成人间双供体活体肝脏移植成功2例报告

目的供肝短缺是影响肝脏移植发展的主要因素之一，活体供肝是解决这一矛盾的重要措施，供者提供足够的肝脏是影响活体肝脏移植的重要因素。方法施行成人间双供体活体肝移植2例，1例由受者的两位姐姐分别提供左半肝作为供肝，另1例由受者母亲提供右半肝，由无心跳供者提供左半肝(采用劈裂方式，其另一部分肝脏同时为另一成人受者实施肝脏移植)作为供肝。结果术后供、受者肝功能均恢复良好。结论成人问双供肝活体肝脏移植可以为受者提供更大重量的肝脏，又可减少供者提供较多肝脏所带来的风险；双供肝一受者肝脏移植手术操作复杂。     

活体右后叶肝移植的应用进展

随着肝移植技术的发展,肝移植疗效显著提高,受者和移植物的存活率得到显著提升。但公民逝世后器官捐献仍不能满足肝移植需求,供肝短缺仍是阻碍肝移植进一步发展的关键因素。近年来,活体肝移植作为克服器官短缺的手段之一,广泛应用于终末期肝病患者的治疗。右后叶肝移植作为活体肝移植一种特殊类型,为进一步扩大活体肝移植潜在供者池提供了一种新的解决方案。本文从活体肝移植的发展概况、活体右后叶肝移植供者的选择、右后叶供肝获取的解剖学挑战以及右后叶供肝获取的手术技巧进行介绍,并对活体右后叶肝移植进行展望,以促进临床肝移植的进一步发展,造福更多终末期肝病患者。     

脂肪变性供肝冷缺血损伤的研究进展

肝移植是治疗终末期肝病的重要手段,然而供者短缺限制了肝移植的发展,如何扩大供肝来源成为学术界的难题。近年来非酒精性脂肪性肝病（NAFLD）供者比例增加,合理利用脂肪变性供肝是扩大供者池的可行方案。肝移植前供肝保存过程的冷缺血损伤增加了术后器官功能不全的发生率。因此了解脂肪变性供肝冷缺血损伤机制和干预措施尤为重要。脂肪变性供肝冷缺血损伤在细胞器层面具体表现为线粒体、溶酶体、内质网的损伤,蛋白层面主要表现腺苷酸活化蛋白激酶（AMPK）、乙醛脱氢酶2(ALDH2)、血红素加氧酶（HO）-1的表达增加。本文就脂肪变性供肝冷缺血损伤的研究进展及相关干预措施做一综述。     

肝脏移植热缺血损伤的研究进展

肝脏移植历经30余年的努力,已取得较大进展.进入90年代以后,肝移植每年以5*!000～8*!000例速度递增,成绩斐然.然而由于供肝来源远较受体为少,同时在脑死亡法尚未通过的国家如中国、日本等无法实施有心跳供者(heart-beating donor,HBD)供肝,迅速膨大的等待供肝人数与供体短缺的矛盾日益突出.目前在我国所采用的供肝几乎均来自无心跳供者(non-heart-beating donor,NHBD),供肝不可避免地经历了一段热缺血损伤,而且在冷保存及肝复流过程中会进一步遭受损伤.除经济、技术等因素外,供肝质量不好被认为是制约我国肝移植长期疗效提高的重要因素.供肝的缺血时间与灌注保存方法均影响肝移植并发症的发生和预后.在供肝保存的研究中,一般将供肝血循环的阻断到冷灌注开始这段时间,称热缺血.临床实践中全肝离体的热缺血时间一般认为不宜超过5 min.而一些实验证据提示肝脏所能耐受的实际热缺血时限可达60 min以上[1].进一步探讨肝脏移植热缺血损伤的时限及其与术后并发症及预后的关系有着极其重要的临床意义,并可最大限度地缓解供体器官短缺的现状,挽救更多濒临死亡的病人.     

