活体肝移植进展与展望（2000-2020）

活体肝移植比公民逝世后器官捐献肝移植操作更为复杂，围手术期评估及技术实施直接影响供体安全和受体预后。目前，行活体肝移植时，供体选择应遵循“自愿、知情、无害”伦理原则，利用影像学评估供肝质量、解剖结构及残肝体积；受体选择时优先考虑良性终末期肝病病人，而选择肝癌病人应考虑肿瘤分期；移植物选择应满足不同受体的“移植物-受体重量比”标准，对于<3岁的儿童，其比值在2%~4%为宜；在传统开放手术供肝获取经验基础上，腹腔镜供肝获取技术发展与挑战并存；术中各管道重建时，管道条件、匹配程度及通畅性是移植技术的关键；供受体血型不相容时，应用利妥昔单抗可起到减少并发症及改善预后作用；术后精细化管理，尽量减少免疫抑制剂用量以期减少其药物相关副反应。尽管存在诸多问题，相信随着外科技术的进步，医生对肝脏解剖认识的加深及移植物再生血流动力学的理解，活体肝移植技术会更加完备、更加安全。作为公民逝世后器官捐献肝移植的重要补充，活体肝移植将为更多终末期肝病病人提供有效治疗手段。     

Perioperative synbiotic treatment to prevent infectious complications in patients after elective living donor liver transplantation: a prospective randomized study

Background

Although the effect of synbiotic therapy using prebiotics and probiotics has been reported in hepatobiliary surgery, there are no reports of the effect on elective living-donor liver transplantation (LDLT).

Methods

Fifty adult patients undergoing LDLT between September 2005 and June 2009 were randomized into a group receiving 2 days of preoperative and 2 weeks of postoperative synbiotic therapy (Bifidobacterium breve, Lactobacillus casei, and galactooligosaccharides [the BLO group]) and a group without synbiotic therapy (the control group). Postoperative infectious complications were recorded as well as fecal microflora before and after LDLT in each group.

Results

Only 1 systemic infection occurred in the BLO group (4%), whereas the control group showed 6 infectious complications (24%), with 3 cases of sepsis and 3 urinary tract infections with Enterococcus spp (P = .033 vs BLO group). No other type of complication showed any difference between the groups.

Conclusions

Infectious complications after elective LDLT significantly decreased with the perioperative administration of synbiotic therapy.     

Hepatic IL-8 release during graft procurement is associated with impaired graft function after human liver transplantation

Ilmakunnas M, Höckerstedt K, Mäkisalo H, Siitonen S, Repo H, Pesonen EJ. Hepatic IL-8 release during graft procurement is associated with impaired graft function after human liver transplantation.
Clin Transplant 2010: 24: 29–35. © 2009 John Wiley & Sons A/S.
Abstract:  In experimental models, brain death induces inflammatory cascades, leading to reduced graft survival. Thus far, factors prior to graft preservation have gained less attention in clinical setting. We studied pre-preservation inflammatory response and its effects on graft function in 30 brain dead liver donors and the respective recipients. Before donor graft perfusion, portal and hepatic venous blood samples were drawn for phagocyte adhesion molecule expression and plasma cytokine determinations. Donor intensive care unit stay correlated with donor C-reactive protein ( R  =   0.472, p   =   0.013) and IL-6 ( R  =   0.419, p   =   0.026) levels, and donor ( R  =   0.478, p   =   0.016) and recipient gamma-glutamyl transferase ( R  =   0.432, p   =   0.019) levels. During graft procurement, hepatic IL-8 release was observed in 17/30 donors. Grafts with hepatic IL-8 release exhibited subsequently higher alkaline phosphatase [319 (213–405) IU/L vs. 175 (149–208) IU/L, p   =   0.006] and bilirubin [101 (44–139) μmol/L vs. 30 (23–72) μmol/L, p   =   0.029] levels after transplantation. Our findings support the concept that inflammatory response in the brain dead organ donor contributes to the development of graft injury in human liver transplantation.     

