Development of the allocation system for deceased donor liver transplantation

As the number of pre- and post-transplant solid organ recipients continues to grow, it becomes important for all physicians to have an understanding of the process of organ procurement and allocation. In the United States, the current system for allocation and transplantation of human solid organs has been heavily influenced by the experience in deceased donor liver transplantation (DDLT). This review highlights the significant changes that have occurred over the past 10 years in DDLT, with specific attention to the impact of the Model for Endstage Liver Disease (MELD) score on organ allocation and pre- and post-transplant survival. DDLT is managed by the United Network for Organ Sharing (UNOS) which oversees organ procurement and allocation across geographically defined Organ Procurement Organizations (OPOs). For many years, deceased donor livers were allocated to waiting list patients based on subjective parameters of disease severity and accrued waiting time. In addition, organs have traditionally been retained within the OPO where they are procured contributing to geographic disparities in disease severity at the time of transplantation among deceased donor recipients. In response to a perceived unfairness in organ allocation, Congress issued its "Final Rule" in 1998. The Rule called for a more objective ranking of waiting list patients and more parity in disease severity among transplant recipients across OPOs. To date, little progress has been made in eliminating geographic inequities. Patients in the smallest OPOs continue to receive liver transplants at a lower level of disease severity. However, strides have been made to standardize assessments of disease severity and better prioritize waiting list patients. The MELD score has emerged as an excellent predictor of short-term mortality in patients with advanced liver disease, and patients listed for liver transplantation are now ranked based on their respective MELD scores. This has improved organ access to the most severely ill patients without compromising waiting list mortality or post-transplant survival. The current system for DDLT remains imperfect but has improved significantly in the past decade. As the number of patients in need of DDLT grows, the system will continue to evolve to meet this increasing demand.     

Organs shortage in the United States

Since the law pertaining to deceased transplantation was legalized in October 1997 in Japan, 140 cases of deceased transplants have been performed through March 2005. Patients on waiting lists, however, are increasing every year. Meanwhile patients traveling abroad in desperations to require donors also increase. In the United States, over 25,000 transplantations are performed annually. The number of patients on waiting list exceeded 86,000 in 2003. Organ shortages are a serious problem, even in the United States. Expanded criteria donor(ECD) and Model for endstage liver disease (MELD) scoring systems were implemented to improve some problems in kidney and liver allocation systems, respectively in 2002. Utilization of donated organs for non-citizens is limited in the United States. Japan must independently increase deceased donor transplantations.     

Liver transplantation--present and future

The outcome of liver transplantation for HBV-related liver disease has been dramatically improved by the introduction of hepatitis B immune globulin and antiviral drug such as lamivudine. On the other hand, prophylaxis against HCV recurrence has not been established. As for hepatocellular carcinoma, Milan criteria predict acceptable posttransplant outcome. MELD scores, calculated from serum creatinine, bilirubin, and PT-INR, have been shown to be effective in predicting patient survival 1) on the waiting list and 2) following transplantation. ABO-incompatible liver transplantation has been associated with poor patient survival, especially when the recipients are adults. Intraportal infusion of methylprednisolone, prostaglandin E1, and gabexate mesilate, however, has been reported to be effective. It has been reported that 12.4% of the living liver donor experienced postoperative complication, and therefore, more effort should be made to increase brain-dead donor.     

Complications of orthotopic liver transplantation: imaging findings

Orthotopic liver transplantation has become the major treatment for end-stage chronic liver disease and for severe acute liver failure. Despite the improvement in survival due to advances in organ preservation, improved immunosuppressive therapy agents, and refinement of surgical techniques, there are significant complications after liver transplantation. These complications mainly include biliary strictures, stones, and leakage; arterial and venous stenoses and thromboses; lymphoproliferative disorders; recurrent tumors; hepatitis virus C infection; liver abscesses; right adrenal gland hemorrhage; fluid collections; and hematomas. The diagnosis of acute rejection, one of the most serious complications after liver transplantation, is established with graft biopsy and histologic study. The role of imaging methods consists of excluding the other complications, which can have clinical signs and symptoms similar to those of acute rejection. This pictorial essay describes imaging findings of the various complications after liver transplantation and focuses on their radiologic diagnosis. Knowledge and early recognition of these complications with the most suitable imaging modality are crucial for graft and patient survival.     