脂肪变性供肝在肝移植中的应用现状与进展

肝移植是终末期肝病最有效的治疗措施,但器官供需的严重失衡已经成为制约肝移植进一步发展的关键因素.因此,如何合理使用边缘性供肝已成为肝移植临床的重点.常见的边缘性供肝有脂肪变性供肝、乙肝表面抗原阳性肝脏、超过60岁的高龄供者捐献的肝脏、冷缺血时间>14 h的肝脏、心脏死亡器官捐献(donation-after-circu...     

边缘供肝应用于肝脏移植的研究进展

目的 探讨边缘供肝的种类及其在肝移植中的应用前景。方法 复习国外有关边缘供肝应用于临床肝移植的最新进展。结果 高龄供体、缺血时限较长供体、脑死亡供体和脂肪肝供体是几种临床意义较大的边缘供肝。结论 虽然边缘供肝的使用给肝脏移植带来负面效应，然而其能扩大供肝来源且疗效确切。     

肝移植中应用边缘供肝的相关研究新进展

供肝短缺是当今制约临床肝移植发展的主要问题。临床上经常遇到脂肪肝供体、高龄供体、乙肝表面抗原阳性供体、冷缺血时限较长等边缘供肝（marginal donor）问题。我们就近年来国外有关边缘供肝在临床肝移植的应用及效果的最新进展做一综述。总体上说边缘供肝可以扩大供肝来源且疗效确切。     

腹腔镜活体肝移植供肝获取研究进展

活体肝移植已逐渐成为可以替代尸体供者肝移植治疗终末期肝病和早期肝细胞肝癌最有效的方法, 而腹腔镜活体供肝获取技术在活体肝移植中扮演着越来越重要的角色。本文介绍腹腔镜活体供肝获取在活体肝移植中的应用情况, 从供者选择、腔镜辅助活体供肝获取、腹腔镜左外叶获取、腹腔镜左半肝获取及腹腔镜右半肝获取等几个方面综述腹腔镜手术在活体肝移植中的特点, 从而为提高供者安全性提供新的研究思路。     

活体右半供肝血管和胆管变异及重建处理

成人到成人的活体右半肝移植在东、西方国家已成为一种可以接受的治疗终末期肝病的有效措施。由于尸体供器官的缺乏以及肝移植适应证的扩大，供需矛盾愈来愈突出，在东方国家脑死亡供器官不被接受，这种矛盾更加明显，很多终末期肝病患者在等待肝源过程中死亡。成人间活体右半肝移植缩短了受体等待移植的时间，一定程度上缓解了器官短缺，尤其适用于急性肝功能衰竭患者，在一些国家甚至成为主要的供器官来源，例如在日本。1994年日本Yamaoka等成功开展了世界首例活体右半肝移植，但并非在成人间。1997年香港首先开展成人间活体右半肝移植，即活体扩大右半肝移植。自此，成人间活体右半肝移植在世界范围的各大移植中心广泛开展，但在手术技术上存在一些争论。现就成人间活体右半肝移植供肝血管及胆管解剖变异和在受体重建时的相应处理复习文献，并总结如下。     

活体肝移植的供肝处理技巧

目的 探讨活体肝移植术供肝的选择，切取和修整，方法 1997至2001年期间，第四军医大学西京医院共完成活体肝移植术3例。其中2例是儿童活体肝移植术，另1例是成人辅助性原位活体肝移植术，供肝切取均为左外叶，供者术中作必要的肝周韧带游离和肝门解剖，超声刀切取供肝，不阻断肝脏血流。结果 供者手术时间为5-6.5h，失血量为200-400ml，无并发症发生。目前所有的供者肝功能均正常。恢复正常的工作和生活。结论 左肝外叶切除对供者是非常安全的。一般无手术并发症发生。     

