察与分析

目的建立大鼠肝移植急性排斥反应动物模型,观察大鼠肝移植术后他克莫司撤药诱发受体急性排斥反应的肝脏动态病理学变化,为临床肝移植术后他克莫司停药或者用药不规律所致急性排斥反应的预测和评估提供理论依据。方法通过Kamada二袖套法,建立雄性DA大鼠至Lewis大鼠的原位肝移植模型60例。受体大鼠术前1 d和术后7 d内饲喂治疗剂量的他克莫司,之后半量递减至停药。分别于术后7、14、21及28 d处死部分受体大鼠,获取肝组织标本,观察受体大鼠肝脏大体和镜下的动态病理学改变,并进行排斥活动指数评分,同时观察受体大鼠的术后生存时间。结果受体大鼠术后7 d内由于受他克莫司的保护,肝脏未出现典型的急性排斥反应表现,至术后14 d由于他克莫司的减量及撤出,迅速发生肝脏的急性排斥反应,术后14、21及28 d排斥活动指数评分分别为(3.7±0.9)分(、6.3±0.9)分和(8.1±0.7)分。受体术后生存时间为(20.85±0.71)d,中位生存期为21 d。结论通过围手术期短期饲喂治疗剂量他克莫司并逐渐减量至撤药诱发肝移植大鼠急性排斥反应模型术后的急性排斥反应,动态观察该实验条件下排斥反应发生的时限和严重程度,对临床肝移植术后类似情况下所发生的急性排斥反应具有一定的预测价值和严重程度评估价值。     

成人-成人活体右半肝移植16例报告

目的　报道东京大学 16例成人终末期肝病患者进行活体右半肝移植的经验。方法　统计自 2 0 0 0年 10月到 2 0 0 1年 4月 ,对 16例成人终末期肝病患者进行了活体右半肝移植。供体和受体的平均体重分别为 5 5kg(42 - 78kg)和 5 7kg(41- 81kg)。结果　供体手术的平均失血量为 80 0ml(30 0 - 16 0 0ml) ,供体的平均住院时间为 12d(6 - 38d)。 14例供体未输血。 1例供体术后发生并发症。移植肝的平均重量为 719g(45 0 - 10 5 0g) ,所有移植肝均立即恢复功能 ,病人精神状态康复 ,凝血酶原时间恢复正常。 2例受体需要再次手术探查。 2例患者死亡 (1例在术后 16d死于全身性念珠菌感染 ,另 1例在术后 2 6d死于门静脉栓塞 )。结论　认为采用右半肝的活体肝移植可以提供足够体积和功能的肝脏达到较好的结果 ,为成年患者的肝移植提供了新的选择     

成人间右半肝活体肝移植肝中静脉的处理

目的 总结成人间右半肝活体肝移植肝中静脉的处理经验。方法 回顾性分析两例成人间右半肝活体肝移植肝中静脉的处理方法，1例采取含肝中静脉的右半肝活体肝移植，肝中静脉移植供肝和剩余肝脏各保留一半，既有利于保证供体左肝内叶静脉回流，同时供肝右前叶静脉回流也不受到影响；另1例则采取不含肝中静脉的右半肝活体肝移植，术中重建供肝右前叶肝静脉回流通道，使供肝前叶淤血明显改善。结果 两例供体均存活，术后顺利出院，无并发症；受体1例存活，1例术后20d死于急性重度排斥反应。结论 成人间右半肝活体肝移植肝中静脉的处理十分关键，要注意保持供受体肝流出道的通畅，既要保证供体的绝对安全，又要尽量为受体提供足够的肝容量。     

MHC-Ⅱ类分子反式激活因子基因沉默对大鼠肝移植急性排斥反应的抑制作用

组织化学检测MHC-Ⅱ抗原表达水平,其余受体观察生存期.结果 NS组、对照组和shRNA组大鼠肝移植术后平均生存期分别为7.75、7.25和15.75 d,shRNA组大鼠生存期明显延长(P＜0.01);shRNA组大鼠的排斥反应病理分级明显减低(P＜0.01),CⅡTA和MHC-Ⅱ的mRNA表达水平及MHC-Ⅱ抗原表达水平均显著降低(P＜0.01).结论 沉默供体肝脏CⅡTA基因表达可以有效减轻大鼠肝移植急性排斥反应,其机制可能与干预免疫识别有关.     

