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。     

HBcAb阳性移植供肝用于乙型肝炎病毒相关性肝病患者的研究进展

随着肝移植技术的迅速发展,供肝短缺已经成为制约临床肝移植的瓶颈,因此拓展供肝来源成为目前肝移植临床的重点.我国为乙型肝炎大国,如果能够利用乙型肝炎病毒相关联供肝,不但增加供体数量,还能增加患者的生存希望并挽救更多生命.据国外文献报道,采用抗-HBc阳性肝脏不会影响移植物或患者的存活率,但是供体的可靠性值得关注.随着对边缘供肝的研究,将抗-HBc阳性供肝移植给乙型肝炎病毒相关性肝病患者,并且术后应用单一拉米夫定预防治疗,对移植后降低乙型肝炎复发的感染十分重要.抗-HBc阳性供肝应用于乙型肝炎病毒相关性肝病患者为将来拓展供肝标准、基因治疗等前端技术在肝移植中的应用拓展思路.我们采用抗-HBc阳性供肝用于乙型肝炎病毒相关性肝病患者的新进展及术后预防乙型肝炎复发的措施进行综述.     

边缘供肝的评估和应用

正肝移植是治疗终末期肝病的唯一有效手段。目前,供肝短缺是制约临床肝移植发展的瓶颈,大量病人在等待肝移植过程中死亡。另一方面,为了缓解供体器官的短缺,边缘供肝,也称作扩大标准供肝逐渐应用于临床肝移植。特别是在中国实施公民逝世后器官捐献(DCD)来源器官的背景条件下,供体由于在ICU抢救等过程中出现低血压、缺血、缺氧,以及大量血管活性药物的应用,DCD来源供体出现"边缘供肝"的情况     

高龄心脏死亡器官捐献供体肝移植研究进展

高龄供体供肝作为边缘供肝的一种,在有效解决供肝短缺的同时,也存在诸多高危因素,与肝移植术后并发症及病死率密切相关,但在控制好相关并发症及相关肝脏疾病的基础上,高龄供体肝移植在一定程度上是安全可靠的。本文从高龄肝脏退行性改变、高龄供体肝移植、高龄供体肝移植并发症、高龄供体肝移植高危因素、高龄心脏死亡器官捐献(DCD)供体选择标准思考等,就肝脏随年龄变化特点与高龄供体肝移植的近年研究进展作一综述,同时探究高龄DCD供体肝移植是否安全可行。     

劈离式肝脏移植8例

供肝短缺是肝移植手术的制约因素,虽然活体部分供肝、边缘供体增加了供体池,但都存在一定风险,数量也极其有限。劈离式肝脏移植（splitting liver transplantation,SLT）可一定程度上缓解供受者间的矛盾,尤其儿童供肝短缺问题。     

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。     

肝移植供肝切取技术及供肝的选择

作在法国参加23例供肝切取手术,对供肝的灌注,切取,修剪,保存等方面进行了观察。本组行全肝肝移植20例,劈离式肝移植2例,减体积肝移植1例,供肝全部存活,肝移植后供肝的质量与供体死亡前肝脏本身的质量,供体血液动力学情况,复苏情况,供肝切取技术,保存技术（保存液,时间,温度）以及受体高质量的血管吻合等因素有关,其中任何一步出现差错,将都严重影响供肝的功能。     

活体供肝肝移植成功的初步经验--附3例报告

目的 报告3例活体供肝肝移植成功的初步经验。方法 回顾性分析1例肝细胞癌伴肝硬化、1例先天性肝内胆汁淤积症及1例药物性肝炎病人活体供肝肝移植经过和供受体恢复情况。结果 供肝均取自病人父亲，1例为右半肝，另2例为扩大左外叶，供肝重量分别为835g、295g及320g。第1例供体术后有一过性黄疸，且有轻度胆漏，另2例供体术后恢复顺利，无手术并发症。3例病人手术均顺利，1例成人一成人活体供肝肝移植胆道重建为胆管端端吻合，术后定期行全身化疗预防肿瘤复发。2例成人-儿童活体供肝肝移植胆道重建为胆管、空肠Roux-en-Y吻合。3例病人均行肝静脉整形以保证静脉回流通畅。随访至今，供受体已分别健康生存16、14、13个月。结论 严格的病例选择，完善的术前准备，精细的手术操作及正确的术后处理是活体供肝肝移植成功的关键。     

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供肝缺乏一直是影响临床肝移植进一步发展的重要问题，活体肝移植被认为是缓解供肝来源缺乏的有效手段之一。作者于2006年11月19日成功施行1例成人间右3段加左半肝双供体活体肝移植手术。报道如下。     

边缘供肝面临的机遇与挑战

随着手术技术和术后免疫抑制治疗的不断突破与成熟,肝移植受者和移植物存活率显著提高,供肝短缺已成为限制肝移植临床发展的主要阻碍,如何扩大供肝来源也成为了当前迫切需要解决的问题。高龄供肝、脂肪变性供肝、病毒性肝炎供肝、心脏死亡器官捐献供肝等常见边缘供肝在临床肝移植中的使用已经取得了一定的突破性进展,但边缘供肝的使用仍存在较多限制。因此,本文对边缘供肝的定义,几种常见边缘供肝的应用及研究进展进行综述,探讨目前边缘供肝面临的机遇与挑战,旨在为临床肝移植供者池的扩大提供参考,造福更多终末期肝病患者。     