脑死亡来源供肝肝移植9例临床分析

目的总结使用脑死亡来源供肝肝移植的临床经验,初步分析脑死亡来源供肝应用于临床的安全性。方法2006年1月至2007年12月我院器官移植科共实施9例脑死亡来源供肝肝移植。供体年龄16～43岁,死于颅脑外伤7例,死于脑血管意外2例,器官切取前平均动脉压(105±5.2)mmHg(1mmHg=1.333kPa)(6例需使用升压药物),肝功能检测丙氨酸转氨酶(175±40)U/L,天冬氨酸转氨酶(180±46)U/L,总胆红素(40±8.6)mmol/L。受者年龄(48.6±10.1)岁,男性8例,女性1例;术前诊断为肝硬化5例,肝癌4例,术前MELD评分(27.6±6.7)分。结果供肝冷缺血时间为(7.4±2.8)h,所有患者手术顺利。1例于术后7天死于肾功能衰竭。8例受者康复出院并随访6～24个月,1例于术后24个月死于肿瘤复发,其他并发症发生包括急性排斥反应2例,胆道狭窄并感染1例,胆道缺血1例,肺部感染1例。结论按照我们选择脑死亡供肝的原则,肝移植受者术后近期及中期预后良好,具有临床应用前景。     

Current status and recent advances of liver transplantation from donation after cardiac death

The last decade saw increased organ donation activity from donors after cardiac death (DCD). This contributed to a signif icant proportion of transplant activity. Despite certain drawbacks, liver transplantation from DCD donors continues to supplement the donor pool on the backdrop of a severe organ shortage. Understanding the pathophysiology has provided the basis for modulation of DCD organs that has been proven to be effective outside liver transplantation but remains experimental in liver transplantation models. Research continues on how best to further increase the utility of DCD grafts. Most of the work has been carried out exploring the use of organ preservation using machine assisted perfusion. Both ex-situ and in-situ organ perfusion systems are tested in the liver transplantation setting with promising results. Additional techniques involved pharmacological manipulation of the donor, graft and the recipient. Ethical barriers and end-of-life care pathways are obstacles to widespread clinical application of some of the recent advances to practice. It is likely that some of the DCD offers are in fact probably "prematurely" of-fered without ideal donor management or even prior to brain death being established. The absolute benef its of DCD exist only if this form of donation supplements the existing deceased donor pool; hence, it is worthwhile revisiting organ donation process enabling us to identify counter remedial measures.     

心脏死亡供体肝移植12例初步经验

目的总结心脏死亡供体（DCD）肝移植的具体流程和临床经验。方法回顾性分析2008年10月至2012年12月中山市人民医院12例DCD临床资料、供体维护、器官获取、受体围手术期及预后等。结果12例供体均为脑、心双死亡供体,按标准成功完成了肝脏捐献及获取流程。其中3例使用体外膜肺氧合技术（ECMO）维持至器官获取。供肝热缺血时间0-30（16．5±7．0）min。12例受体均顺利植入供肝,无围手术期死亡。术后胆道并发症2例,肿瘤复发1例,死亡2例。结论DCD供体肝移植能获得较满意的效果。通过快速获取器官、合理利用ECMO,能提高器官捐献成功率、减少供肝热缺血时间及冷缺血时间。     

Liver graft preservation methods during cold ischemia phase and normothermic machine perfusion

The growing demand for donor organs requires measures to expand donor pool.Those include extended criteria donors, such as elderly people, steatotic livers,donation after cardiac death, etc. Static cold storage to reduce metabolic requirements developed by Collins in late 1960 s is the mainstay and the golden standard for donated organ protection. Hypothermic machine perfusion provides dynamic organ preservation at 4°C with protracted infusion of metabolic substrates to the graft during the ex vivo period. It has been used instead of static cold storage or after it as short perfusion in transplant center. Normothermic machine perfusion(NMP) delivers oxygen, and nutrition at physiological temperature mimicking regular environment in order to support cellular function. This would minimize effects of ischemia/reperfusion injury.Potentially, NMP may help to estimate graft functionality before implantation into a recipient. Clinical studies demonstrated at least its non-inferiority or better outcomes vs static cold storage. Regular grafts donated after brain death could be safely preserved with convenient static cold storage. Except for prolonged ischemia time where hypothermic machine perfusion started in transplant center could be estimated to provide possible positive reconditioning effect. Use of hypothermic machine perfusion in regular donation instead of static cold storage or in extended criteria donors requires further investigation. Multicenter randomized clinical trial supposed to be completed in December 2021. Extended criteria donors need additional measures for graft storage and assessment until its implantation. NMP is actively evaluating promising method for this purpose.Future studies are necessary for precise estimation and confirmation to issue clinical practice recommendations.     

