Warm ischemia time and elevated serum uric acid are associated with metabolic syndrome after liver transplantation with donation after cardiac death

AIM To describe the prevalence of posttransplant metabolic syndrome(PTMS) after donation after cardiac death(DCD) liver transplantation(LT) and the pre-and postoperative risk factors.METHODS One hundred and forty-seven subjects who underwent DCD LT from January 2012 to February 2016 were enrolled in this study. The demographics and the clinical characteristics of pre-and post-transplantation were collected for both recipients and donors. PTMS was defined according to the 2004 Adult Treatment Panel-Ⅲ criteria. All subjects were followed monthly for the initial 6 mo after discharge, and then, every 3 mo for 2 years. The subjects were followed every 6 mo or as required after 2 years post-LT.RESULTS The prevalence of PTMS after DCD donor orthotopic LT was 20/147(13.6%). Recipient's body mass index(P = 0.024), warm ischemia time(WIT)(P = 0.045), and posttransplant hyperuricemia(P = 0.001) were significantly associated with PTMS. The change in serum uric acid levels in PTMS patients was significantly higher than that in non-PTMS patients(P 0.001). After the 1 s t mo, the level of serum uric acid of PTMS patients rose continually over a period, while it was unaltered in non-PTMS patients. After transplantation, the level of serum uric acid in PTMS patients was not associated with renal function.CONCLUSION PTMS could occur at early stage after DCD LT with growing morbidity with the passage of time. WIT and post-LT hyperuricemia are associated with the prevalence of PTMS. An increased serum uric acid level is highly associated with PTMS and could act as a serum marker in this disease.     

Normothermic regional perfusion vs. super-rapid recovery in controlled donation after circulatory death liver transplantation

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我国心脏死亡器官捐献供肝现状及其肝移植的临床进展

肝移植是治疗终末期肝病的重要手段,但是供体短缺的问题日益显现,因此适合我国国情,同时符合国际标准的心脏死亡器官捐献(DCD)应该是现阶段缓解器官短缺的一种重要手段。本文回顾了国际上DCD肝移植的曲折发展历程,通过对DCD肝移植的定义与分类、伦理原则、适应证、获取方案、捐献情况和临床效果进行综述,认为DCD供肝是目前我国肝移植供体极度短缺大环境下的一支"生力军"。随着其工作的深入开展,必将成为我国肝移植的重要组成部分。     

Donor preoperative oxygen delivery and post-extubation hypoxia impact donation after circulatory death hypoxic cholangiopathy

AIM: To evaluate donation after circulatory death(DCD) orthotopic liver transplant outcomes [hypoxic cholangiopathy(HC) and patient/graft survival] and donor risk-conditions.METHODS: From 2003-2013, 45 DCD donor transplants were performed. Predonation physiologic data from UNOS Donor Net included preoperative systolic and diastolic blood pressure, heart rate, p H, SpO_2, PaO_2, FiO_2, and hemoglobin. Mean arterial bloodpressure was computed from the systolic and diastolic blood pressures. Donor preoperative arterial O_2 content was computed as [hemoglobin(gm/d L) × 1.37(m L O_2/gm) × SpO_2%) +(0.003 × PaO_2)]. The amount of preoperative donor red blood cell transfusions given and vasopressor use during the intensive care unit stay were documented. Donors who were transfused ≥ 1 unit of red-cells or received ≥ 2 vasopressors in the preoperative period were categorized as the red-cell/multi-pressor group. Following withdrawal of life support, donor ischemia time was computed as the number-of-minutes from onset of diastolic blood pressure 60 mm Hg until aortic cross clamping. Donor hypoxemia time was the number-of-minutes from onset of pulse oximetry 80% until clamping. Donor hypoxia score was(ischemia time + hypoxemia time) ÷ donor preoperative hemoglobin.RESULTS: The 1, 3, and 5 year graft and patient survival rates were 83%, 77%, 60%; and 92%, 84%, and 72%, respectively. HC occurred in 49% with 16% requiring retransplant. HC occurred in donors with increased age(33.0 ± 10.6 years vs 25.6 ± 8.4 years, P = 0.014), less preoperative multiple vasopressors or red-cell transfusion(9.5% vs 54.6%, P = 0.002), lower preoperative hemoglobin(10.7 ± 2.2 gm/d L vs 12.3 ± 2.1 gm/d L, P = 0.017), lower preoperative arterial oxygen content(14.8 ± 2.8 m L O_2/100 m L blood vs 16.8 ± 3.3 m L O_2/100 m L blood, P = 0.049), greater hypoxia score 2.0(69.6% vs 25.0%, P = 0.006), and increased preoperative mean arterial pressure(92.7 ± 16.2 mm Hg vs 83.8 ± 18.5 mm Hg, P = 0.10). HC was independently associated with age, multi-pressor/redcell transfusion status, arterial oxygen content, hypoxia score, and mean arterial pressure(r~2 = 0.6197). The transplantation rate was greater for the later period with more liberal donor selection [era 2(7.1/year)], compared to our early experience [era 1(2.5/year)]. HC occurred in 63.0% during era 2 and in 29.4% during era 1(P = 0.03). Era 2 donors had longer times for extubation-to-asystole(14.4 ± 4.7 m vs 9.3 ± 4.5 m, P = 0.001), ischemia(13.9 ± 5.9 m vs 9.7 ± 5.6 m, P = 0.03), and hypoxemia(16.0 ± 5.1 m vs 11.1 ± 6.7 m, P = 0.013) and a higher hypoxia score 2.0 rate(73.1% vs 28.6%, P = 0.006).CONCLUSION: Easily measured donor indices, including a hypoxia score, provide an objective measure of DCD liver transplantation risk for recipient HC. Donor selection criteria influence HC rates.     

