Living donor liver transplantation in India

Liver transplantation is currently in its golden period in India. The number of transplants being performed and the steady increase in the new programs that have emerged over the last decade is a testimony to it. The growth was not smooth, especially in the early years. But a multipronged approach in developing infrastructure and the involvement of multidisciplinary teams in the management of transplant patients has had a major positive impact on the outcome and as a result a positive impetus to the growth of this specialty in India. To date, the majority of transplants performed in India are live donor liver transplants. Deceased donation is more sporadic and concentrated in a couple of regions. With phenomenal increase in transplant activity in India, there is huge potential for streamlining data sharing among programs in India and with the rest of the world to ultimately benefit the transplant community.     

Feasible usage of ABO incompatible grafts in living donor liver transplantation

Background

The use of ABO incompatible (ABOi) graft in living donor liver transplantation (LDLT) has not been an established procedure worldwide.

Methods

Four hundred and eight adult LDLTs, using ABOi (n=19) and non-ABOi (n=389) grafts, were performed as a single center experience.

Results

In ABOi-LDLT group (n=19), median isoagglutinin titer before plasma exchange (PE) at LDLT and after LDLT (max) was ×256, ×32 and ×32, respectively. Rituximab was given at 21.8±6.1 days before LDLT and PE was performed 3.7±1.6 times. Although ABOi-LDLTs had increased rate of splenectomy (89.4% vs. 44.7%, P<0.001) and lower portal venous pressure (PVP) at the end of surgery (13.8±1.1 vs. 16.9±0.2 mmHg, P=0.003), other operative factors including graft ischemic time, operative time and blood loss were not different between the groups. Although ABOi-LDLTs had increased incidence of cytomegalovirus infection (52.6% vs. 22.9%, P=0.007), other post-transplant complications including bacterial sepsis and acute rejection were not different between the groups. The 5-year graft survival rate was 87.9% in ABOi-LDLTs and 80.3% in non-ABOi-LDLTs (P=0.373).

Conclusions

ABOi-LDLT could be safely performed, especially under rituximab-based protocol.     

活体肝脏移植猪动物实验训练模型的建立

目的建立活体肝脏移植猪动物实验训练模型,让外科手术人员能够学习和掌握活体肝移植所必需的技巧。方法施行6组供、受体共12头猪活体肝移植模拟手术,每组猪性别不限。结果5头受体猪存活至术后第7天,并进行无痛处死;1头受体猪于术后第2天死于创面广泛出血。4头受体猪发生了胆瘘,均没有发生显著的胆汁性腹膜炎。结论本实验模型的各个步骤,基本整合了进行活体肝移植所需要的所有外科操作技巧;作为一种模拟活体肝移植动物实验模型,能够有效地应用于对移植人员进行人活体肝移植手术技巧的训练。     

Living donor liver transplantation in the USA

Living donor liver transplant (LDLT) accounts for a small volume of the transplants in the USA. Due to the current liver allocation system based on the model for end-stage liver disease (MELD), LDLT has a unique role in providing life-saving transplantation for patients with low MELD scores and significant complications from portal hypertension, as well as select patients with hepatocellular carcinoma (HCC). Donor safety is paramount and has been a topic of much discussion in the transplant community as well as the general media. The donor risk appears to be low overall, with a favorable long-term quality of life. The latest trend has been a gradual shift from right-lobe grafts to left-lobe grafts to reduce donor risk, provided that the left lobe can provide adequate liver volume for the recipient.     

活体肝移植治疗终末期肝病

目的 探讨活体肝移植(1iving donor liver transplantation,LDLT)供、受者术前评估和手术方式的选择.方法 回顾性分析1995年1月至2007年10月我中心95例LDLT患者的临床资料.良性终末期肝病92例,其中Wilson病45例;肝脏恶性肿瘤3例.结果 供肝切取不带肝中静脉右半肝31例,带肝中静脉右半肝3例,带肝中静脉左半肝51例,不带肝中静脉左半肝或左外叶10例.所有供者术后顺利恢复,均未出现严重并发症.受者随访1～86个月,良性终末期肝病受者1、3、5年累积生存率分别为89%(82例)、78%(71例)和73%(67例),其中Wilson病受者1、3、5年累积生存率分别为92%(42例)、89%(40例)和76%(34例).3例肝脏恶性肿瘤患者死亡2例,1例长期生存.供、受者铜代谢均恢复正常.结论 建立供者安全保障体系是LDLT开展的先决条件,选择合理的手术方式是提高受者生存率的关键.亲体肝移植是治疗Wilson病的有效手段.     