儿童活体肝移植受者术后新发乙型肝炎病毒感染的临床研究

目的  探讨儿童活体肝移植术后新发乙型肝炎病毒(HBV)感染的临床特点及其防治策略。方法  2010年7月至2014年7月, 在首都医科大学附属北京友谊医院移植中心和天津一中心医院器官移植中心接受活体肝移植术的106例儿童受者纳入本研究, 所有手术由同一外科团队完成。根据供者术前HBV血清学标志物的结果, 将儿童受者分为供肝乙型肝炎核心抗体(抗-HBc)阳性组(45例)和供肝抗-HBc阴性组(61例)。了解两组儿童受者的新发HBV感染情况, 分析供肝抗-HBc阳性组儿童受者新发HBV感染的危险因素, 了解新发HBV感染患儿的特征。结果  供肝抗-HBc阳性组和阴性组新发HBV感染发生率分别为18%(8/45)和2%(1/61)。受者术前抗-HBs阴性、术后无抗病毒治疗是抗-HBc阳性供肝受者新发HBV感染的危险因素(均为P < 0.05)。发病距移植手术的中位数时间12个月(8~48个月)。9例儿童受者中, 接受拉米夫定治疗7例, 未予抗病毒治疗2例, 均全部存活。结论  应用抗-HBc阳性供肝的儿童肝移植受者, 其术后存在感染HBV的风险。受者术前抗-HBs阴性、术后未给予预防性核苷类似物治疗是抗-HBc阳性供肝受者新发HBV感染的危险因素。接受供体抗-HBc阳性的肝移植儿童受体应使用核苷类似物预防新发HBV感染, 移植术前亦要加强对其接种乙肝疫苗。     

A prospective study on the effect of recipient nutritional status on outcome in liver transplantation

In a prospective study, we have examined the effect of nutritional status, using anthropometric measurement, on outcome in 102 consecutive adult patients undergoing elective orthotopic liver transplantation. Mid-arm muscle circumference was calculated from these two measurements. Patient outcome variables were time spent in the intensive therapy unit, total time in hospital, infective complications and mortality within 6 months. Graft outcome variables were early graft function, peak aspartate transaminase, alkaline phosphatase, bilirubin and prothrombin time. Group A patients were below and group B patients above the 25th percentile for mid-arm circumference and triceps skin fold thickness. Eighty-four patients (79 %) were at or below the 25th percentile of anthropometric measurements and 30 patients (28 %) were below the 5th percentile. The median mid-arm muscle circumference in group A was 22.3 (range 16.4–28.9) cm and 25.7 (range 21.7–31.8) cm in group B. The medial albumin level was similar in the two groups. There were significantly more bacterial infections in group A (27/84, 32 %) than in group B (2/22, 8 %; χ2 = 5.4, P = 0.02). There was a difference in mortality up to 6 months post-operatively that failed to reach statistical significance (Wilcoxon-Gehan statistic –199, P = 0.09). There were 11/84 (13 %) deaths in group A and no deaths in group B (χ ² = 2.8, P = 0.09). Post transplantation, there were significant differences (Kruskal-Wallis Anova) between groups A and B for peak alkaline phosphatase (683 vs 334 IU/I, P = 0.05) and peak prothrombin time [16 (range 13–25) vs 19.5 (range 12–65), P = 0.03]. These data suggest that a significant proportion of patients undergoing liver transplantation are nutritionally compromised and that this has effects on patient infection, susceptibility, graft function and mortality, which may possibly be improved by nutritional intervention. Received: 6 February 1997 Received after revision: 7 May 1997 Accepted: 5 June 1997     

Frailty phenotypes and mortality after lung transplantation: A prospective cohort study

Frailty is associated with increased mortality among lung transplant candidates. We sought to determine the association between frailty, as measured by the Short Physical Performance Battery (SPPB), and mortality after lung transplantation. In a multicenter prospective cohort study of adults who underwent lung transplantation, preoperative frailty was assessed with the SPPB (n = 318) and, in a secondary analysis, the Fried Frailty Phenotype (FFP; n = 299). We tested the association between preoperative frailty and mortality following lung transplantation with propensity score–adjusted Cox models. We calculated postestimation marginalized standardized risks for 1‐year mortality by frailty status using multivariate logistic regression. SPPB frailty was associated with an increased risk of both 1‐ and 4‐year mortality (adjusted hazard ratio [aHR]: 7.5; 95% confidence interval [CI]: 1.6‐36.0 and aHR 3.8; 95%CI: 1.8‐8.0, respectively). Each 1‐point worsening in SPPB was associated with a 20% increased risk of death (aHR: 1.20; 95%CI: 1.08‐1.33). Frail subjects had an absolute increased risk of death within the first year after transplantation of 12.2% (95%CI: 3.1%‐21%). In secondary analyses, FFP frailty was associated with increased risk of death within the first postoperative year (aHR: 3.8; 95%CI: 1.1‐13.2) but not over longer follow‐up. Preoperative frailty is associated with an increased risk of death after lung transplantation.     