Comparing outcomes of donation after cardiac death versus donation after brain death in liver transplant recipients with hepatitis C: A systematic review and meta-analysis

BACKGROUND:

Liver transplantation (LT) using organs donated after cardiac death (DCD) is increasing due, in large part, to a shortage of organs. The outcome of using DCD organs in recipients with hepatits C virus (HCV) infection remains unclear due to the limited experience and number of publications addressing this issue.

OBJECTIVE:

To evaluate the clinical outcomes of DCD versus donation after brain death (DBD) in HCV-positive patients undergoing LT.

METHODS:

Studies comparing DCD versus DBD LT in HCV-positive patients were identified based on systematic searches of seven electronic databases and multiple sources of gray literature.

RESULTS:

The search identified 58 citations, including three studies, with 324 patients meeting eligibility criteria. The use of DCD livers was associated with a significantly higher risk of primary nonfunction (RR 5.49 [95% CI 1.53 to 19.64]; P=0.009; I²=0%), while not associated with a significantly different patient survival (RR 0.89 [95% CI 0.37 to 2.11]; P=0.79; I²=51%), graft survival (RR 0.40 [95% CI 0.14 to 1.11]; P=0.08; I²=34%), rate of recurrence of severe HCV infection (RR 2.74 [95% CI 0.36 to 20.92]; P=0.33; I²=84%), retransplantation or liver disease-related death (RR 1.79 [95% CI 0.66 to 4.84]; P=0.25; I²=44%), and biliary complications.

CONCLUSIONS:

While the literature and quality of studies assessing DCD versus DBD grafts are limited, there was significantly more primary nonfunction and a trend toward decreased graft survival, but no significant difference in biliary complications or recipient mortality rates between DCD and DBD LT in patients with HCV infection. There is insufficient literature on the topic to draw any definitive conclusions.     

Outcomes of DCD liver transplantation using organs treated by hypothermic oxygenated perfusion before implantation

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Endoscopic management of biliary complications after orthotopic liver transplantation