Living donor liver transplantation: effect of the type of liver graft donation on donor mortality and morbidity

To investigate the influence of the type of liver graft donation on donor mortality and morbidity. The clinical course of 87 living liver donors operated on at our center between 2002 and 2009 was retrospectively analysed and data pertaining to all complications were retrieved. No donor mortality was observed and no donor suffered any life‐threatening complication. Four donors (4.6%) developed biliary leakage, nine (10.3%) had to be readmitted to hospital and six (6.9%) required some or other type of reoperation related to the previous liver donation. Reoperations included incisional or diaphragmatic hernia repair (n = 4), biliary leakage repair (n = 1) and segmental colon resection combined with diaphragmatic hernia repair (n = 1). There was a statistically significant difference in hospital stay (P < 0.001), autologous blood transfusions (P < 0.001) and operating time (P < 0.005) when right lobe donations (Segments V–VIII) were compared with left lobe (Segments II–IV) and left lateral lobe (Segments II–III) donations, whereas no difference was found between these groups regarding hospital readmission, operative revisions and the incidence or severity of complications. Right lobe donation was associated with prolonged hospital stay, increased blood transfusions and prolonged operating time when compared with left and left lateral lobe donation, whereas donor mortality and morbidity did not differ between these groups.     

Guidelines for donor selection and an overview of the donor operation in living related liver transplantation

Guidelines for donor selection and an overview of the donor operation are reported on the basis of our experience with 120 cases of living related liver transplantation (LRLT) in pediatric patients. Once the parents had clearly expressed their desire to serve as donors, tests were performed to functionally and anatomically screen the donor livers to determine whether or not the parents' general physical condition allowed them to serve as donors. We then evaluated which of the two parental candidates was more suitable as a donor. The wishes of the family as to which parent should serve as donor was considered secondary and taken into account only in a few cases in which certain functional and/or anatomical abnormalities were uncovered that made the prime candidate less suitable. For the 120 LRLTs, 135 candidates were evaluated as potential donors, 15 (11.1%) of whom were rejected for various reasons. The mean volume of blood loss during the donor operation decreased significantly from 489 g in the first 60 LRLTs to 390 g in the latter 60 LRLTs; this was accompanied by a significant decrease in the mean volume of autologous blood transfused from 449 g to 390 g. Mean cold ischemia time of the graft increased significantly from 71.4 to 128.0 min, while mean operation time conversely decreased from 6.7 to 6.2 h. Bile leakage from the cut surface of the remnant lver, which was the only postoperative surgical complication encountered, was noted in five cases. We conclude that donor candidates should be strictly selected according to basic guidelines, taking into account both the results of preoperative screening and the wishes of the family. With this accumuled experience, we have been able to simplify our LRLT operative procedure, resulting in decreases in blood loss volume, blood transfused, and operation time.     

Donor screening algorithm for exclusion of thrombophilia during evaluation of living donor liver transplantation

Ogawa H, Fujimoto Y, Yamamoto K, Hata T, Nagai S, Kamei H, Arikawa T, Nakamura T, Kiuchi T. Donor screening algorithm for exclusion of thrombophilia during evaluation of living donor liver transplantation.
Clin Transplant 2011: 25: 277–282. © 2010 John Wiley & Sons A/S. Abstract: Living donor liver transplantation (LDLT) has evolved based on the premise that donor safety is most important. In 2005, we encountered a donor who developed a pulmonary embolism during the early post‐operative period. As it is important for donors to be healthy, most risk factors related to perioperative thrombosis, such as obesity, age, and malignancy are used as exclusion criteria during the evaluation process. We speculated that thrombophilia not detected by conventional laboratory examinations may cause post‐operative thrombotic complications and should be investigated by application of additional parameters, including protein S, protein C, antithrombin III, anti‐β2‐glycoprotein I antibodies (anti‐β2GPI), and lupus anticoagulant. From July 2005 to June 2007, we evaluated 44 donor candidates for LDLT using our novel algorithm for screening of thrombophilia, which revealed two suspected candidates (one with low protein S, one with low protein C, and positive anti‐β2GPI findings), who were subsequently excluded from the donor pool. Thereafter, all donor hepatectomies, which included two borderline donors given anticoagulants perioperatively, were performed without complications. Four donors (two suspected, two borderline) would not have been recognized without additional screening. In conclusion, we were able to detect thrombophilia and avoid donor thrombosis using additional screening criteria and our novel algorithm.     

