中国肝移植免疫抑制治疗与排斥反应诊疗规范(2019版)

肝脏虽为“免疫特惠器官”,肝移植术后急性排斥反应发生率及严重程度明显低于其他器官移植,但术后排斥反应仍较为常见,规范的免疫抑制治疗是保证移植效果的关键。为进一步规范肝移植术后免疫抑制治疗及排斥反应诊疗,中华医学会器官移植学分会组织肝移植专家,总结国内外相关研究最新进展,并结合国际指南和临床实践,针对肝移植术后免疫抑制剂应用原则、常用方案及各类型排斥反应的诊断与治疗,制订《中国肝移植免疫抑制治疗与排斥反应诊疗规范(2019版)》。     

中国肝移植免疫抑制治疗与排斥反应诊疗规范(2019版)

肝脏虽为"免疫特惠器官",肝移植术后急性排斥反应发生率及严重程度明显低于其他器官移植,但术后排斥反应仍较为常见,规范的免疫抑制治疗是保证移植效果的关键。为进一步规范肝移植术后免疫抑制治疗及排斥反应诊疗,中华医学会器官移植学分会组织肝移植专家,总结国内外相关研究最新进展,并结合国际指南和临床实践,针对肝移植术后免疫抑制剂应用原则、常用方案及各类型排斥反应的诊断与治疗,制订《中国肝移植免疫抑制治疗与排斥反应诊疗规范(2019版)》。     

抗体类免疫诱导剂在实体器官移植中的应用现状

器官移植是治疗终末期器官衰竭的首选有效治疗方法,然而器官移植术后早期急性排斥反应往往是导致移植失败的重要因素。为了减少器官移植后排斥反应的发生,往往需要在移植前或移植中加用强效免疫抑制剂对受体免疫系统进行抑制性诱导治疗。抗体类免疫诱导剂作为器官移植早期实施覆盖性免疫抑制治疗的常用方法,可显著减少器官移植术后早期急性排斥...     

微嵌合体诱导移植免疫耐受的研究进展

目前器官移植已经成为终末期器官功能衰竭患者的有效治疗手段,但是排斥反应仍然是器官移植术后早期功能障碍的最常见原因.通过新型免疫抑制剂的使用,可以使急性排斥反应的发生率明显下降,但同时会引起患者许多不良反应,而且免疫抑制剂对于移植慢性排斥反应和移植物的长期存活率无明显改善.     

移植免疫耐受的研究进展

器官移植是治疗终末器官功能衰竭的有效方法 ,近年来随着移植手术技术的日趋成熟、器官灌注与保存及HLA配型的不断完善、新型免疫抑制剂的开发和应用对解决移植物排斥反应、延长生存时间所起到的积极作用,促进了多种器官移植的蓬勃发展;目前虽然许多新型免疫抑制药物的应用使急性排斥反应发生率有了明显下降,但是慢性排斥反应的发生率及移植器官功能丧失并未减少,而且免疫抑制剂的长期乃至终生应用,除了经济负担之外,过度免疫抑制、病毒感染以及恶性肿瘤等也给移植病人带来了十分不利的影响.     

Toll样受体2在器官移植中的研究进展

Toll样受体(TLR)2在先天性免疫和适应性免疫中都起着重要作用,近年来,越来越多的文献报道TLR2与移植排斥反应密切相关,针对TLR2信号系统的相关免疫抑制靶点研发的免疫抑制剂可能会减轻器官移植术后的排斥反应。本文综述了TLR2在缺血-再灌注损伤、同种器官移植以及异种器官移植中的近期研究进展。     

中国肺移植免疫抑制治疗及排斥反应诊疗规范(2019版)

肺移植手术技术日臻成熟，然而急、慢性排斥反应仍严重影响肺移植受者的长期生存率。免疫抑制治疗可以减少肺移植术后排斥反应发生率，但目前免疫抑制方案尚无统一标准。为了进一步规范我国肺移植免疫抑制治疗以及排斥反应诊疗，中华医学会器官移植学分会从肺移植免疫抑制剂应用的基本原则、免疫诱导和维持治疗以及不同类型排斥反应的诊断和处理等方面，制订中国肺移植免疫抑制治疗及排斥反应诊疗规范(2019版)。     

肝移植术后严重感染状态下的严重排斥反应3例报告

回顾性分析收治的3例肝移植患者在严重感染状态下免疫抑制治疗的临床资料。结果示1例活体辅助肝移植患者几乎完全停用免疫抑制剂后发生严重排斥反应导致移植肝丧失；1例老年肝移植患者免疫抑制剂减量后出现严重排斥反应，立即予激素冲击治疗获良好效果；1例患者大幅减少免疫抑制剂后发生严重排斥反应，导致门静脉血栓形成而被迫再次肝移植。提示肝移植术后严重感染状态下行免疫抑制剂减量或停用时须密切观察是否发生急性排斥反应；一旦发生，宜果断予加强免疫抑制剂治疗。     