BACKGROUND: Biliary complications are a serious problem in patients after liver transplantation and often require reoperation. This study was conducted to summarize the endoscopic diagnosis and management of biliary complications after orthotopic liver transplantation (OLT). METHODS: From December 2000 to November 2003, twelve endoscopic retrograde cholangiopancreatographies(ERCPs) were performed in 7 patients after OLT at Digestive Endoscopic Center of Changhai Hospital in Shanghai, China. The therapeutic maneuvers included endoscopic sphincterotomy (EST), biliary stent placement, balloon and basket extraction, irrigation, and nasobiliary tube placement. A retrospective study was made to determine the types of biliary tract complications after OLT. The success of ERCP and therapeutic maneuvers was also evaluated. RESULTS: Biliary tract complications including biliary stricture, biliary leak, biliary sludge, and stump leak of the cyst duct were treated respectively by endoscopic sphincterotomy with sludge extraction, stricture dilation or endoscopic retrograde biliary drainage. Two of the 3 patients with proximal common bile duct stricture were successfully treated with ERCP and stent placement. Four patients with anastomotic stricture and/without bile leak were treated successfully by dilation and stent placement or endoscopic nosobiliary drainage. No severe ERCP-related complications occurred. CONCLUSIONS: ERCP is an effective and accurate approach for the diagnosis of biliary tract complications after OLT, and placement of a stent is a safe initial treatment for biliary complications after liver transplantation.     

Prediction of rat liver transplantation outcomes using energy metabolites measured by microdialysis

Background: Warm ischemia jeopardizes graft quality and recipient survival in donation after cardiac death(DCD) transplantation. Currently, there is no system to objectively evaluate the liver quality from DCD. The present study tried to use energy metabolites to evaluate the donor liver quality. Methods: We divided 195 Sprague-Dawley rats into five groups: the control( n = 39), warm ischemic time(WIT) 15 min( n = 39), WIT 30 min( n = 39), WIT 45 min( n = 39), and WIT 60 min( n = 39) groups. Three rats from each group were randomly selected for pretransplant histologic evaluation of warm ischemiarelated damage. The remaining 36 rats were randomly divided into donors and recipients of 18 liver transplantations, and were subjected to postoperative liver function and survival analyses. Between cardiac arrest and cold storage, liver energy metabolites including glucose, lactate, pyruvate, and glycerol were measured by microdialysis. The lactate to pyruvate ratio(LPR) was calculated. Results: The changes in preoperative pathology with warm ischemia were inconspicuous, but the trends in postoperative pathology and aminotransferase levels were consistent with preoperative energy metabolite measurements. The 30-day survival rates of the control and WIT 15, 30, 45, and 60 min groups were 100%, 81.82%, 76.92%, 58.33%, and 25.00%, respectively. The areas under the receiver operating characteristic curves of glucose, lactate, glycerol, and LPR were 0.87, 0.88, 0.88, and 0.92, respectively. Conclusion: Glucose, lactate, glycerol, and LPR are predictors of graft quality and survival outcomes in DCD transplantation.     

Outcomes following liver transplantation from HCV-seropositive donors to HCV-seronegative recipients

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Donation after circulatory death donors in lung transplantation

Transplantation of any organ into a recipient requires a donor. Lung transplant has a long history of an inadequate number of suitable donors to meet demand, leading to deaths on the waiting list annually since national data was collected, and strict listing criteria. Before the Uniform Determination of Death Act (UDDA), passed in 1980, legally defined brain death in the U.S., all donors for lung transplant came from sudden death victims [uncontrolled Donation after Circulatory Death donors (uDCDs)] in the recipient’s hospital emergency department. After passage of the UDDA, uDCDs were abandoned to Donation after Brain Death donors (DBDs)—perhaps prematurely. Compared to livers and kidneys, many DBDs have lungs that are unsuitable for transplant, due to aspiration pneumonia, neurogenic pulmonary edema, trauma, and the effects of brain death on lung function. Another group of donors has become available—patients with a devastating irrecoverable brain injury that do not meet criteria for brain death. If a decision is made by next-of-kin (NOK) to withdraw life support and allow death to occur by asphyxiation, with NOK consent, these individuals can have organs recovered if death occurs relatively quickly after cessation of mechanical ventilation and maintenance of their airway. These are known as controlled Donation after Circulatory Death donors (cDCDs). For a variety of reasons, in the U.S., lungs are recovered from cDCDs at a much lower rate than kidneys and livers. Ex-vivo lung perfusion (EVLP) in the last decade has had a modest impact on increasing the number of lungs for transplant from DBDs, but may have had a larger impact on lungs from cDCDs, and may be indispensable for safe transplantation of lungs from uDCDs. In the next decade, DCDs may have a substantial impact on the number of lung transplants performed in the U.S. and around the world.     