Living donor financial assistance programs in liver transplantation: The global perspective

Living donor liver transplantation (LDLT) has increased availability of liver transplantation, particularly in countries with limited access to deceased organ donors. It is unclear how individual countries address the financial impact of donation for potential living donors. Herein, living liver donor financial supports were examined, focusing on countries performing ≥10 LDLT per year in the World Health Organization Transplant Observatory. Categories included health insurance coverage, reimbursement of lost wages, employment protection, and other incentives designed to promote living liver donation. Overall, 26 countries have some form of asssistance in removing disincentives to ease the financial burden of living donation, ranging from childcare, accommodations, meals, and travel reimbursement, to coverage of medical complications post-donation. Most countries provide donation-related medical coverage. Fourteen provide reimbursement of lost wages and/or paid time off. Several unique programs were designed to incentivize living donation, including free entry to museums and observatories, parking and airline discounts, and exemptions on mortgages and medical deductibles. This study highlights the broad range of programs designed to support living liver donation in high-volume LDLT countries. The data collected in this study can provide a framework for other nations to propose and implement ethical reimbursement and incentivization for living liver donors.     

精准肝脏外科理念在儿童活体肝移植供肝切取术中的临床价值

目的 探讨精准肝脏外科理念在儿童活体肝移植供肝切取术中的临床价值.方法 回顾性分析2012年12月至2014年1月上海交通大学医学院附属仁济医院收治的58例儿童活体肝移植供者的临床资料.术前对供者行CT等检查,将二维影像学数据进行三维重建,评估供者肝内胆管和血管情况,并对肝左动脉和肝左静脉解剖结构进行分型,测算供者标准肝脏体积、拟切取肝脏体积和受者标准肝脏体积,模拟手术操作,制订手术方案.采取精准肝切除切取供肝.采用门诊和电话方式进行随访,随访时间截至2014年4月.结果 58例儿童活体肝移植供者术前CT血管造影检查示肝左动脉Ⅰ型28例、Ⅱ型10例、Ⅲ型20例、无Ⅳ型供者;肝左静脉Ⅰ型35例、Ⅱ型23例.三维重建预测拟切取肝脏体积为(243±65) mL.58例供者均成功完成供肝切取术,其中7例为左半肝切取,51例为肝左外叶切取.2例供者行胆囊切除.术中实际切取肝脏体积为(255±59) mL,拟切取肝脏体积平均误差率为4.94％.移植物质量与受者体质量比为3.3％±1.0％.手术时间为(260±89)min,术中出血量为(181±35)mL,仅1例供者术中输RBC 2 U.供者术后胃肠功能恢复时间为(2.0±1.1)d,术后拔除引流管时间为(3.0±1.2)d,术后住院时间为(7±3)d,出院时所有供者血清WBC、Hb、ALT、AST、TBil、DBil、AIb等指标水平正常.2例供者术后发生并发症,分别为切口少量渗血和脂肪液化,均经对症治疗后痊愈.58例儿童活体肝移植供者术后均获得随访,中位随访时间为8.7个月.供者恢复良好,随访期间无并发症发生.结论 精准肝脏外科理念应用于儿童活体肝移植供肝切取术,切取准确率高、供者肝功能损害小、术后并发症少、恢复快.     

Duct-to-duct biliary reconstruction in adult-to-adult living donor liver transplantation

In living donor liver transplantation (LDLT), Roux-en-Y hepaticojejunostomy has been a standard technique for biliary reconstruction because the majority had been pediatric patients with biliary atresia. Adult-to-adult LDLT using the right lobe graft has recently been developed and we introduced duct-to-duct biliary reconstruction (hepaticohepaticostomy) in such cases. The aim of this study is to evaluate the feasibility of this procedure in adult-to-adult LDLT. From August 2000 to October 2001, five patients underwent adult-to-adult LDLT using the right hepatic lobe and were followed for more than 6 months at our institution. All patients underwent duct-to-duct biliary reconstruction (single hepaticohepaticostomy in one, multiple in four). For the grafts with multiple bile ducts, various techniques were used for reconstruction. In all patients, oral intake could be started early after the operation, and biliary leakage was not encountered. One patient developed two episodes of acute cholangitis who later developed biliary anastomosis stricture which required percutaneous dilatation at 11 months postop. However, otherwise, there were no infectious complications postoperatively. We conclude duct-to-duct biliary reconstruction is feasible and effective in adult-to-adult LDLT.     