Liver transplantation for hepatocellular carcinoma: an Asian perspective

Liver transplantation is an established treatment modality for patients with hepatocellular carcinoma (HCC), creating a potential for disease-free, long-term survival. In Asia, due to a severe shortage of donors, resection remains the treatment of choice for patients with HCC and good liver functional reserve. The use of marginal donors, split liver grafts and grafts from living donors are potential solutions that are best performed in experienced liver transplant centres to ensure an optimal outcome. Ethical issues relating to living donor liver transplantation have yet to be fully addressed. The roles of therapies to limit tumour progression during the waiting period, such as transarterial chemoembolization, need to be further investigated in the setting of a prospective trial and their benefits better defined.     

Extended Criteria Donors in Liver Transplantation: Adapting Donor Quality and Recipient

Despite the progressive increase in the number of liver transplantations, the mortality on the waiting list remains between 5% and 10%, and patients have to deal with longer waiting periods. Facing this situation, transplant centers have developed alternatives to increase the number of grafts by accepting donors who were previously considered to be inadequate, because they are at higher risk of initial poor function and graft failure or may cause disease transmission. Currently, some marginal donors are being routinely used: elderly donors, steatotic grafts, non-heart-beating donors, hepatitis C virus-positive (HCV+) or hepatitis B core antibody-positive donors. These so-called marginal or extended-criteria donors were initially used in high-risk or urgent recipients; however, the number of marginal grafts has significantly increased, forcing the transplant community toward their more rationale use to maintain excellent results of liver transplantation. In this new scenario, the adequacy between donor and recipient may be paramount. Advanced donor age seems to be related to a greater graft failure rate in HCV+ recipients. Early survival seems to be significantly reduced when steatotic grafts are used in recipients with high Model for End-stage Liver Disease (MELD) scores. Moreover, a decreased survival has been observed among high-risk patients receiving organs from marginal donors. No benefit seems to exist when high-donor risk index grafts are transplanted into recipients with low MELD Scores. The recognition of various donor groups according to their quality and the need for good donor and recipient selection must lead us to define new policies for organ allocation of marginal grafts that may come into conflict with current policies of organ allocation according to the risk of death among patients awaiting a liver transplantation.     

Liver Transplantation from Deceased Donors Serologically Positive for Chagas Disease

The high mortality rates among patients waiting for liver transplantation has motivated the use of "marginal livers", among which are included livers from deceased donors serologically positive for Chagas disease (CD). The present work describes the outcome of orthotopic liver transplantation in six patients with severe liver disease (Child Pugh C), with livers from donors serologically positive for CD. Transplantations were performed from November 2000 to January 2005, and the patients received prophylactic treatment with benznidazole for 60 days, as a recommended by the Brazilian Consensus in Chagas Disease. The transplantation procedures presented no technical problems, and all the patients were discharged from hospital. Five of them did not present side effects demanding interruption of the prophylactic treatment. Four of the patients were clinically well over 1 year after transplantation (mean follow-up of 42.1 months), with negative serological results for CD. Two patients died, one of them 6 months post surgery of sepsis due to biliary complication and other one due to pulmonary (tuberculosis) complications. They were both serologically negative for CD. These results suggest that liver transplantation from CD donors, followed by benznidazole prophylactic treatment, is an important therapeutic alternative for severe liver disease.     

Clinical experiences in the Liver Unit, the Queen Elizabeth Hospital, United Kingdom

The present status of liver transplantation in th UK is described based on our clinical experience in the Liver Unit, Queen Elizabeth Hospital. In 1999, there were 161 cadaveric liver transplantations in the Liver Unit. The shortage of suitable donors for transplantation is widely recognized and is a worldwide problem. In order to solve this problem, "marginal donors" who would usually be refused on medical grounds have been used, and split-liver transplantation procedures have been developed in the Liver Unit.     

The use of marginal grafts in liver transplantation

Because of the shortage of organ supplies, more transplant programs have begun to use marginal grafts in liver transplantation. A number of single-center experiences with marginal grafts have yielded encouraging results, but recent analyses using nationwide databases show that outcomes are inferior to results with normal whole-liver grafts. Use of marginal grafts is still acceptable, however, and plays an important role in expanding the donor pool and decreasing mortality on the waiting list. In the broadest terms, national data and single-center experiences show that: (1) there is no limit in donor age for liver transplantation, (2) appropriate selection of steatotic livers improves outcomes, (3) prolonged graft ischemia is a preventable factor, (4) livers from donors with hepatitis B or C virus can be safely transplanted, and (5) adequate prophylaxis prevents recurrence of hepatitis B without significant graft loss. In addition, grafts procured after cardiac death are another growing source of marginal grafts. Transmission of malignancy from donors is rare but life-threatening. Reduced-size grafts from living-donor or split-liver transplantation have shown similar outcomes to whole-liver transplantation. In this review, we will discuss the current status of the utility of these marginal grafts in liver transplantation.     