Organ donation in Switzerland

Since 1985 Swisstransplant coordinates all allocations for organ transplantations in Switzerland. During these 20 years the number of deceased donors decreased, while the number of living donors increased. In the same period the number of patients on a waiting list for organ transplantation increased significantly, up to more than 1000 at the end of2004. During the year 2004 412 patients were transplanted, 43 (4%) died while waiting on the list. In comparison to other European countries the frequency of organ donation from deceased donors is relatively low in Switzerland, only 13 per million inhabitants. In order to treat the high number of patients needing organ transplantation, additional efforts have to be undertaken in future. The measures include the development of alternative therapies preventing or treating organ failure, the amelioration of legal conditions of organ transplantation with the new law, an increase of resources and knowledge to improve donor evaluation and donor pools in the donor hospitals, a further improvement of the allocation process, the enhancement of information and motivation of the population by the patient organisations, the medical staff, Swisstransplant and eventually public means.     

人工肝支持系统对高危患者肝移植术后生存率的影响

目的 观察重型肝炎肝移植术前进行人工肝支持系统(ALSS)治疗对术后生存率的影响.方法 将符合重型肝炎诊断标准且术前终末期肝病模型(MELD)评分＞35分的患者根据移植术前是否行ALSS治疗分成试验组(23例)和对照组(41例).两组患者分别在进入肝移植等待名单时和术前1 d进行全身情况评估,术后定期随访,使用Kaplan-Meier进行生存情况分析,用Log-Rank检验比较两组患者生存率的曲线.结果 两组患者在进入肝移植等待名单时凝血酶原时间、纤维蛋白原、总胆红素、血氨、肌酐、MELD评分比较差异均无统计学意义(均P＞0.05);ALSS治疗后试验组各项指标较对照组均明显改善(均P＜0.01).试验组术前1 d MELD评分较进入等待名单时分值显著下降[(37.6±2.0)分比(41.4±2.2)分,P＜0.01],术前1 d与进入移植等待名单时MELD评分差值(AMELD)为-3.8分;对照组进入等待名单时与术前1 d的MELD评分E(40.6±1.7)分和(41.0±1.6)分]差异无统计学意义(P＞0.05),AMELD为+0.4分.试验组术中出血量和手术时间均显著低于对照组[(4 070.0±688.1)ml比(4 905.9±1 142.1)ml,(9.4±1.1)h比(10.5±1.0)h,P＜0.05和P＜0.01].试验组30 d和1年生存率分别为91%和82%,对照组为76%和59%,Log-Rank检验示两组生存率差异有统计学意义(P=0.044).结论 ALSS通过改善患者术前全身情况,减少术中失血量,有利于移植肝功能及时恢复,可提高重型肝炎肝移植患者的早期生存率.     

Reduced-size liver transplantation for infants and children.

Pediatric liver transplantation, although successful, was limited by the lack of available size-matched organs. Up to 25% to 50% of children died on the waiting list. RLT was initiated and developed to help alleviate donor shortage. Over time, RLT has proven to be an acceptable option for children requiring hepatic transplantation. In experienced centers survival rates are comparable to OLT, and long-term organ function is equally good. Future application of this technique may also provide more innovative approaches to pediatric liver transplantation.     

供受者血型不合肝移植2例病理观察

解放军南京军区福州总医院收治2例血型不合肝移植患者,病例1:患者男,因"原发性肝癌"在全麻下行经典式原位肝移植,供体血型为A型,受体为O型.病例2:患者女,患乙型肝炎病史,因"妊娠合并重症肝病,凝血功能障碍"行经典式原位肝移植,供体血型为B型,受体为O型.免疫组织化学染色后光镜下观察2例供受体血型不合肝移植的病理改变以及肝组织中各种免疫球蛋白和补体的沉积情况;探讨移植肝体液排异反应的诊断标准.结果显示2例移植肝的肝血窦内皮细胞上有不同程度IgG、IgM、IgA、C4c、C4d和C1q线状或颗粒状沉积,提示IgG等免疫球蛋白在肝窦内皮细胞上弥漫强阳性沉积,并伴有C4d等补体成分表达,可作为移植肝组织中存在体液排异反应的证据.     