Abdominal emergencies after liver transplantation: Presentation and surgical management

With an increasing number of liver transplantation (LT) and an enhanced overall survival, LT recipients are more likely to be admitted in emergency departments of general hospitals. Yet, in LT recipients, common but also benign symptoms may reveal a LT‐related (or not) severe condition. To improve management of LT recipients by emergency physicians and general surgeons and potentially improve long‐term outcomes, a clinical review was performed. Overall, CT scan and blood tests should be systematically performed. Immunosuppressive side effects should be excluded using blood tests. LT‐related complications are more likely to occur during the first three months after LT, including mainly bile leak, arterial aneurysm, and pseudoaneurysm. Patients should be referred in emergency to tertiary centers. Non‐LT‐related complications and common abdominal conditions may also be diagnosed in LT recipients. Except in case of diffuse peritonitis or in hemodynamically unstable patients when surgical procedure should be performed, most conditions should be reassessed regarding the immunosuppressive treatment and the adhesive abdominal cavity.     

Living-donor liver transplantation in the new decade: perspective from the twentieth to the twenty-first century

Liver transplantation from living donors developed rapidly in the last decade of the twentieth century and is now an important option in the treatment of patients with end stage and/or irreversible liver diseases. Although the disadvantages of small-for-size grafts are being significantly mitigated by the repertoire of left lobe, while left liver, and right lobe grafts, the struggle for graft size matching has disclosed not a few problems, such as small grafts for advanced disease, anatomical variations in donor livers, and, above all, the increasing importance of donor safety. The range of donor candidates is also an important point of discussion in regard to the social significance of this treatment modality. Apart from the surgical aspects, many medical aspects, including the indications and timing of transplantation specific to this technique, the prevention of disease transmission in family members, and immunological aspects, including the risk of graft-versus-host disease, remain to be clarified. Social and economic questions, as well as surgical and medical issues, will be the theme in the second decade, and the new century, of this newborn treatment modality. Received: January 9, 2001 / Accepted: April 24, 2001     

Perioperative factors influencing patient outcome after liver transplantation

Abstract We have previously shown that the development of multiple organ dysfunction syndrome (MODS) after liver transplantation significantly reduced patient survival. Therefore, the question arises of which are the most prominent perioperative donor and recipient factors leading to MODS after transplantation. In total, 634 patients with 700 liver transplants were analyzed. Donor factors included age, increase in transaminases, sex mismatch, requirement for catecholamines, intensive care time, histology, and macroscopic graft appearence. Recipient factors included Child classification, preoperative gastrointestinal (GI) bleeding, mechanical ventilation, hemodialysis, and requirement for catecholamines. MODS was defined by more than two severe organ dysfunctions. The cumulative 2 to 9‐year patient survival was 90.9 % in patients developing less than 3 severe organ dysfunctions following transplantation. Survival decreased to 60.3 % in patients with MODS. Neither any of the donor factors nor the duration of cold ischemia (CIT) was associated with an increase in MODS or decrease in survival. On the other hand, duration of warm ischemia, amount of blood loss, requirement for red packed blood cells, and reoperation had an influence on the development of MODS (40%‐56%) and decreased patient survival to 58%‐69%. Preoperative therapy with catecholamines, GI bleeding, mechanical ventilation, and hemodialysis were associated with the development of MODS in 54 %‐88 %. Patient survival following MODS decreased to 50%‐74%. Initial graft function had a slight influence on the development of MODS, but no influence on the long‐term patient survival. In conclusion, patient survival was significantly influenced by the development of postoperative MODS. The most prominent factors in this were recipient and intraoperative ones. No major influence was observed for donor factors, CIT, and initial graft function. Prevention of MODS will further improve the outcome after liver transplantation.     

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.     

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.     

Functional portal flow competition after auxiliary partial orthotopic living donor liver transplantation in noncirrhotic metabolic liver disease

Auxilliary partial orthotopic liver transplantation (APOLT) was introduced initially as a tentative or permanent support for patients with potentially reversible fulminant hepatic failure and has extended its indication to congenital metabolic disorder of the liver that has otherwise normal functional integrity. Postoperative management of APOLT is complicated because of functional portal flow competition between the native and graft liver. The native portal vein diversion to the graft is sometimes indicated to prevent functional competition; however, it is still an open question whether this technique can be theoretically indicated for APOLT patients. The authors report a on patient with ornithine transcarbamylase deficiency who received APOLT from a living donor without native portal vein diversion. Because of functional portal vein competition between the native and graft liver, the patient had to have portal vein diversion, portal vein embolization, and finally native hepatectomy to induce the graft regeneration after APOLT. After the experience of the current case, primary portal vein diversion for APOLT with noncirrhotic metabolic liver disease patients to prevent functional portal flow competition is recommended.     

