Small-for-size syndrome in adult-to-adult living-related liver transplantation

Small-for-size syndrome (SFSS) in adult-to-adult living-related donor liver transplantation (LRLT) remains the greatest limiting factor for the expansion of segmental liver transplantation from either cadaveric or living donors. Portal hyperperfusion, venous pathology, and the arterial buffer response signif icantly contribute to clinical and histopathological manifestations of SFSS. Here, we review the technical aspects of surgical and radiological procedures developed to treat SFSS in LRLT, along with the pathophysiology of this condition.

Clinical study on safety of adult-to-adult living donor liver transplantation in both donors and recipients

AIM: To investigate the safety of adult-to-adult living donor liver transplantation (A-A LDLT) in both donors and recipients. METHODS: From January 2002 to July 2006, 50 cases of A-A LDLT were performed at West China Hospital, Sichuan University, consisting of 47 cases using right lobe graft without middle hepatic vein (MHV), and 3 cases using dual grafts (one case using two left lobe, 2 using one right lobe and one left lobe). The most common diagnoses were hepatitis B liver cirrosis, 30 (60%) cases; and hepatocellular carcinoma, 15 (30%) cases in adult recipients. Among them, 10 cases had the model of end-stage liver disease (MELD) with a score of more than 25. Donor screening consisted of reconstruction of the hepatic blood vessels and biliary system with 3-dimension computed tomography and volumetry of whole liver and right liver volume. Various improved surgical techniques were adopted in the procedures for both donors and recipients . RESULTS: Forty-nine right lobes and 3 left lobes (2 left lobe grafts for 1 recipient, 1 left lobe graft for 1 recipient who had received right lobe graft donated by relative living donor) were obtained from 52 living donors. The 49 right lobe grafts, without MHV, weighed 400 g-850 g (media 550 g), and the ratio of graft volume to recipient standard liver volume (GV/SLV) ranged from 31.74% to 71.68% (mean 45.35%). All donors' remnant liver volume was over 35% of the whole liver volume. There was no donor mortality. With a follow-up of 2-52 mo (media 9 mo), among 50 adult recipients, complications occurred in 13 (26%) cases and 4 (8%) died postoperatively within 3 mo. Their 1-year actualsurvival rate was 92%. CONCLUSION: When preoperative CT volumetry shows volume of remnant liver is more than 35%, the ratio of right lobe graft to recipients standard liver volume exceeding 40%, A-A LDLT using right lobe graft without MHV should be a very safe procedure for both donors and recipients, otherwise dual grafts liver transplantation should be considered.

Feasibility of ABO-incompatible adult living donor liver transplantation for acute-on-chronic liver failure

To the Editor:In Korea,the annual number of deceased donors for or gan transplantation per million people is still less than10.Thus,approximately 40%of patients with acute liver failure or acute-on-chronic liver failure undergo living donor liver transplantation（LDLT）.;Although the use of ABO-incompatible（ABOi）living donors is an attrac tive option,ABOi LDLT has very restricted applications

Some aspects of adult living donor liver transplantation:small-for-size graft and ABO mismatch

Living donor liver transplantation (LDLT) was first performed for pediatric patients, for whom the gap between demand and supply of

Adult-to-adult living donor liver transplantation for acute liver failure in China