TGF-β1与大鼠肝移植免疫耐受的关系

在大鼠不同品系间行肝移植,某些品系的移植肝可以被受体自发性免疫耐受。例如将BN大鼠的肝脏移植到Lewis大鼠中可以发生自发性免疫耐受,但是反过来却发生急性排斥反应。在肝移植的实践中,由于供体的缺乏,促进了劈肝移植(splittingliver transplantation)和活体肝移植(living livertransplantation)的迅速发展。在这两种术式中,均可能发生移植肝与受体体重之比小于正常,该移植物称为“小体积移植物”(small for size)。移植后的     

肝移植术后巨细胞病毒再感染的预防与治疗

目的　探讨肝移植术后巨细胞病毒(CMV)再感染的预防、诊断及治疗。方法　回顾性分析44例原位肝移植患者的临床资料。结果　44 例中,术前43 例(97.7 %)有CMV潜伏性感染,其中6例(14.0 %)术后发生CMV再感染。6例CMV再感染患者的CMV pp65抗原均为阳性,3例CMV IgM阳性,均为无临床症状的CMV活动性感染,其中5例治愈,无一例发展为CMV病,1 例因上消化道大出血死亡。43例中,仅有7例CMV再感染高危病例接受了抗CMV感染的预防性治疗,患者在生存期内未发生CMV再感染。结论　在我国,肝移植患者术前CMV潜伏性感染的发生率较高,测定CMV pp65抗原可以早期诊断CMV再感染;对CMV再感染的高危患者进行预防性治疗可以降低术后CMV再感染的发生率;对无临床症状的CMV再感染者进行及时、规范的治疗是防止CMV病发生的关键。     

活体肝移植供体的选择及术后评估28例

目的探讨活体肝移植供体的选择标准 ,评估其术后状况。方法回顾总结 1995年1月至 2 0 0 3年 7月 2 8例活体肝移植供体术前检查、选择标准 ;术后随访其肝肾等重要脏器功能、并发症情况。结果 2 8例供体平均住院日为 10 (8～ 2 0 )d。本组 1例术后发生肝脏断面渗血 ,经保守治疗后痊愈。 1例在“T”形管拔除后发生胆漏 ,经手术引流后痊愈。其余 2 6例无并发症出现。随访时间 2个月至 8年。所有供体均恢复正常体力活动。结论保证供体的安全是开展活体肝移植的首要原则。在具备丰富肝脏手术经验的基础上 ,供体手术是安全、可行的。     

肝移植多模式策略的初步探讨

目的：总结多种临床肝移植技术的经验。方法：对2000年9月至2002年3月完成的25例临床肝移植（27次移植手术）的资料进行回顾性分析。包括尸肝移植14例,活体肝移植11例,再次尸肝移植1次,减体积再次肝移植1次。结果：11例活体肝移植的供体中,10例为患者之母亲,1例急诊成人右叶活体肝移植供体为患者之妹。供肝方式：扩大左半肝6例,右半肝3例,右半肝2例;切取供肝重量270－620g。全组存活24例,1例成人活体肝移植受体于术后72d死于不可逆转的严重排斥反应。肝炎患者采用拉米呋啶加抗HVB－Ig治疗,10例乙肝、肝硬化患者术后随访时间4－21个月,复查HVB－DNA均为阴性。所有肝豆状核变性受体术后随访复查6－17个月,铜氧化酶、肝功能均正常。本组主要并发症包括：腹腔出血2例,需再次剖腹探查止血;ARDS 5例;急性肾功能衰竭2例;排斥反应4例,其中1例导致死亡。结论：综合开展包括尸体肝移植、活体肝移植、减体积肝移植等在内的各项技术,充分利用有限的供肝,是优化肝移植资源,提高移植疗效的重要途径。     