肝移植术前等待患者的死亡原因分析

目的 调查分析住院等待肝移植患者的死亡原因,为加强肝移植术前等待患者的管理提供方向和依据.方法 回顾性分析我院2003年1月-2007年6月住院等待肝移植手术期间死亡的63例患者等待时间、治疗过程和死亡原因.结果 63例患者的平均住院等待时间为(32.53±17.21)d,重症加强治疗病房(ICU)住院时间为(12.75±9.77)d.等待期间上消化道出血、意识障碍、感染的发生率分别为47.62%、39.68%和74.60%.主要死因感染性休克和感染性多器官功能衰竭(MOF)以及曲张静脉破裂出血的病死率分别为39.68%和26.98%.血液净化治疗对肝性脑病治疗有效.结论 当前肝移植术前等待住院患者的主要死亡原因是感染和致命性上消化道出血.     

Current trends in cardiac transplantation

More than 30 years of experience in cardiac transplantation have resulted in cardiac transplantation being the primary therapeutic choice for patients under 65 years of age who have advanced heart failure and who remain symptomatic despite maximal medical therapy. The success and widespread use of cardiac transplantation is attributed to more liberal guidelines in recipient and donor selection, effective immunosuppressive therapy, close monitoring for rejection, and effective management of rejection. This article presents the current status of recipient and donor selection, surgical techniques, postoperative care, immunosuppression strategies, and rejection monitoring and management. Challenges associated with allocation of organs continue.     

Cardiac transplantation: candidate identification, evaluation, and management

For more than 40 years, cardiac transplantation has been a treatment option for patients with severe heart failure in whom optimal medical management is no longer effective. Critical care nurses are integrally involved in the care of patients with severe heart failure who may benefit from cardiac transplantation and are in a special position to recognize potential candidates for transplantation. Understanding patient selection criteria, the evaluation process, and how patients are managed while awaiting transplantation is key to the knowledge and skills required. It is also important to understand the allocation of donor hearts as part of this process. The waiting period for a suitable donor heart can be long and a patient's condition may deteriorate, requiring an increase in pharmacologic bridges with intravenous inotropic agents or mechanical bridges with circulatory assist devices. Critical care nurses become important as a personal bridge to transplantation through their education of patients and families and helping them cope with their fears during the waiting period. Critical care nurses who possess knowledge of patient selection and organ allocation processes along with the skills of caring for this complex patient population can contribute to better outcomes for patients with heart failure who may be candidates for cardiac transplantation.     

Cardioverter Defibrillator Therapy as a Bridge to Heart Transplantation

The prognosis of patients with severely impaired left ventricular function is poor, with an annual mortality rate of about 50%, and the majority die from sudden cardiac death. Heart transplantation is an accepted therapy for patients with end-stage heart disease; however, about 30% of candidates for transplantation die from sudden cardiac death while on the waiting list. It has been shown that implantable Cardioverter defibrillator (ICD) therapy has a low surgical mortality and is highly effective in the prevention of sudden death. Therefore, prophylactic ICD implantation may prevent sudden death in patients with end-stage heart disease while on the waiting list, and it is highly probable that patients with an ICD have a greater chance of survival until a donor heart becomes available. However, this hypothesis still has to be proven by prospective studies.     

肾移植后急性体液排斥反应:5年同一机构296例随访

背景:肾移植后急性体液排斥反应虽然发生率不高,但对移植物功能恢复可造成严重影响,是移植物早期丢失的主要原因.目的:分析肾移植后急性体液排斥反应早期诊断和防治的意义.方法:选择接受肾移植后规律随访的受者296例,其中移植前群体反应性抗体阳性受者26例,阴性受者270例.酶联免疫吸附试验动态监测肾移植受后外周血中的群体反应性抗体和供者特异性抗体,免疫组织化学染色观察穿刺活检组织中C4d的沉积及浸润淋巴细胞表面分子标记,按Banff 2005标准结合临床相关指标诊断急性体液排斥反应.结果与结论:26例移植前群体反应性抗体阳性受者中6例(23%)移植后发生了急性体液排斥反应,270例阴性受者中19例(7%)发生了急性体液排斥反应,差异有显著性意义(P < 0.01).发生急性体液排斥反应的患者中22例(88%)外周血清中检测到供者特异性抗体,271例无急性体液排斥反应的患者中仅1例检出供者特异性抗体,差异具有显著性意义(P < 0.01).急性体液排斥反应受者中C4d阳性率为80%,未发生急性体液排斥反应的患者C4d阳性率仅为6.7%,差异具有显著性意义(P < 0.001).肾移植后早期监测群体反应性抗体和供者特异性抗体水平,通过穿刺活检观察移植肾组织中的C4d沉积情况,可及时诊断急性体液排斥反应,有效改善移植物功能并提高移植物存活率.     