AIM:To investigate the long-term outcome of recipients and donors of adult-to-adult living-donor liver transplantation(AALDLT) for acute liver failure(ALF).METHODS:Between January 2005 and March 2010,170 living donor liver transplantations were performed at West China Hospital of Sichuan University.All living liver donor was voluntary and provided informed consent.Twenty ALF patients underwent AALDLT for rapid deterioration of liver function.ALF was defined based on the criteria of the American Association for the Study of Liver Diseases,including evidence of coagulation abnormality [international normalized ratio(INR) ≥ 1.5] and degree of mental alteration without pre-ex-isting cirrhosis and with an illness of < 26 wk duration.We reviewed the clinical indications,operative procedure and prognosis of AALDTL performed on patients with ALF and corresponding living donors.The potential factors of recipient with ALF and corresponding donor outcome were respectively investigated using multivariate analysis.Survival rates after operation were analyzed using the Kaplan-Meier method.Receiver operator characteristic(ROC) curve analysis was undertaken to identify the threshold of potential risk factors.RESULTS:The causes of ALF were hepatitis B(n = 18),drug-induced(n = 1) and indeterminate(n = 1).The score of the model for end-stage liver disease was 37.1 ± 8.6,and the waiting duration of recipients was 5 ± 4 d.The graft types included right lobe(n = 17) and dual graft(n = 3).The mean graft weight was 623.3 ± 111.3 g,which corresponded to graft-torecipient weight ratio of 0.95% ± 0.14%.The segment Ⅴor Ⅷ hepatic vein was reconstructed in 11 right-lobe grafts.The 1-year and 3-year recipient's survival and graft survival rates were 65%(13 of 20).Postoperative results of total bilirubin,INR and creatinine showed obvious improvements in the survived patients.However,the creatinine level of the deaths was increased postoperatively and became more aggravated compared with the level of the survived recipients.Multivariate analysis showed that waiting duration was independently correlated with increased mortality(P = 0.014).Furthermore,ROC curve revealed the cut-off value of waiting time was 5 d(P = 0.011,area under the curve = 0.791) for determining the mortality.The short-term creatinine level with different recipient's waiting duration was described.The recipients with waiting duration ≥ 5 d showed the worse renal function and higher mortality than those with waiting duration < 5 d(66.7% vs 9.1%,P = 0.017).In addition,all donors had no residual morbidity.Furthermore,univariate analysis did not show that short assessment time induced the high morbidity(P = 0.573).CONCLUSION:Timely AALDLT for patients with ALF greatly improves the recipient survival.However,further systemic review is needed to investigate the optimal treatment strategy for ALF.

Split liver transplantation in adults

Split liver transplantation(SLT),while widely accepted in pediatrics,remains underutilized in adults. Advancements in surgical techniques and donor-recipient matching,however,have allowed expansion of SLT from utilization of the right trisegment graft to now include use of the hemiliver graft as well. Despite less favorable outcomes in the early experience,better outcomes have been reported by experienced centers and have further validated the feasibility of SLT. Importantly,more than two decades of experience have identified key requirements for successful SLT in adults. When these requirements are met,SLT can achieve outcomes equivalent to those achieved with other types of liver transplantation for adults. However,substantial challenges,such as surgical techniques,logistics,and ethics,persist as ongoing barriers to further expansion of this highly complex procedure. This review outlines the current state of SLT in adults,focusing on donor and recipient selection based on physiology,surgical techniques,surgical outcomes,and ethical issues.

Modified techniques for adult-to-adult living donor liver transplantation

BACKGROUND: Because of critical organ shortage, transplant professionals have utilized living donor liver transplantation (LDLT) in recent years. We summarized our experience in adult-to-adult LDLT with grafts of right liver lobe by a modified technique. METHODS: From January 2002 to August 2005, 24 adult patients underwent living donor liver transplantation with grafts of the right liver lobe at West China Hospital, Sichuan University, China. Twenty-two patients underwent modi-Bed procedures designed to improve the reconstruction of the right hepatic vein and the tributaries of the middle hepatic vein by interposing a great saphenous vein ( GSV) graft and the anastomosis of the hepatic arteries and bile ducts. RESULTS: No severe complications and death occurred in all donors. In the first 2 patients, (patients 1 and 2), operative procedure was not modified. One patient suffered from 'small-for-size syndrome' and the other died of sepsis with progressive deterioration of graft function. In the rest 22 patients (patients 3 to 24), however, the procedure of venous reconstruction was modified, and better results were obtained. Complications occurred in 7 recipients including acute rejection (2 patients), hepatic artery thrombosis (1), bile leakage (1), intestinal bleeding (1), left sub-phrenic abscess (1), and pulmonary infection (1). One patient with pulmonary infection died of multiple organ failure (MOF). The 22 patients underwent direct anastomosis of the right hepatic vein to the inferior vena cava (IVC), 9 direct anastomosis plus the reconstruction of the right inferior hepatic vein, and 10 direct anastomosis plus the reconstruction of the tributaries of the middle hepatic vein by in-terpos-ing a GSV graft to provide sufficient venous outflow. Trifurcation of the portal vein was met in 3 patients. Venoplasty or separate anastomosis was performed. The ratio of graft to recipient body weight ranged from 0.72% to 1.17%. Among these patients, 19 had the ratio <1.0% and 4 <0.8%, and the ratio of graft weight to recipient standard liver volume was between 31.86% and 62.48%. Among these patients, 10 had the ratio <50% and 2 <40%. No 'small-for-size syndrome' occurred in the 22 recipients who were subjected to modified procedures. CONCLUSIONS: With the modified surgical techniques for the reconstruction of the hepatic vein to obtain an adequate outflow and provide a sufficient functioning liver mass, living donor liver graft in adults using the right lobe can be safe to prevent the 'small-for-size syndrome'.