活体肝移植的几点关键外科技术

目的：探讨活体肝移植的几点关键外科技术。方法：2001年1月至2002年3月底,实施活体肝移植11例,其中左半肝8例,左外叶1例,成人右半肝2例;根据术前CT、血管造影和术中B超确定肝切除线,超声电刀离断肝实质,经门静脉灌注原位获取。受体手术采用保留腔静脉的全肝切除。移植肝原位植入,肝静脉重建采用扩大成型吻合技术,显微技术吻合肝动脉,胆道重建采用端端吻合,置“T“管引流。结果：11例供体术后顺利康复出院,未发生严重并发症。11例受体中,1例发生肝动脉血栓形成需再次肝移植,1例因不可逆转的严重排斥反应,于术后72d死亡。10例受体康复出院,肝功能、铜氧化酶恢复正常。结论：活体肝移植对供体是相对安全的。管道重建技术是活体肝移植的重要环节。术前、术中了解供体的解剖变异并正确处理,可降低并发症发生率。     

肝脏移植治疗肝癌八例

目的　探讨肝脏移植治疗原发性肝癌的可行性。　方法　从 1995年 7月至 1998年 10月 ,玛丽医院共为 8例伴有肝硬化的肝癌患者行肝移植术。其中活体肝移植 2例 ,尸体肝移植 6例。5例术前已诊断为肝癌 ,3例为意外发现的肝癌。除 1例术前曾行抗癌治疗外 ,其余患者手术前后均未行任何抗癌治疗。TNM分期 :Ⅱ期 5例 ,Ⅲ期 2例 ,Ⅳa期 1例。术后患者平均随访 36个月。　结果　 3例术后发生急性排斥反应 ,5例术后早期有并发症发生 ,均得到及时处理并缓解。 1例术后 1年死于败血症。术后 1年生存 8例 ,3年生存 7例。　结论　肝移植治疗肝癌是可行的。活体亲属肝移植可缓解供体短缺的矛盾及避免患者在等候肝移植期间病情恶化。     

Comparison of serology assays and polymerase chain reaction for the monitoring of active cytomegalovirus infection in renal transplant recipients

BACKGROUND: Cytomegalovirus (CMV) infection is a common complication of renal transplantation. It can be diagnosed serologically, mainly based on seroconversion or by the detection of viral antigen via CMV-DNA amplification (polymerase chain reaction [PCR]). AIM: We sought diagnosis of an active CMV infection in renal transplant patients comparing serologic assays of CMV-IgM antibodies with CMV-DNA amplification. METHODS: We retrospectively studied renal transplant recipients 26 (including 15 women) hospitalized with clinical suspicion of CMV disease. The diagnosis of CMV infection was suspected on the basis of nonspecific symptoms, including fever, leukopenia, hyperbilirubinemia, and alanine aminotransferase elevation, alone or in combination. At the time of admission, all patients were screened for CMV-IgM antibody (immunoassays AxSYM/IMx) and CMV-DNA (qualitative PCR). RESULTS: The confirmation of CMV infection by the two methods (immunoassay and PCR) was obtained in only three patients (11.5%), its unambiguous exclusion--in four cases (15.4%). Nineteen patients (73.1%) were positive for CMV-IgM and negative for CMV-DNA. CONCLUSION: Detection of CMV-IgM antibodies by various immunoassays is not sensitive enough for diagnosis and cannot be used for monitoring during the active period in renal transplant recipients. This observation supported the prolonged presence of IgM antibodies after recent CMV infection in this patient group.     