Clinical application of arterialization of portal vein in living related donor partial liver transplantation

Arterialization of the portal vein was employed during hepatic arterial reconstruction in our first few clinical experiences of partial liver transplantation using liver grafts obtained from living related donors. This procedure reduced the time required for revascularization of the grafts to about 25 min, and could in fact reduce the ischemic phase of the grafts. Repeated practice of the clinical transplantation technique has shortened the time needed to complete vascular reconstruction, eliminating the need for this procedure in most of our subsequent cases. In many clinical cases, however, there may be emergency situations which require vascular reconstruction, resulting in a prolongation of ischemic phase and the deterioration of the cellular viability of the graft. In such situations, arterialization of the portal vein can be a useful way to prevent the prolongation of the ischemic phase and to rescue the graft.     

活体肝移植供体手术及术后管理（附22例临床分析）

目的 探讨提高活体肝移植供体手术安全性和加强术后管理的措施。方法 回顾性分析北京大学人民医院2003年2月至2009年6月22例活体肝移植供体的临床资料,总结供体术前评估、手术技术、术后并发症及随访情况。结果 术前对供体进行三步法评估,术中采用超吸刀 （CUSA）进行肝脏实质分离,术后定期随访。供肝移植物包括肝左外叶2例、左半肝6例、扩大左半肝1例、右半肝5例和扩大右半肝8例。1例在术后早期出现腹腔内出血,1例合并胸水,1例枕后皮下血肿,其他供体未出现严重并发症,术后肝功能迅速恢复正常,随访至今无供体死亡。结论 活体肝移植供体手术复杂,严格术前评估,术中精细操作,术后加强随访是提高活体肝移植供体安全的重要保证。     

Living related liver transplantation

Liver transplantation from a brain death donor has not yet been accepted in Japan. The only alternative method at present is transplantation from a living donor. After the first successful living related liver transplantation was performed by Strong in Brisbane, Australia, Japanese hepatic and transplant surgeons also began to perform such operations. As of February 1991, 16 living related liver transplantations had already been performed in Japan, mainly for children with biliary atresia. Five of these patients subsequently died, however, our patient has survived more than 1 year, and she is presently leading a normal school life. The most important issue regarding living related liver transplantation is to ensure the donor's safety. For this purpose, we conducted a preoperative banking of the donor's own blood and plasma. In addition, a selective vascular occlusion was carried out to reduce blood loss during the resection of the liver. Intraoperative color Doppler ultrasonography was introduced for evaluating the circulation of the graft. By using this modality, the following three points were able to be accurately estimated in order to obtain optimal graft perfusion: 1) The most suitable position for the graft to be fixed to the abdominal wall, 2) whether or not the abdominal wall could be closed and 3) the indication for a ligation of the collateral veins to form a porto-systemic shunt. Thanks to these procedures, living related liver transplantations have now become an acceptable transplant method, however, a transplantation from a cadaver that is brain dead but still has a beating heart is still absolutely necessary for adult recipients. Therefore, in the future, both methods should be performed.This report is the gist of a paper read at the 91st Annual Meeting of the Japanese Surgical Society, Kyoto, Japan, 1991     

Living donor liver transplantation for pediatric patients with metabolic disease vs. deceased donation

BackgroundThere are conflicting reports on the outcomes of patients with metabolic liver disease after liver transplantation. We aimed to compare the outcomes of living donor liver transplantation (LDLT) for metabolic disease vs orthotopic liver transplantation (OLT) from deceased donation.MethodsClinical data of 89 patients undergoing liver transplantation for the treatment of metabolic disorders were reviewed. Pre- and peri-transplant demographics, survival rate, complications and laboratory test data were collected and analyzed.ResultsFor the 89 patients, only 2 died by the end of the last follow-up. The post-transplant EAD rate and severe complications were higher for OLT than LDLT. No significant difference was found between LDLT and OLT for the incidence of EBV and CMV infections. In terms of laboratory indexes, the recovery time of PLT, AKP and AST levels were significantly longer for OLT than LDLT. Among different types of metabolic disease, no significant difference was found in viral infection, EAD, laboratory indexes, severe complications or duration of hospital stay.ConclusionsLDLT shows a lower incidence rate of EAD and complications, while it also shows a 1-year survival rate and incidence of viral infections compared similar to that of OLT. LDLT is the better treatment option of pediatric liver transplantation for metabolic liver disease compared with OLT.     