Laparoscopic donor hepatectomy

Laparoscopic liver resection has been applied to treat most indications for liver resection during the past two decades. According to the literature, patient numbers have increased exponentially as a result, and surgical difficulty has increased as well. In expert centers, laparoscopic anatomical hemihepatectomy and major liver resection more than 3 segments have become the acceptable treatment. Moreover, with surgical innovations and accumulated experience, living donor liver transplantation has become an established treatment choice for patients on the transplant waiting list. It is even considered an inevitable choice in regions with limited access to organs from deceased donors. However, significant morbidity and rare but catastrophic mortality are associated with donor hepatectomy and remain major concerns. Therefore, to decrease the incidence of complications, a minimally invasive approach in donor hepatectomy was adopted in the early 2000s. Initially, a minimally invasive approach was used for left lateral sectionectomy for pediatric liver transplant, then for laparoscopy‐assisted hemihepatectomy and pure laparoscopic/robotic right donor hepatectomy, and more recently, for adult living donor liver transplantation. The extent of procedure complexity and potential complications depends on the approach and the size of the graft to be harvested. Early results from expert teams have seemed promising in terms of shortened donor recovery and improved perioperative outcomes. However, the combination of these two highly sophisticated surgical procedures raise more concerns about donor safety, especially with regard to unexpected events during the operation. A high level of evidence is very difficult to achieve in this highly specialized surgical practice with limited penetration. Therefore, an international registry has been suggested to determine the risks and benefits before the use of laparoscopic right donor hepatectomy spreads.     

输注同基因骨髓间充质干细胞联合脾组织移植诱导肝移植大鼠的免疫耐受

背景:有研究显示在免疫抑制剂的作用下,同种脾脏细胞移植可诱导免疫耐受,使移植物长期存活.另有研究还显示异种骨髓间充质干细胞移植可延长移植肝存活时间.目的:观察输注与受体同基因骨髓间充质干细胞联合脾组织移植对诱导大鼠肝移植后免疫耐受的作用.方法:将受体Lewis大鼠以数字表法随机分为4组:急性排斥组行DA-Lewis大鼠原位肝移植;环孢素A组行DA-Lewis大鼠原位肝移植后灌胃给予环孢素A;干细胞组行DA-Lewis大鼠原位肝移植,同期输注异体Lewis大鼠骨髓间充质干细胞;脾组织移植组在干细胞移植组的基础上同期移植DA大鼠脾组织.观察各组生存期,肝功能情况,血清细胞因子水平,嵌合体的形成情况及肝脏病理变化.结果与结论:与其他各组相比,脾组织移植组大鼠存活时间明显延长,术后血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、总胆红索、白细胞介素2、干扰素Y水平明显降低(P<0.05),白细胞介素6、白细胞介素10明显升高(P<0.05),30 d后受体脾脏中供体阳性细胞明显升高(P<0.05).肝脏病理显示,环孢素A组和于细胞组移植肝仅呈急性轻度排斥反应,急性排斥组呈急性重度排斥反应,脾组织移植组未见明显排斥反应.说明大鼠肝脏、脾组织移植后输注同基因骨髓间充质干细胞町减轻移植肝的排斥作用,甚至诱导免疫耐受.     

Patients’ experiences of waiting for a liver transplantation

Organ transplantation has increased worldwide while the number of organ donors have not increased similarly. Consequently, the waiting period for transplant candidates is prolonged. Patient narratives have uncovered physical and psychosocial suffering in the transplantation process. However, relatively few studies have explored patients’ experiences in the actual waiting period. This qualitative study was conducted in Norway and aimed to describe patients’ experiences of being accepted as recipients of a new liver and their waiting following this decision. A sample of 21 patients with end‐stage liver disease, placed on the ordinary waiting list for a liver transplant, were interviewed in the hospital before they went home to wait for a compatible liver. Uncertainty related to life and death was a major issue, both in the waiting period and as a response to being put on the waiting list. Another central issue was their overwhelming lack of energy. Patients inferred a linear relationship between lack of energy, physical limitations and mental distress. Despite major advances in medical treatment, little follow‐up was given during the waiting period and most of the patients seemed resigned to the inevitability of their suffering. This raises issues of health personnel responsibility and a need to heighten awareness about patient suffering during the waiting period.     