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.     

Risk factors for acute rejection in living donor liver transplantation

The influence of human leukocyte antigen (HLA) compatibility and lymphocytotoxic crossmatch on acute rejection in living donor liver transplantation (LDLT) has not been well examined. We analyzed 100 consecutive adult LDLT cases. The patient and graft survival rates and post-operative complications were assessed. The relation between the incidence of acute rejection and some clinical factors including HLA and lymphocytotoxic matching was also examined. Patients with HLA DR zero mismatching (p = 0.02) or negative T-lymphocytotoxic crossmatch (p = 0.04) had a significantly lower chance of rejection within 6 wk after LDLT. However the results had no influence on the patient survival. Our results demonstrate that in LDLT, a graft from an HLA-DR zero mismatching or negative T-lymphocytotoxic crossmatch might be advantageous because of the decreased probability of early acute rejection.     

Long‐term impact and clinical significance of living donor liver transplantation with respect to donor liver restoration and spleen size: A prospective study

This study aimed to evaluate postoperative long‐term liver restoration and splenic enlargement and their clinical significance in living donor liver transplantation. One hundred and sixteen donors who had donated livers more than 5 years previously accepted the invitation to participate in this study. The liver restoration rate and the splenic enlargement rate were calculated as the rate with respect to the original volume. The mean liver restoration rate was 0.99 ± 0.12 and older age was associated with a higher incidence for liver restoration rate <0.95 (P = .005), whereas type of donor operation was not. The donors with liver restoration rate <0.95 showed lower serum albumin levels than those with liver restoration rate ≥0.95. The mean splenic enlargement rate was 1.10 ± 0.16. Right lobe donors demonstrated higher splenic enlargement rate (1.14 ± 0.18) than left lobe/lateral segment donors (1.06 ± 0.13). In the donors with splenic enlargement rate ≥1.10, platelet count was not fully restored to the preoperative level. In conclusion, older age increases the risk for incomplete postoperative liver restoration, which may be associated with a decrease in albumin more than 5 years after donation. Right lobe donation poses a risk of splenic enlargement, which is associated with incomplete restoration of platelet count.     

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.     

肝移植术后感染并发症的防治

目的　探讨肝移植术后感染并发症的防治。方法　2003年9月-2005年12月连续施行42例原位肝移植术。术后应用了一系列预防细菌、病毒、真菌感染和乙型肝炎再感染的措施。结果 42例中发生胆道感染1例，CMV感染1例，乙型肝炎复发1例。其中胆道感染及CMV感染2例分别于术后3周和6个月死亡；乙肝复发患者经治疗后HBsAg及HBV-DNA转阴。结论 合理、有效的治疗措施是预防肝移植术后感染的关键。     

儿童终末期肝病模型评分用于预测婴幼儿活体肝移植预后的作用

目的探讨儿童终末期肝病模型(PELD)评分系统用于预测婴幼儿活体肝移植预后的作用。方法回顾性分析2006年10月至2012年12月上海交通大学医学院附属仁济医院肝脏外科收治的101例小儿活体肝移植临床资料。患儿术前诊断均为胆道闭锁。术前对每例患儿进行PELD评分,根据PELD评分将患儿分为两组:低分组(PELD评分16分,62例)和高分组(PELD评分≥16分,39例)。比较两组患儿围手术期的基本情况及术后并发症发生率。结果两组患儿的手术年龄和体重差异均有统计学意义(均为P0.05),但两组性别、移植物(肝)重量/受体的体重、供肝冷缺血时间、术中失血量等差异均无统计学意义(均为P0.05)。PELD高分组患儿移植术后的肺部感染和胆道并发症发生率均明显高于低分组(均为P0.05)。结论术前PELD评分可用于预测婴幼儿肝移植的预后,为婴幼儿肝移植的围手术期的治疗、监护及护理措施的制定提供参考。对于术前PELD评分较高的患儿,应加强围手术期并发症的监护处理。     

Fatty liver caused by portal vein thrombosis after living donor liver transplantation: a case report

Portal vein thrombosis (PVT) is a rare complication that occurs after liver transplantation: however, it cannot be ignored as a cause of graft loss and death. We herein report a pediatric case of PVT that caused a fatty change in the graft after living donor liver transplantation. The portal vein was successfully reconstructed using the left great saphenous vein of the same donor. Moreover, the fatty liver recovered after the operation. Our case suggests that the finding of fatty liver is an important marker of PVT and immediate portal reconstruction is performed.