Clinical analysis of emergency liver transplantation: the role of living donor liver transplantation

The current liver allocation system requires reevaluation because of the advancements in peri‐transplantation care and surgical techniques. And, the role of living donor liver transplantation (LDLT) in an emergency has not been determined yet. Retrospective review of all patients undergoing emergency liver transplantation (LT) from January 2000 to June 2010 was conducted, and clinical data were analyzed. Of the total 505 LTs, 69 patients (13.7%) underwent an emergency LT. Of these, 54 patients (78.3%) underwent LDLT using a right liver, and 15 patients (21.7%) underwent deceased donor liver transplantation (DDLT). The overall hospital mortality was 21.7% (15/69). The leading cause of death after transplantation was sepsis (60.0%). Multivariate analysis demonstrated that a model for end‐stage liver disease (MELD) >33 [hazard ratio (HR), 16.6; 95% confidence interval (CI), 1.443–191.632; p = 0.024] and existence of pre‐transplantation intubation (HR, 18.2; 95% CI, 1.463–225.483; p = 0.024) were independent factors associated with poor survival after emergency LT. LDLT group and DDLT group showed no difference in hospital mortality (p = 0.854) and graft survival (p = 0.861). Thus, MELD score and respiratory insufficiency could be parameters predicting post‐transplant survival. And, LDLT using the right liver could be an appropriate alternative to DDLT in an emergency.     

Living donor transplantation of a pelvic kidney

Pelvic kidneys are uncommon anomalies rarely utilized in kidney transplantation. We describe a successful case of living-donor transplantation using a pelvic kidney in a 17-month-old infant with congenital renal dysplasia. The recipient had exhausted all options for renal replacement therapy, and urgent transplantation was considered a life saving treatment.     

Impact of biliary complications in right lobe living donor liver transplantation

Biliary reconstruction is one of the most challenging parts of right lobe living donor liver transplantation (RL LDLT), and biliary complications have been reported as the first source of surgical complications of this procedure. We reviewed biliary reconstruction and complications in 27 consecutive RL LDLTs. We compared the first 14 procedures (group 1) to the last 13 (group 2). Seven patients (25.9%) experienced a biliary complication (five leaks and two strictures). The incidence of biliary complications was 11.1% in RL grafts with a single duct and 55.5% in graft presenting multiple bile ducts (P = 0.03). Four of the 18 patients with a duct-to-duct reconstruction (22.2%) and three of the 11 patients with a Roux-en-Y reconstruction (27.3%) developed a biliary complication (P = ns). The incidence of biliary complications significantly decreased from 42.9% (n = 6) in the first group to 7.6% (n = 1) in the second group (P = 0.05). The overall 1-year graft and patient survival were 57.1% and 64.3% in group 1 versus 100.0% and 100% in group 2 (P = 0.01; P = 0.006). Biliary complications remain one of the most important technical complications affecting RL LDLT. Nevertheless, attention and surgical refinement can lead to a significant reduction of the biliary complication rate, improving graft and patient survival.     

Meta-analysis and meta-regression of outcomes for adult living donor liver transplantation versus deceased donor liver transplantation

Prior single center or registry studies have shown that living donor liver transplantation (LDLT) decreases waitlist mortality and offers superior patient survival over deceased donor liver transplantation (DDLT). The aim of this study was to compare outcomes for adult LDLT and DDLT via systematic review. A meta-analysis was conducted to examine patient survival and graft survival, MELD, waiting time, technical complications, and postoperative infections. Out of 8600 abstracts, 19 international studies comparing adult LDLT and DDLT published between 1/2005 and 12/2017 were included. U.S. outcomes were analyzed using registry data. Overall, 4571 LDLT and 66,826 DDLT patients were examined. LDLT was associated with lower mortality at 1, 3, and 5 years posttransplant (5-year HR 0.87 [95% CI 0.81–0.93], p < .0001), similar graft survival, lower MELD at transplant (p < .04), shorter waiting time (p < .0001), and lower risk of rejection (p = .02), with a higher risk of biliary complications (OR 2.14, p < .0001). No differences were observed in rates of hepatic artery thrombosis. In meta-regression analysis, MELD difference was significantly associated with posttransplant survival (R² 0.56, p = .02). In conclusion, LDLT is associated with improved patient survival, less waiting time, and lower MELD at LT, despite posing a higher risk of biliary complications that did not affect survival posttransplant.