Reconstruction of the middle hepatic vein tributary in adult right lobe living donor liver transplantation

BACKGROUND: In adult-to-adult living donor liver transplantation (LDLT), the use of a right lobe graft without the middle hepatic vein (MHV) can cause hepatic congestion and disturbance of venous drainage. To solve this problem, we successfully used cadaveric venous allografts preserved in 4 ℃ University of Wisconsin (UW) solution within 10 days as interposition veins for drainage of the paramedian portion of the right lobe in adult LDLT. METHODS: From June 2007 to January 2008, 11 adult LDLT patients received modified right liver grafts. The major MHV tributaries (greater than 5 mm in diameter) of 9 cases were preserved and reconstructed using cadaveric interposition vein allografts that had been stored for 1 to 10 days in 4 ℃ UW solution. The regeneration of the paramedian sector of the grafts and the patency of the interposition vein allografts were examined by Doppler ultrasonography after the operation. RESULTS: MHV tributaries were reconstructed in 9 recipients. Only 1 recipient died of renal failure and severe pulmonary infection on day 9 after transplantation without any hemiliver venous outflow obstruction. The other 8 recipients achieved long-term survival with a median follow-up of 30 months. The cumulative patency rates of the 8 recipients were 63.63% (7/11), 45.45% (5/11), 45.45% (5/11) and 36.36% (4/11) at 3, 6, 12 and 24 months, respectively. Regeneration of the paramedian sectors was equivalent.CONCLUSION: The cadaveric venous allograft preserved in 4 ℃ UW solution within 10 days serves as a useful alternative for interposition veins in facilitating implantation of a right lobe graft and guarantees outflow of the MHV.

Liver transplantation for a giant mesenchymal hamartoma of the liver in an adult: Case report and review of the literature

Mesenchymal hamartomas of the liver(MHLs) in adults are rare and potentially premalignant lesions, which present as solid/cystic neoplasms. We report a rare case of orthotopic liver transplantation in a patient with a giant MHL. In 2013, a 34-year-old female sought medical advice after a 2-year history of progressive abdominal distention and respiratory distress. Physical examination revealed an extensive mass in the abdomen. Computed tomography(CT) of her abdomen revealed multiple liver cysts, with the diameter of largest cyst being 16 cm × 14 cm. The liver hilar structures were not clearly displayed. The adjacent organs were compressed and displaced. Initial laboratory tests, including biochemical investigations and coagulation profile, were unremarkable. Tumor markers, including levels of AFP, CEA and CA19-9, were within the normal ranges. The patient underwent orthotopic liver transplantation in November 2013, the liver being procured from a 40-year-old man after cardiac death following traumatic brain injury. Warm ischemic time was 7.5 min and cold ischemic time was 3 h. The recipient underwent classical orthotopic liver transplantation. The recipient operative procedure took 8.5 h, the anhepatic phase lasting for 1 h without the use of venovenous bypass. The immunosuppressive regimen includedintraoperative induction with basiliximab and high-dose methylprednisolone, and postoperative maintenance with tacrolimus, mycophenolate mofetil, and prednisone. The recipient's diseased liver weighed 21 kg(dry weight) and measured 41 cm × 32 cm × 31 cm. Histopathological examination confirmed the diagnosis of an MHL. The patient did not experience any acute rejection episode or other complication. All the laboratory tests returned to normal within one month after surgery. Three months after transplantation, the immunosuppressive therapy was reduced to tacrolimus monotherapy, and the T-tube was removed after cholangiography showed no abnormalities. Twelve months after transplantation, the patient remains well and is fulfilling all normal activities. Adult giant MHL is extremely rare. Symptoms, physical signs, laboratory results, and radiographic imaging are nonspecific and inconclusive. Surgical excision of the lesion is imperative to make a definite diagnosis and as a cure. Liver transplantation should be considered as an option in the treatment of a non-resectable MHL.