Endoscopic management of biliary strictures after liver transplantation

Bile duct strictures remain a major source of morbidity after orthotopic liver transplantation （OLT）. Biliary strictures are classified as anastomotic or non-anastomotic strictures according to location and are defined by distinct clinical behaviors. Anastomotic strictures are localized and short. The outcome of endoscopic treatment for anastomotic strictures is excellent. Nonanastomotic strictures often result from ischemic and immunological events, occur earlier and are usually multiple and longer. They are characterized by a far less favorable response to endoscopic management, higher recurrence rates, graft loss and need for retransplantation. Living donor OLT patients present a unique set of challenges arising from technical factors, and stricture risk for both recipients and donors. Endoscopic treatment of living donor OLT patients is less promising. Current endoscopic strategies for biliary strictures after OLT include repeated balloon dilations and placement of multiple side-by-side plastic stents. Lifelong surveillance is required in all types of strictures. Despite improvements in incidence and long term outcomes with endoscopic management, and a reduced need for surgical treatment, the impact of strictures on patients after OLT is significant. Future considerations include new endoscopic technologies and improved stents, which could potentially allow for a decreased number of interventions, increased intervals before retreatment, and decreased reliance on percutaneous and surgical modalities. Thisreview focuses on the role of endoscopy in biliary strictures, one of the most common biliary complications after OLT.     

Aetiology and risk factors of ischaemic cholangiopathy after liver transplantation

Liver transplantation (LT) is the best treatment for end-stage hepatic failure, with an excellent survival rates over the last decade. Biliary complications after LT pose a major challenge especially with the increasing number of procured organs after circulatory death. Ischaemic cholangiopathy (IC) is a set of disorders characterized by multiple diffuse strictures affecting the graft biliary system in the absence of hepatic artery thrombosis or stenosis. It commonly presents with cholestasis and cholangitis resulting in higher readmission rates, longer length of stay, repeated therapeutic interventions, and eventually re-transplantation with consequent effects on the patient’s quality of life and increased health care costs. The pathogenesis of IC is unclear and exhibits a higher prevalence with prolonged ischaemia time, donation after circulatory death (DCD), rejection, and cytomegalovirus infection. The majority of IC occurs within 12 mo after LT. Prolonged warm ischaemic times predispose to a profound injury with a subsequently higher prevalence of IC. Biliary complications and IC rates are between 16% and 29% in DCD grafts compared to between 3% and 17% in donation after brain death (DBD) grafts. The majority of ischaemic biliary lesions occur within 30 d in DCD compared to 90 d in DBD grafts following transplantation. However, there are many other risk factors for IC that should be considered. The benefits of DCD in expanding the donor pool are hindered by the higher incidence of IC with increased rates of re-transplantation. Careful donor selection and procurement might help to optimize the utilization of DCD grafts.     

Minimising cold ischaemic time is essential in cardiac death donor-associated liver transplantation

Background

An important issue in the transplantation of livers procured from cardiac death donors (CDDs) concerns why some centres report equivalent outcomes and others report inferior outcomes in transplantations using CDD organs compared with standard criteria donor (SCD) organs. Resolving this discrepancy may increase the number of usable organs.

Objectives

This study aimed to test whether differences in cold ischaemic time (CIT) are critical during CDD organ transplantation and whether such differences might explain the disparate outcomes.

Methods

Results of CDD liver transplants in our own centre were compared retrospectively with results in a matched cohort of SCD liver recipients. Endpoints of primary non-function (PNF) and ischaemic cholangiopathy (IC) were used because these outcomes are clearly associated with CDD organ use.

Results

In 22 CDD organ transplants, CIT was a strong predictor of PNF or IC (P = 0.021). Minimising CIT in CDD organ transplants produced outcomes similar to those in a matched SCD organ transplant cohort at our centre and in SCD organ transplant results nationally (1- and 3-year graft and patient survival rates: 90.9% and 73.3% vs. 77.6% and 69.2% in CDD and SCD grafts, respectively. A review of the published literature demonstrated that centres with higher CITs tend to have higher rates of PNF or IC (correlation coefficient: 0.41).

Conclusions

These findings suggest that a targeted effort to minimise CIT might improve outcomes and allow the safer use of CDD organs.     