Liver transplantation

Huge developments in the field of liver transplantation have occurred over the last 30 years. Improved immunosuppression regimens brought about by the introduction of ciclosporin and tacrolimus, the development of organ preservation solutions and enhanced perioperative care have meant that survival at 1 year following liver transplantation now reaches approximately 90%. The spectrum of disease now treated with liver transplantation has also grown to encompass a wide range of chronic disease and primary liver malignancy. Early referral to specialist centres affords better outcomes for potential recipients and has prompted the development of specific scoring systems to objectively assess liver failure and guide organ allocation. The consistent gap between the number of recipients and availability of organs, however, has driven many new developments such as split grafts and live donor transplantation. The use of the marginal graft is now commonplace in many centres in an attempt to reduce waiting list mortality. Here, we examine the origins and evolution of the specialty and describe some of the latest developments in the field of liver transplantation, with specific reference to the surgical techniques currently used as well as recent advances in immunosuppression therapy.     

Liver transplantation

Huge developments in the field of liver transplantation have occurred over the last 30 years. Improved immunosuppression regimens brought about by the introduction of cyclosporin and tacrolimus, the development of organ preservation solutions and enhanced perioperative care have meant that survival at 1 year following liver transplantation now reaches approximately 90%. The spectrum of disease now treated with liver transplantation has also grown to encompass a wide range of chronic disease and primary liver malignancy. Early referral to specialist centres affords better outcomes for potential recipients and has prompted the development of specific scoring systems to objectively assess liver failure and guide organ allocation. The consistent gap between the number of recipients and availability of organs however, has driven many new developments such as split grafts and live donor transplantation. The use of the marginal graft is now commonplace in many centres in an attempt to reduce waiting list mortality. Here, we examine the origins and evolution of the specialty and describe some of the latest developments in the field of liver transplantation, with specific reference to the surgical techniques currently used as well as recent advances in immunosuppression therapy.     

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.     

Liver transplantation from old donors into HCV and non-HCV recipients

BACKGROUND: Chronic liver failure due to HCV-related cirrhosis is the leading indication for liver transplantation in Western countries. Inferior long-term results have been reported for liver transplantation in HCV patients, especially when marginal donor livers are utilized. The aim of this study was to retrospectively analyze the outcome of liver transplantation from elderly donors in HCV versus non-HCV recipients. METHODS: One hundred seventy-nine patients receiving 204 liver transplantations were divided into four groups according to HCV positivity and donor age (> or <65 years). Long-term survivals were calculated by the Kaplan-Meier method. RESULTS: Grafts from donors of >65 years into HCV-positive patients displayed lower patient and graft survival rates than HCV-negative cases, although macrosteatosis was more frequent (55% vs 9%, P =.02) among organs used for non-HCV cases. Moreover, HCV-positive recipients transplanted with a donor aged >65 years had significantly lower patient and graft survival (40% vs 78% [P =.01] and 40% vs 68% [P =.06], respectively) than patients receiving a liver from a younger donor. CONCLUSIONS: Our retrospective analysis, although hampered by a small number of patients transplanted with an old liver, suggest that the results of liver transplantation with a donor graft >65 years of age into an HCV-positive recipient shows a worse outcome than those from younger donors. Older livers should be reserved for non-HCV cases.     

Continuous Resuscitation for Porcine Liver Transplantation From Donor After Cardiac Death

BackgroundTo solve the serious donor shortage, the demand is increasing for developing a new method to use the marginal donors, including donors after cardiac death (DCD). Continuous machine perfusion from ex vivo to in situ is a novel technique to overcome warm ischemia during organ grafting as an ischemia-free transplantation. Herein, we tested orthotopic and heterotopic ischemia-free liver transplantation in pigs and evaluated the perfusion characteristics of DCD grafts from ex vivo preservation to implantation.Materials and MethodsThe demonstration of ischemia-free transplantation was conducted using both orthotopic and heterotopic transplantation models. Warm ischemia time (WIT) was set at 60 minutes or 120 minutes in the DCD models. Recipients were humanely killed 3 days after transplant. Flow rates of portal vein and hepatic artery were set to 0.06 to 0.15 mL/min/g and 0.04 to 0.06 mL/min/g for the liver weight ratio, respectively.ResultsUnder the stable perfusion rate by machine perfusion, the average hepatic artery pressure of the liver graft after a WIT of 120 minutes was approximately 80 mm Hg higher than after WIT of 60 minutes. The recipient with liver graft of WIT of 60 minutes could not survive overnight. In heterotopic model, the recipient with 1 hour DCD liver survived until humanely killed.ConclusionsThe results of pressure monitoring in our DCD liver graft model indicate that pressures are influenced not only by thrombus formation but also by postmortem rigidity at 2 hours after cardiac death.