Developing a donation after cardiac death risk index for adult and pediatric liver transplantation

AIM To identify objective predictive factors for donor after cardiac death(DCD) graft loss and using those factors, develop a donor recipient stratification risk predictive model that could be used to calculate a DCD risk index(DCD-RI) to help in prospective decision making on organ use.METHODS The model included objective data from a single institute DCD database(2005-2013, n = 261). Univariate survival analysis was followed by adjusted Cox-regressional hazard model. Covariates selected via univariate regression were added to the model via forward selection, significance level P = 0.3. The warm ischemic threshold was clinically set at 30 min. Points were given to each predictor in proportion to their hazard ratio. Using this model, the DCD-RI was calculated. The cohort was stratified to predict graft loss risk and respective graft survival calculated.RESULTS DCD graft survival predictors were primary indication for transplant(P = 0.066), retransplantation(P = 0.176), MELD > 25(P = 0.05), cold ischemia > 10 h(P = 0.292) and donor hepatectomy time > 60 min(P = 0.028).According to the calculated DCD-RI score three risk classes could be defined of low(DCD-RI < 1), standard(DCD-RI 2-4) and high risk(DCD-RI > 5) with a 5 years graft survival of 86%, 78% and 34%, respectively.CONCLUSION The DCD-RI score independently predicted graft loss(P < 0.001) and the DCD-RI class predicted graft survival(P < 0.001).

Adult to adult living related liver transplantation: Where do we currently stand?

Adult to adult living donor liver transplantation (AALDLT) was first preformed in the United States in 1997. The procedure was rapidly integrated into clinical practice, but in 2002, possibly due to the first widely publicized donor death, the number of living liver donors plummeted. The number of donors has since reached a steady plateau far below its initial peak. In this review we evaluate the current climate of AALDLT. Specifically, we focus on several issues key to the success of AALDLT: determining the optimal indications for AALDLT, balancing graft size and donor safety, assuring adequate outflow, minimizing biliary complications, and maintaining ethical practices. We conclude by offering suggestions for the future of AALDLT in United States transplantation centers.

De novo malignancies after liver transplantation: The effect of immunosuppression-personal data and review of literature

BACKGROUND Immunosuppression has undoubtedly raised the overall positive outcomes in the post-operative management of solid organ transplantation. However, long-term exposure to immunosuppression is associated with critical systemic morbidities. De novo malignancies following orthotopic liver transplants (OLTs) are a serious threat in pediatric and adult transplant individuals. Data from different experiences were reported and compared to assess the connection between immunosuppression and de novo malignancies in liver transplant patients. AIM To study the role of immunosuppression on the incidence of de novo malignancies in liver transplant recipients. METHODS A systematic literature examination about de novo malignancies and immunosuppression weaning in adult and pediatric OLT recipients was described in the present review. Worldwide data were collected from highly qualified institutions performing OLTs. Patient follow-up, immunosuppression discontinuation and incidence of de novo malignancies were reported. Likewise, the review assesses the differences in adult and pediatric recipients by describing the adopted immunosuppression regimens and the different type of diagnosed solid and blood malignancy.RESULTS Emerging evidence suggests that the liver is an immunologically privileged organ able to support immunosuppression discontinuation in carefully selected recipients. Malignancies are often detected in liver transplant patients undergoing daily immunosuppression regimens. Post-transplant lymphoproliferative diseases and skin tumors are the most detected de novo malignancies in the pediatric and adult OLT population, respectively. To date, immunosuppression withdrawal has been achieved in up to 40% and 60% of well-selected adult and pediatric recipients, respectively. In both populations, a clear benefit of immunosuppression weaning protocols on de novo malignancies is difficult to ascertain because data have not been specified in most of the clinical experiences. CONCLUSION The selected populations of tolerant pediatric and adult liver transplant recipients greatly benefit from immunosuppression weaning. There is still no strong clinical evidence on the usefulness of immunosuppression withdrawal in OLT recipients on malignancies. An interesting focus is represented by the complete reconstitution of the immunological pathways that could help in decreasing the incidence of de novo malignancies and may also help in treating liver transplant patients suffering from cancer.

Liver transplantation and artificial liver support in fulminant hepatic failure

INTRODUCTIONFulminant hepatic failure(FHF)is a severe disease with devastating consequences;the incidence is high in China.Before the availability of liver transplantation,the mortality rate was more than 80%[1,2].The advent of liver transplantation revolutionized the outcome of FHF[3,4].However,many patients were unwilling to accept liver transplantation until very late,hence most of them died because of donor shortage and urgency of the disease[5-7],To overcome he problems,we performed orthotopic liver transplantation(OLT)in combination with artificial liver support(ALS) in the treatment of FHF in the past 2 years with satisfactory results.Our experience was reported below.