Factors Affecting Graft Survival After Adult/Child Split-Liver Transplantation: Analysis of the UNOS/OPTN Data Base

When considering advocacy of split-liver transplantation, it is important to understand whether comparable outcomes can be achieved. The goal of this study was to identify donor and transplant characteristics predictive of comparable outcomes by risk factor analysis. Using the United Network for Organ Sharing/ Organ Procurement and Transplantation Network data base between January 1996 and May 2006, first time adult/child split cases (568 adults, 508 children) were examined. In multivariate analysis, recipient medical condition (hospitalization), status 1 assignment, ABO incompatibility, donor age (>40 years), donor body weight (≤40 kg), calculated whole graft volume to recipient body weight ratio (cGRWR ≤1.5%) and no sharing between centers were significant risk factors in adult recipients.
Recipient diagnosis of tumor, dialysis prior to transplant, recipient body weight (≤6 kg), donor age (>30 years), donor history of cardiac arrest after declaration of death and cold ischemia time (CIT > 6 h) increased the risk of graft failure in pediatric recipients. The livers from young donors showed comparable outcomes to whole deceased liver transplantation (LT) when other transplant-related risk factors were minimized in adult recipients. Reducing CIT is important to obtain comparable outcomes to living donor LT in pediatric recipients.     

Duration of Donor Brain Death and its Influence on Kidney Graft Function

Short- and long-term rates of success after cadaveric kidney transplantation are significantly inferior to those from living related or unrelated donors. The major difference between cadaveric and living donation is brain death. In the present study we analyzed the influence of duration of brain death on short- and long-term graft function after cadaveric kidney transplantation. The interval between declaration of donor brain death and the beginning of the cold ischemia time before graft explantation was defined as duration of brain death (DBD). The influence of DBD on incidence of primary graft function and on duration of delayed kidney graft function as well as on kidney graft survival was analyzed in 1106 patients transplanted in one center and confirmed in a validation study of a second series of 752 kidney graft recipients from another transplant center. Kidney grafts harvested from donors with longer DBD (>470 min) exhibited a significantly higher incidence of primary graft function and a significantly better graft survival rate in comparison to kidneys from donors with a shorter DBD (<470 min). The tendency of these results could be confirmed in an independent validation study; however, the differences were not statistically significant. Although the dramatic hemodynamic and immunological changes in brain-dead donors may impair the quality of a potential kidney transplant, a longer duration of donor brain death did not deteriorate early and long-term kidney graft function.     

公民身后器官捐献肝移植术后早期细菌和真菌感染并发症的临床特点与危险因素分析

目的对比分析公民身后器官捐献与传统司法途径器官捐献肝移植术后早期受体细菌和真菌感染并发症的临床特点,探讨公民身后器官捐献肝移植受体术后感染的危险因素。 方法回顾性研究2011年1月至2013年12月间本中心实施的公民身后器官捐献肝脏供、受体（研究组）和司法途径来源器官捐献的肝移植受体病例（对照组）,比较两组受体术后细菌、真菌感染的临床特点和预后,分析术后受体感染的危险因素。 结果共纳入公民身后器官捐献肝脏供体43例;研究组受体72例,对照组受体80例。研究组受体的细菌、真菌感染总发生率显著高于对照组（47.2% vs 31.2%）（χ²=4.071,P=0.044）。研究组受体术后1周内的细菌感染率高于对照组（64.5% vs 38.2%）（χ²=6.133,P=0.018）。供体捐献前感染和开放性创伤史是术后受体感染的独立危险因素（P=0.025、0.031）。4例疑似供体来源性受体感染,占研究组总感染例数的11.8%（4/34）。 结论使用公民身后器官捐献来源器官的肝移植术后受体感染发生率显著高于传统司法途径来源,发生细菌感染的时间更早。供体器官捐献前存在感染和有开放性创伤是肝移植术后受体发生感染的危险因素。     

Liver transplantation from an uncontrolled non-heart-beating donor maintained on extracorporeal membrane oxygenation