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。     

新的非侵入性生物标志物microRNA在器官移植中的应用研究

外科技术和免疫抑制治疗的发展已经显著改善器官移植患者术后的近期生存率。然而,仍有诸多因素影响患者的长期预后,如免疫抑制剂的不良反应、原发病复发、感染、急性与慢性排斥反应、新发恶性肿瘤及代谢性疾病等,而这些影响移植物和患者长期存活的不利因素都直接或间接与免疫抑制剂有关。因此,准确评价移植患者的免疫状态尤为     

Incidence of Renal and Liver Rejection and Patient Survival Rate Following Combined Liver and Kidney Transplantation

Multiple organ transplantations are used to treat chronic multiple organ failure. However, long-term mortality and graft tolerance remain to be evaluated. We carried out a retrospective and comparative analysis of 45 patients who underwent a combined liver and kidney (LK) transplantation (LKT) from the same donor. They were compared to 86 matched patients who underwent kidney (K) transplantation (KT). All patients had an organic renal failure associated with cirrhosis (n = 35) or with inherited disease (n = 10). Nineteen (42.9%) had been transplanted previously. The patients' survival rate was 85% at 1 year and 82% at 3 years. Seven patients died within the first 3 months, due to severe polymicrobial infection. Two patients in the LK population (4.2%) developed acute rejection of the kidney graft compared to 24 of the 86 matched renal transplanted patients (32.6%). In parallel, acute liver rejection was observed in 14 cases (31.1%) in the LK population. The occurrence of acute rejection was not associated with panel-reactive lymphocytotoxic antibodies (n = 16), nor with positive cross-matches (n = 3). Four of the 45 patients (8.8%) subsequently developed chronic renal allograft rejection, and 16 cases of chronic hepatic dysfunction were noted (42.2%). In conclusion, the overall survival rate following combined liver kidney transplantation is acceptable, and LKT can be proposed to patients with kidney failure associated with liver dysfunction, primary oxaluria or amyloid neuropathy. The main cause of mortality in this population was severe infectious complications. The frequency of acute kidney rejection was lower than in single transplantation.     

Lung transplants with tacrolimus and mycophenolate mofetil: a review

Traditionally, immunosuppressive maintenance therapy in solid organ transplantation has consisted of cyclosporine (CsA), azathioprine, and prednisone. However, lung transplant recipients are far more frequently affected by acute rejection, especially during the first 6 months after the transplantation, than patients with other transplanted organs. Further, they display a greater risk for chronic transplant dysfunction and ultimate graft loss. Bronchiolitis obliterans syndrome (BOS) is the major cause of morbidity and mortality among long-term survivors after lung transplantation. Acute pulmonary allograft rejection has been identified as the major risk factor for the development of BOS. Based on favourable results in kidney, liver, and heart transplantation, tacrolimus and mycophenolate mofetil have been used as primary prophylaxis and as rescue therapy for recurrent or persistent acute rejection and BOS. A secondary indication is CsA toxicity. This review focuses on reported results of the combination of tacrolimus and mycophenolate mofetil in lung transplantation. These new immunosuppressive drugs have markedly improved the efficacy profiles without additional detrimental toxicities, and appear to be a safe alternative to CsA and azathioprine in patients following lung transplantation. However, at present, BOS is not influenced by these new drugs. The optimal long-term immunosuppressive regimen remains to be established.     

Controversies in combined liver-kidney transplantation: indications and outcomes

Controversy surrounds simultaneous transplantation of a kidney and a liver because the practice is increasing, and organs for transplant are limited. Not only do recipients of both organs use 2 rather than 1 organ, but the kidney in dual transplantation jumps to the front of a very long kidney wait-list. Furthermore, there is suspicion that some patients who undergo combined liver and kidney transplantation may have reversible renal failure. Likewise, inappropriate liver transplantation in those with end-stage renal disease is possible given the heavy weighting of kidney dysfunction in the calculation of the model for end-stage liver disease score. Thus, a better way to determine the recoverability of renal dysfunction in liver transplant candidates and the degree of liver disease in end-stage renal disease is needed. Standardized strategies for candidate evaluation, selection, and process review are also necessary to improve organ allocation in those with both liver and kidney disease. However, basic and clinical investigation will be needed before an optimal algorithm is possible.     

Kombinierte Nieren-Pankreas-Transplantation

BACKGROUND: Differences in graft survival due to gender have been reported after transplantation of the kidney, liver, and heart. However, little is known about the role of donor and recipient gender in simultaneous pancreas-kidney transplantation. METHODS: Single-centre analysis was performed of first simultaneous pancreas-kidney transplantations performed between 1994 and 2005 at the Bochum Transplant Center in Germany (n=218). RESULTS: Recipients of female donor organs exhibited acute organ rejections earlier and more frequently (P<0.05). Male recipients of organs from male donors had a lower risk of acute rejection than recipients of female donor organs (P<0.05). In addition to female donor gender, higher donor age and early kidney dysfunction were risk factors for perioperative rejection (P<0.05). Long-term kidney and pancreas function was best in male-donor-to-female-recipient transplants over the time periods of 7 and 3 years, respectively (P<0.05). Risk factors of long-term organ failure were: the need of revision laparotomy, organ rejection, and early postoperative organ dysfunction (P<0.05). CONCLUSION: This is the first report of graft function after simultaneous pancreas-kidney transplantation looking specifically at gender differences with respect to donor and recipient. There was an increased risk of organ rejection of female donor organs.     