Deferred versus prophylactic therapy with gancyclovir for cytomegalovirus in allograft liver transplantation

OBJECTIVE: The aim of this study was to assess the efficacy of deferred versus prophylactic therapy with gancyclovir to prevent cytomegalovirus (CMV) infection or disease in liver transplantation recipients, and to alter the timing of infection or the incidences of acute rejection, chronic rejection, or death. METHODS: We retrospectively studied 89 consecutive liver transplant recipients with a minimum of 1 year follow-up. CMV early antigen detection (pp65) was performed weekly for the first 2 months and thereafter monthly for an additional 10 months. Forty-one recipients were administered prophylactic treatment and (48 recipients) deferred therapy for positive antigenemia. RESULTS: During the first year after transplantation, CMV infection or disease developed in 61% or 12.2% of those treated with prophylactic therapy and 54.1% or 31.3% of those treated with deferred therapy (P = 0.51 or P = 0.032, respectively). The mean time to CMV disease in the prophylactic group was 161 +/- 33 days compared with 82 +/- 27 days for the deferred therapy arm (P < 0.001). Subgroup analysis based on CMV serological status also showed prophylactic treatment significantly diminished CMV disease in the CMV IgG antibody negative group. No patients died in the prophylactic group, and one died in the deferred group (P = 0.54). The incidence of acute rejection episodes was 34% in the prophylactic and 46% in the deferred group (P = 0.26). Chronic rejection was observed in two recipients in the prophylactic group versus one recipient in the deferred arm (P = 0.35). CONCLUSION: Compared with deferred therapy prophylactic therapy with gancyclovir decreased CMV disease and delayed the onset of CMV disease after liver transplantation.     

肝移植病人术后巨细胞病毒感染的预防和治疗

目的 分析肝移植术后病人巨细胞病毒(CMV)感染的诊断、预防和治疗。方法 采用回顾性分析的方法，分析我科2000年8月至2002年1月期间进行的同种异体原位肝移植病例。结果 共进行同种异体原位肝移植36例。术后8例发生巨细胞病毒感染，其中2例出现腹泻，发热2例，1例为黄疸，4例无明显症状。在CMV感染的病人中，检测到CMV—IgM( )或(和)CMV-DNA( )，其中CMV—IgM( )5例，CMV-DNA( )6例。病人经更昔洛韦治疗后血清CMV-DNA变为阴性。全部治愈。结论 对病人CMV—IgM和CMV—DNA(FQ-PCR方法)联合检测应用能够对CMV感染病人作出诊断并且指导治疗。更昔洛韦能够有效的治疗CMV感染。     

肾移植术后的巨细胞病毒感染及其对急性排斥反应的影响

目的 探讨肾移植受者术后活动性巨细胞病毒（ＣＭＶ）感染的发生率、感染的原因以及ＣＭＶ感染对急性排斥反应的影响。方法 检测１８７例肾移植受者和供者术前血清抗－ＣＭＶ抗体;受者术后定期检测体内ＣＭＶ ＤＮＡ、对ＣＭＶ ＤＮＡ阳性的部分患者给予抗ＣＭＶ治疗,并比较各组排斥反应的发生率。结果 无论是供者还是受者,术前如血清抗－ＣＭＶ抗体阳性,受者术后发生活动性ＣＭＶ感染者明显增多,这些患者急性排斥反应的发     

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.     