Liver transplantation, a definitive treatment for end-stage liver disease, has achieved excellent results. However, potential recipients on the waiting list outnumber donors. To expand the donor pool, marginal grafts from older donors, steatotic livers, and non-heart-beating liver donors (NHBD) have been used for transplantation. Reducing the warm ischemia time of NHBD is the critical factor in organs preservation. Liver transplantation using grafts from NHBD have been reported to display a high incidence of primary graft nonfunction and biliary complications. The authors report a liver graft donor who was maintained on extracorporeal membrane oxygenation (ECMO) after successful cardiopulmonary resuscitation. Core body temperature was 5 degrees C. Procurement of the liver using a rapid flush technique was performed 4 hours after instituting ECMO. Graft function recovered fully after transplantation. In conclusion, ECMO may be used to reduce warm ischemia time in liver grafts obtained from uncontrolled NHBD, thereby increasing graft salvage rates.     

The cumulative effects of cold ischemic time and older donor age on liver graft survival

INTRODUCTION: To provide greater equity among those awaiting a liver transplant, expanded geographic sharing of cadaveric organs has been proposed. A potential unintended consequence could be an increase in cold ischemia time (CIT), which may be deleterious to organs from older donors. This study sought to quantify the relative risk (RR) associated with increased CIT among older donors. METHODS: A retrospective study examining 18,787 liver transplants within the United Network for Organ Sharing database from 2002 to 2006 was performed. Cox Regression analysis was used to model the RR of graft loss with respect to increased CIT among older donors (>60 years) relative to younger donors (<60 years), while controlling for multiple donor and recipient characteristics. RESULTS: Relative to younger donors with minimal CIT (<6 h), a 73.0% increase in the risk of graft loss was observed for older donors with a CIT between 8 and 10 h, a 56.9% increase for CIT between 10 and 12 h, and a 92.7% increase for a CIT of 12 or more hours. Additionally, the RR of graft loss for older donors with minimal CIT (<6 h) was greater than the RR for younger donors with a CIT between 0 and 12 h. CONCLUSION: The additive effects of increased donor age and cold ischemic time greatly impair graft survival. Quantification of the adverse nature of increasing CIT as a potential consequence of wider geographic organ sharing should be considered as allocation policies are modified to improve recipient equity in the face of an aging donor pool.     

心脏死亡供体经典原位肝移植的单中心临床研究

目的总结心脏死亡器官捐献（donation after cardiac death,DCD）供体供肝获取及应用于肝移植的临床经验和可行性。方法2011年11月至2012年9月,西安交通大学第一附属医院采用Maastricht标准或中国标准,共获取18例DCD供肝,于该院完成经典原位肝移植14例,送往其他移植中心3例,放弃1例。对18例供体与在该院完成肝移植的14例受体的临床资料进行回顾性分析,了解供肝情况、受体围手术期及随访结果。结果18例供体中符合Maastricht标准Ⅲ类5例、V类2例,符合中国标准Ⅲ类（即脑一心双死亡标准器官捐献,donation after brain death plus cardiac death, DBCD）11例。按规范器官获取流程取得供肝。供肝的热缺血时间为11～18min,平均为14．5min;冷缺血时间为90—600min,平均为350min。14例受体均顺利完成移植手术。其中12例受体预后良好,肝功能逐渐恢复,未出现原发性移植肝无功能、血栓形成、排斥反应,但2例出现胆道狭窄并发症,经胆道支架置人术后引流通畅;重症监护室（ICU）治疗时间平均7d,术后住院时间平均23d,病情稳定后出院。1例受体术后2d死于肝衰竭,其供体原发病为冠状动脉粥样硬化性心脏病,需给予大量多巴胺维持其血压;另1例于术后当日死于腹腔内大出血,其供体为重症哮喘、心肺复苏后死亡。12例受体者平均随访时间为6个月,总体存活率为85％,肿瘤患者尚未发现复发转移。结论DCD可以扩大供肝来源且近期效果良好,具有可行性。实施可控型DCD捐献,严格掌握供者适应证、加强器官评估、缩短热缺血时间和冷缺血时间,是保障供肝质量的重要因素。