Lung transplantation from donors after circulatory death using portable ex vivo lung perfusion

BACKGROUND:

Donation after circulatory death is a novel method of increasing the number of donor lungs available for transplantation. Using organs from donors after circulatory death has the potential to increase the number of transplants performed.

METHODS:

Three bilateral lung transplants from donors after circulatory death were performed over a six-month period. Following organ retrieval, all sets of lungs were placed on a portable ex vivo lung perfusion device for evaluation and preservation.

RESULTS:

Lung function remained stable during portable ex vivo perfusion, with improvement in partial pressure of oxygen/fraction of inspired oxygen ratios. Mechanical ventilation was discontinued within 48 h for each recipient and no patient stayed in the intensive care unit longer than eight days. There was no postgraft dysfunction at 72 h in two of the three recipients. Ninety-day mortality for all recipients was 0% and all maintain excellent forced expiratory volume in 1 s and forced vital capacity values post-transplantation.

CONCLUSION:

The authors report excellent results with their initial experience using donors after circulatory death after portable ex vivo lung perfusion. It is hoped this will allow for the most efficient use of available donor lungs, leading to more transplants and fewer deaths for potential recipients on wait lists.     

Endoscopic management of biliary complications after liver transplantation

Biliary complications are common in liver transplant recipients and may develop in up to one-third of all patients. Bile leaks generally occur within the first 3 months and are frequently related to T-tube removal. The recent trend to avoid of T-tubes has probably resulted in a reduced incidence of such bile leaks. The other major biliary complications in liver transplant recipients include biliary strictures, choledocholithiasis, biliary casts and sphincter of Oddi dysfunction. Biliary strictures can be classified into anastomotic and non-anastomotic strictures. Anastomotic strictures are generally related to technical complications of choledochocholedochostomy, while non-anastomotic strictures are frequently related to hepatic artery thrombosis. The overwhelming majority of biliary complications choledochocholedochostomy can be managed by endoscopic means, ranging from use of plastic stents, balloon dilation or endoscopic sphincteromoty. Surgical revision may be required in rare instances such as recurrent biliary casts or large caliber leaks associated with anastomotic strictures. The purpose of this review is to review the incidence, risk factors for and pathogenesis of biliary complications after liver transplantation. The results of endoscopic management of these strictures is also described in detail and should be of interest to therapeutic endoscopists, liver transplant physicians, transplant surgeons and therapeutic endoscopists.     

肝移植术后胆道吻合口狭窄内镜处理策略

目的探讨肝移植术后胆道吻合口狭窄的内镜处理和操作技巧。方法分析第二军医大学附属东方肝胆外科医院内镜科2003年12月至2006年12月经十二指肠镜治疗的228例肝移植患者临床资料。结果肝移植术后胆道并发症患者中,合并或单纯胆道吻合口病变者187例,占82.0%,其中175例成功进行了内镜下治疗,成功率93.6%。187例有胆道吻合口病变的患者中,吻合口狭窄149例(79.7%),其中成功进行内镜下逆行胰胆管造影(ERCP)治疗者145例,成功率为97.3%。结论肝移植后胆道并发症患者中,合并或单纯胆道吻合口狭窄者占绝大多数,ERCP是诊断和治疗肝移植术后胆道并发症的首选方法之一。行ERCP时导丝及其他附件通过胆道吻合口狭窄的操作技巧是治疗成功的关键。     

Causes and consequences of ischemic-type biliary lesions after liver transplantation