Clinical management of patients with recurrent viral hepatitis after liver transplantation

Liver transplantation is indicated in end-stage chronic viral liver disease, but unless adequate prophylaxis is administered, the patient will in most cases develop recurrent hepatitis B (HBV) and C (HCV) virus infection. Today, patients receiving prophylaxis using nucleoside analogue drugs with or without specific immune globulin drugs in connection with orthotopic liver transplantation for HBV related cirrhosis, present low risk of relapse and high 5–10 year survival rates. Lamivudine was the first drug used in the prophylactic treatment, but this drug has increasingly been combined with or replaced by adefovir due to the low genetic barrier, which causes viral resistance. Most patients develop viral recurrence after orthotopic liver transplantation for HCV related cirrhosis, and in an elevated number of cases, cirrhosis and hepatic insufficiency set in after a few years. Prophylaxis before transplantation and pre-emptive treatment using interferon and ribavirin present numerous side effects resulting in reduction of doses and suspension of therapy, with consequently low sustained virological remission rates and risk of rejection.The treatment is better tolerated by patients with histologically confirmed chronic disease, but also in these patients virological remission rates are low. This pathology requires new therapeutic protocols and/or new drugs in order to obtain better compliance and better responses.     

不同来源供肾移植与术后环孢素A使用对患者术后肾功能的影响研究

目的 探讨不同来源供肾移植以及患者术后肾功能和环孢素A(CsA)用量范围.方法 对该院收治的接受肾移植的患者根据供肾的来源分为活体组以及尸体组,对两组患者的疗效、并发症、术后肾脏功能以及CsA的血药浓度进行比较.结果 活体组患者的疗效、肾脏功能以及肾脏存活率均优于尸体组,差异有统计学意义(P＜0.05).活体组患者CsA的利用率高于尸体组,差异有统计学意义(P＜0.05).结论 活体供肾有助于降低热缺血以及冷缺血时间,提高CsA的利用度以及患者肾脏5年生存率,降低患者急性排斥的发生,改善患者预后.     

Liver transplantation

Liver transplantation celebrated its twenty-fifth anniversary in 1988. However, only in the last decade has it been accepted as a viable treatment alternative for patients with end-stage liver disease. There currently are over 70 centers in the United States with liver transplant programs. Over 1500 transplants were performed in 1988, and there were 644 people awaiting suitable liver donors, with an average of 150 to 200 patients added to the list each month. This growth has resulted from many factors, including improved operative techniques and anesthetic management, immunosuppressive therapies, and improvements in donor recovery, which has served to increase the acceptable organs available for transplantation. The future of liver transplantation, however, may be somewhat uncertain. Will the cost of patient care continue to be supported by the economy? The goal of liver transplantation is simple: to provide the patient with a better quality and longer life. The question remains, is this a goal that society will deem financially feasible?     

Rh（D）血型不合的肝移植临床分析

背景：血型不合器官移植可能发生严重的排斥反应、移植物抗宿主病及溶血反应。目的：回顾分析Rh（D）阴性肝癌患者接受Rh（D）阳性供肝移植的方法及疗效,并结合文献复习探讨该方法的可行性。方法：1例Rh（D）阴性肝癌患者接受Rh（D）阳性供肝移植过程中,应保证供肝的良好灌洗,尽量减少出血,缩短手术时间,移植中移植后输注适量的异型红细胞及血浆。结果与结论：肝移植后,受者肝功能恢复正常,未发生急慢性排斥反应及输血相关并发症。随访1年,受者存活良好。说明在无合适供体的情况下,只要供肝得到充分灌洗、移植中控制出血、移植后采用合理的免疫抑制方案,Rh（D）阴性肝病患者移植Rh（D）阳性供肝可达到良好效果。