Mycophenolate mofetil added to immunosuppression after liver transplantation – first results

Mycophenolate mofetil (MMF) has been used successfully as an immunosuppressive agent after kidney and heart transplantation, but experience with MMF after liver transplantation is still limited. Between August 1995 and January 1996, we treated 20 patients with MMF after orthotopic liver transplantation in an open, prospective study. Five out of eight patients with acute rejection and one patient with early chronic rejection showed a complete response after MMF was added to the immunosuppression. Three patients with chronic rejection did not improve, one died, and two have stable graft function at present. In eight patients who suffered from toxicity, a reduction in the dosage of tacrolimus was attempted with simultaneous MMF therapy. One patient died due to multiple organ failure. Liver function improved completely in one other patient, and partially in three patients after adding MMF. In the remaining three patients, a reduced dosage of tacrolimus or cyclosporin, together with MMF, reduced toxicity, not significantly. In conclusion, MMF appears to be a safe and potentially useful adjuvant immunosuppressive agent for rescue and maintenance therapy. Received: 15 August 1996 Accepted: 6 December 1996     

What do we know about the clinical impact of complete withdrawal of immunosuppression in liver transplantation?

The liver is a privileged organ with a lower incidence of rejection than other organs. However, immunosuppressive regimens are still required to control the alloreactive T-lymphocyte response after transplantation. These treatments may lead to severe complications, such as infectious diseases, cancers, cardiovascular diseases, and chronic renal insufficiency. In clinical transplantation, there is increasing evidence that some liver transplant recipients who cease taking immunosuppressive drugs maintain allograft function, suggesting that tolerance is already present. This strategy is feasible in 25% to 33% of liver transplant recipients. Few of the studies performed so far have provided a detailed analysis of the impact of immunosuppression (IS) withdrawal on pre-existing complications derived from the long-term administration of immunosuppressive drugs and the side effects associated with it. In preliminary studies, IS withdrawal was safely achieved in selected liver transplant patients, and improved not only kidney function, but also other IS-associated side-effects such as hypercholesterolemia, hyperuricemia, hypertension, and diabetes control. However, longer follow-up periods are needed to confirm the benefits of IS withdrawal in liver transplant patients.     

肝肾联合移植治疗巨大多囊肾合并多囊肝并发肝肾功能衰竭

目的 总结巨大多囊肾合并多囊肝并发肝肾功能衰竭行肝肾联合移植的临床经验.方法 对8例巨大多囊肾合并多囊肝并发肝肾功能衰竭的患者进行肝肾联合移植,男性5例,女性3例;年龄41～67岁,平均52.8岁.先肝后肾采用经典非转流原位肝移植6例,先肾后肝并采用背驮式肝移植2例.术后对急性排斥反应、并发症、肝肾功能、人/肝/肾存活率等临床疗效进行长期随访.结果 随访28～65个月,8例患者均存活,肝肾功能正常.存活5年以上2例,4年以上2例,2年以上4例.围手术期并发胸腔积液2例,肺部金黄色葡萄球菌感染1例,均对症治疗后痊愈.截至随访终点,未发现移植物急性排斥反应.结论 巨大多囊肾合并多囊肝并发肝肾功能衰竭的患者,肝肾联合移植术是安全有效的治疗方法.     

肝肾联合移植治疗巨大多囊肾合并多囊肝并发肝肾功能衰竭

目的 总结巨大多囊肾合并多囊肝并发肝肾功能衰竭行肝肾联合移植的临床经验.方法 对8例巨大多囊肾合并多囊肝并发肝肾功能衰竭的患者进行肝肾联合移植,男性5例,女性3例;年龄41～67岁,平均52.8岁.先肝后肾采用经典非转流原位肝移植6例,先肾后肝并采用背驮式肝移植2例.术后对急性排斥反应、并发症、肝肾功能、人/肝/肾存活率等临床疗效进行长期随访.结果 随访28～65个月,8例患者均存活,肝肾功能正常.存活5年以上2例,4年以上2例,2年以上4例.围手术期并发胸腔积液2例,肺部金黄色葡萄球菌感染1例,均对症治疗后痊愈.截至随访终点,未发现移植物急性排斥反应.结论 巨大多囊肾合并多囊肝并发肝肾功能衰竭的患者,肝肾联合移植术是安全有效的治疗方法.     

肝肾联合移植二例报告

目的 探讨肝肾联合移植的手术技术、治疗经验及疗效。方法 给２例肝炎后肝硬变、肝功能不全合并慢性肾功能衰竭患者施行一期肝联合移植。供体器官采用ＵＷ液原位灌洗,快速联合切取。肝移植采用原位肝移植技术,肾移植采用常规方法。术后免疫抑制治疗采用环孢素Ａ霉酚酸酯、抗淋巴细胞球蛋白和激素联合应用。分别于手术５０ｄ与４０ｄ开始服用抗乙型肝炎病毒药物拉米呋啶。结果 例１移植器官立即发挥功能,术后１１０ｄ移植肾发生