HLA-G与肾移植术后急性排斥反应和巨细胞病毒活动性感染的相关性研究

目的 探讨HLA-G的表达水平与肾移植术后急性排斥反应(AR)和巨细胞病毒(CMV)活动性感染的相关性.方法 根据术后是否发生AR或CMV活动性感染,将132例初次肾移植受者分为肾功能稳定组、AR组和CMV组.另选择41例健康供者作为对照组.采用流式细胞术、酶联免疫吸附试验、蛋白质印迹法以及实时定量聚合酶链法检测各组HLA-G及其mRNA的表达,并采用免疫组织化学法观察移植肾组织中HLA-G的表达.结果 肾移植前后各组膜结合型HLA-G1 (mHLA-G1)的表达均处于较低水平,仅术后CMV组mHLA-G1+的中性粒细胞出现显著升高(P＜0.05).术前可溶性HLA-G5(sHLA-G5)的表达水平肾功能稳定组显著高于对照组(P＜0.05);术后sHLA-G5的表达水平CMV组显著高于肾功能稳定组(P＜0.05),而肾功能稳定组均高于对照组和AR组(P＜0.05),AR组与对照组的差异无统计学意义(P＞0.05).术后CMV组sHLA-G5 mRNA的表达水平最高(P＜0.05),肾功能稳定组次之,对照组和AR组均较低.21例AR组移植肾组织活检样本中,17例HLA-G表达呈阴性,3例呈阳性,1例呈弱阳性;9例CMV组移植肾组织活检样本的HLA-G表达均为阳性.132例受者中,28例CMV感染者的AR发生率为7.1％(2/28),104例非CMV感染者的AR发生率为25.0％(26/104),二者间AR发生率的差异有统计学意义(P＜0.05).结论 sHLA-G5可作为预测AR和CMV感染的生物标志分子;CMV感染和AR与受者体内的免疫平衡状况相关.     

Risk Factors of Cytomegalovirus Infection After Pediatric Liver Transplantation

PurposeCytomegalovirus (CMV) infection is known to be the most frequently viral infection among patients after liver transplantation. This is especially true in pediatric living-donor liver transplantation because the recipients have often not been infected with CMV and postoperative primary infection with CMV frequently occurs.Patients and MethodsOf 93 patients who underwent pediatric liver transplantation at our department, 33 patients (36.3%) were diagnosed with CMV infection using the antigenemia method (C7-HRP). Retrospective review and statistical analysis were conducted to confirm risk factors of post-transplantation CMV infection.ResultPositive lymphocytes were diagnosed between postoperative days 8 and 111 after transplantation. Ganciclovir or foscavir were administrated to 21 patients. The other 10 patients who had one positive lymphocyte were observed and the cell disappeared on follow-up examination. We did not observe any cases of positive lymphocytes with C7-HRP in patients who received a graft from a CMV antibody?negative donor. Independent predictors associated with CMV infection in the multivariable analysis were administration of OKT3 and grafts from CMV antibody?positive donors.ConclusionIn CMV infection after pediatric liver transplantation, cases with CMV antibody?positive donors and with OKT3 administration for acute rejection are considered high risk, and cases with CMV antibody?negative donors are considered low risk.     

Infectious complications in kidney transplant recipients: a single-center experience

To determine the patterns of infectious complications in renal transplant recipients in our center, we evaluated 48 patients (29 men and 19 women) who were transplanted between 1994 and 2003. The average age of the patients was 29 years. Thirty (62.5%) and 18 (37.5%) transplants were from living related and cadaveric donors, respectively. Posttransplant immunosuppression consisted of azathioprine or mycophenolate mofetil (MMF), prednisone, antithymocyte globulin (ATG), and cyclosporine or tacrolimus. The acute rejection episodes were treated with pulse doses of methylprednisolone; steroid-resistant rejection was treated with ATG or muromonab (OKT3). All patients received prophylaxis with sulfadoxine-pyrimethamine; none received prophylaxis against cytomegalovirus (CMV) infection. Thirty-nine (81%) recipients developed 77 confirmed episodes of infection; 35 (46%) episodes occurred in the early postoperative period, 28 (36%) in the first month and 14 (18%) after 6 months. According to the type of infection, there were 24 urinary tract, 16 CMV, seven herpetic, nine general septic, six fungal, four pneumonia, one disseminated nocardial, and 10 miscellaneous episodes. All 26 (100%) patients who had acute rejection episodes developed infections compared with 13/22 (59%) who did not have rejection (P < .01). There was a significant correlation between CMV disease and acute rejection and/or tacrolimus or MMF use. CMV infection occurred after the additional immunosuppressive treatment for acute rejection in 10 patients or during the use of tacrolimus or MMF in six patients. We conclude that CMV infection was the most frequent opportunistic pathogen in our renal transplant population and related to the intensive antirejection therapy, followed by urinary tract infections within 3 months after surgery.     