Biliary complications are a major source of morbidity, graft loss, and even mortality after liver transplantation. The most troublesome are the so-called ischemic-type biliary lesions (ITBL), with an incidence varying between 5% and 15%. ITBL is a radiological diagnosis, characterized by intrahepatic strictures and dilatations on a cholangiogram, in the absence of hepatic artery thrombosis. Several risk factors for ITBL have been identified, strongly suggesting a multifactorial origin. The main categories of risk factors for ITBL include ischemia-related injury; immunologically induced injury; and cytotoxic injury, induced by bile salts. However, in many cases no specific risk factor can be identified. Ischemia-related injury comprises prolonged ischemic times and disturbance in blood flow through the peribiliary vascular plexus. Immunological injury is assumed to be a risk factor based on the relationship of ITBL with ABO incompatibility, polymorphism in genes coding for chemokines, and pre-existing immunologically mediated diseases such as primary sclerosing cholangitis and autoimmune hepatitis. The clinical presentation of patients with ITBL is often not specific; symptoms may include fever, abdominal complaints, and increased cholestasis on liver function tests. Diagnosis is made by imaging studies of the bile ducts. Treatment starts with relieving the symptoms of cholestasis and dilatation by endoscopic retrograde cholangiopancreaticography (ERCP) or percutaneous transhepatic cholangiodrainage (PTCD), followed by stenting if possible. Eventually up to 50% of the patients with ITBL will require a retransplantation or may die. In selected patients, a retransplantation can be avoided or delayed by resection of the extra-hepatic bile ducts and construction of a hepaticojejunostomy. More research on the pathogenesis of ITBL is needed before more specific preventive or therapeutic strategies can be developed.     

Endoscopic treatment of biliary complications after right-lobe living-donor liver transplantation with duct-to-duct biliary anastomosis

Background/Purpose

The aims of this study were to characterize the features of the biliary complications that occur after right-lobe living-donor liver transplantation (RL-LDLT) with duct-to-duct biliary anastomosis, and to evaluate the efficacy of treating biliary complications endoscopically.

Methods

The records of 273 consecutive patients who underwent RL-LDLT with duct-to-duct biliary anastomosis from July 1999 through July 2005 at Kyoto University Hospital were reviewed to determine the overall incidence of postoperative biliary complications and the outcome of endoscopic repair of those complications.

Results

Biliary complications occurred in 93 (34.1%) of the patients. These complications were: 80 biliary strictures (75 anastomotic and 5 nonanastomotic) and 16 biliary leakages (5 patients with biliary leakage also had a biliary stricture); most (72%) of the anastomotic strictures were complex (i.e., fork-shaped or trident-shaped). The strictures and leakages were repaired by the endoscopic placement of multiple inside stents above the sphincter of Oddi, and by nasobiliary drainage, respectively. The procedure was successful in repairing 51 (68.0%) of the anastomotic strictures and 8 (50.0%) of the biliary leakages.

Conclusions

Endoscopic stenting of the bile ducts is efficacious in treating biliary complications related to RL-LDLT with duct-to-duct biliary anastomosis and the stenting should be attempted before surgical revision of strictures and leakages.     

体外膜肺氧合技术对脑心双死亡器官捐献供肝的保护作用

目的探讨体外膜肺氧合(ECMO)技术在公民逝世器官捐献供肝保护中的应用,总结ECMO技术保护供肝的初步体会及经验。方法收集江西省人民医院2015年1月-2018年12月运用ECMO技术完成脑心双死亡器官捐献(DBCD)肝移植供者/受者及常规DBCD肝移植供者/受者的临床资料,对供肝的保护及移植效果进行对比分析。计量资料两组间比较采用t检验;计数资料两组间比较采用χ2检验。结果共纳入一般情况及肝功能接近的供者32例,根据采用的方法将其分为对照组(常规DBCD肝移植)和研究组(运用ECMO技术完成DBCD肝移植),每组各16例;32例肝移植受者分为对应的对照组(n=16)和研究组(n=16)。器官获取前供者对照组与供者研究组比较,心率、收缩压、舒张压、血氧分压、乳酸水平、中心静脉压、TBil、ALT、AST差异均有统计学意义(t值分别为14.121、-17.817、-19.187、-8.927、4.559、-3.495、3.357、4.111、3.553,P值均<0.05)。与受者对照组术后第7天肝功能相比,受者研究组肝移植术后肝功能恢复速度更快,两组TBil、DBil、ALT、AST、ALP、GGT比较,差异均有统计学意义(t值分别为9.309、4.783、5.067、2.203、4.774、5.257,P值均<0.05);受者研究组患者住院时间明显缩短[(12.65±2.86)d vs(20.87±4.98)d,t=5.756,P<0.001]。结论运用ECMO技术获取并实施肝移植临床效果较好,科学合理运用ECMO技术可以有效改善供肝质量,对我国公民逝世器官捐献工作有着积极的作用。