Cytomegalovirus as a risk factor in living-related renal transplantation. A prospective study.

Forty-four living-related donor kidney (LRD) recipients (19 HLA-identical and 25 haploidentical) were followed prospectively to determine the posttransplant incidence and sequelae of cytomegalovirus (CMV) infection as they relate to the CMV status of recipients and donors. CMV titers were measured in all patients before transplantation by an immunofluorescent assay (IFA). Recipients similarly had CMV titers measured at selected intervals after transplant and during febrile episodes. Appropriate viral cultures were simultaneously performed. Laboratory evidence of infection was correlated with symptoms and signs of active CMV disease. Mean follow-up period was 20 +/- 12 months with a range of 3-51 months. Three patients were excluded due to early acute rejection resulting in graft loss. Twenty-eight of 41 donors (68%) and 22 of 41 recipients (54%) had positive CMV titers before transplantation. Six of 41 recipients (15%) subsequently developed clinical and laboratory evidence of CMV infection: three of 19 seronegative recipients and three of 22 seropositive recipients. All six patients received kidneys from seropositive donors. Four patients had severe CMV disease (2 seronegative, 2 seropositive), whereas two patients had leukopenia and fever only. Two patients with severe CMV infections subsequently lost their grafts due to unrelated causes. Overall, actual patient and graft survival of the entire group is 95% and 82%, respectively. In conclusion, individuals who receive LRD kidneys from seronegative individuals are unlikely to develop CMV infection, and transplantation of seropositive LRD kidneys may be associated with transmission of CMV in susceptible recipients regardless of their serologic status. With appropriate management of CMV illness in the posttransplant period, LRD kidney donation is safe and efficacious and should not be discouraged on the basis of pretransplant CMV serology in any donor-recipient pairing.     

The Impact of Cytomegalovirus Infection and Disease on Rejection Episodes in Renal Allograft Recipients

Cytomegalovirus (CMV) infection and disease are potential risk factors for acute allograft rejection in renal transplant recipients. The present study specifically addresses this issue. From October 1994 to July 1997, 477 consecutive renal allograft recipients (397 first transplants and 80 retransplants) were included in the study. CMV infection (cytomegalovirus pp65 antigen in leukocytes) and disease (infection and clinical symptoms or signs of disease) were examined prospectively for 3 months. No CMV prophylaxis was given, and CMV disease was treated with intravenous (i.v.) ganciclovir. The retransplantation of four patients transplanted twice during the study and 22 patients receiving kidneys from human leucocyte antigen (HLA)-identical siblings were excluded from statistical analysis. Rejections were evaluated clinically [277(61%)] and 173 (38%) also had a biopsy verified rejection. CMV infection occurred in 64% of the patients and 24% experienced CMV disease. In a multiple time-dependent Cox analysis, CMV infection and CMV disease were independent significant predictors for clinical acute rejections, RR = 1.6 (1.1-2.5, p = 0.02) and RR = 2.5 (1.2-5.1, p = 0.01), respectively. Among 173 patients with biopsy verified rejection, 72% of the patients had tubulointerstitial rejection whereas 28% had a vascular rejection. CMV disease, but not CMV infection was a predictor of tubulointerstitial rejection, RR = 3.1 (1.1-9.3, p = 0.04). CMV infection and disease are independent risk factors for clinical acute rejection in kidney allograft recipients. CMV disease is an independent risk factor for biopsy verified acute tubulointerstitial rejection in kidney allograft recipients.