Initial steroid-free immunosuppression after liver transplantation in recipients with hepatitis c virus related cirrhosis

AIM: Steroids can increase hepatitis C virus (HCV) replication. After liver transplantation (LTx), steroids are commonly used for immunosuppression and acute rejection is usually treated by high steroid dosages. Steroids can worsen the outcome of recurrent HCV infection. Therefore,we evaluated the outcome of HCV infected liver recipients receiving initial steroid-free immunosuppression.METHODS: Thirty patients undergoing LTx received initial steroid-free immunosuppression. Indication for LTx included 7 patients with HCV related drrhosis. Initial immunosuppression consisted of tacrolimus 2x0.05 mg/kg.d po and mycophenolate mofetil (MMF) 2x15 mg/kg.d po. The tacrolimus dosage wasa djusted to trough levels in the target range of 10-15 μg/Ldudng the first 3 mo and 5-10 μg/L thereafter. Manifestations of acute rejection were verified histologically.RESULTS: Patient and graft survival of 30 patients receiving initial steroid-free immunosuppression was 86% and 83% at 1 and 2 years. Acute rejection occurred in 8/30 patients,including 1 HCV infected recipient. All HCV-infected patients had HCV genotype II (lb). HCV seropositivity occurred within the first 4 mo after LTx. The virus load was not remarkably increased during the first year after LTx. Histologically, grafts had no severe recurrent hepatitis.CONCLUSION: From our experience, initial steroid-free immunosuppression does not increase the risk of acute rejection in HCV infected liver recipients. Furthermore, none of the HCV infected patients developed serious chronic liver diseases. It suggests that it may be beneficial to avoid steroids in this particular group of patients after LTx.

成人肝移植术后营养状况及影响因素的研究进展

对国内外成人肝移植受者术后营养状况的发生现状、发生机制、评估指标和方法及其相关影响因素进行综述并提出展望,以期为临床护理实践和研究提供参考和借鉴。

成人肝移植术后疼痛变化轨迹及影响因素分析

目的分析成人肝移植术后疼痛变化轨迹及影响因素,为制订针对性的护理措施缓解成人肝移植术后疼痛提供参考。方法采用目的抽样法选择在某三甲医院麻醉科行肝移植的138例成人患者,采用疼痛数字评定量表(NRS)于患者手术当天、术后第1天上午、术后第1天下午、术后第2天上午、术后第2天下午、术后第3天上午、术后第3天下午进行调查,评估患者的疼痛程度。采用潜分类增长模型(LCGM)识别疼痛变化轨迹的潜在类别;运用时间不变协变量的潜增长曲线模型(LGCM)分析其影响因素;纳入协变量运用混合回归模型(MRM)分析各潜在类别的影响因素。结果疼痛变化轨迹可分为疼痛低组(64.5%)、疼痛快速上升组(22.5%)、疼痛缓慢上升组(13.0%)。纳入协变量的分析结果显示,年龄、诊断、术中低体温是影响术后疼痛的轨迹类别(均P<0.05或0.001)。结论成人肝移植患者术后疼痛分为3种不同的变化轨迹,其术后疼痛存在群体异质性,应基于患者术后疼痛变化轨迹的同质群体,有针对性地进行评估和干预。

他克莫司缓释胶囊在远期成人肝移植受者中的临床诊治体会

目的探讨他克莫司缓释胶囊在肝功能稳定的远期成人肝移植受者中的临床应用价值。方法回顾2018年1月至2023年1月北京清华长庚医院随访的远期肝移植受者转换为他克莫司缓释胶囊的临床资料,分析应用他克莫司缓释胶囊前、后不同时间点肝功能、肾功能、他克莫司药物浓度、CD4^(+)T细胞数量变化趋势。结果肝移植术后应用他克莫司缓释胶囊患者共21例,男性女性比为13∶8。平均年龄为(60.07±8.24)岁。转换时间(距肝移植手术)为(28.85±49.47)个月。他克莫司普通剂型与缓释剂型剂量比为1∶1.03。与转换前相比,换药后2、4、12周丙氨酸转氨酶(alanine aminotransferase,ALT)、天冬氨酸转氨酶(aspartate aminotransferase,AST)、γ-谷氨酰转移酶(γ-glutamyl transpeptadase,GGT)、碱性磷酸酶(alkaline phosphatase,ALP)、肌酐(creatinine,Cre)、尿素氮(bloodureanitrogen,BUN)、CD4+T细胞数量及他克莫司浓度相比无统计学意义。3例患者出现肝功能轻微波动,增加他克莫司缓释胶囊剂量后肝功能恢复正常。结论肝功能稳定的远期成人肝移植患者由他克莫司普通剂型等比例转换为他克莫司缓释剂型后,肝功能稳定,排斥反应发生率低,肾功能改善不明显。

Outcomes of adult-to-adult living donor liver transplantation： a single center experience

Background Since January 2002, adult-to-adult living donor liver transplantation （AALDLT） has gained increasing popularity in China in response to the shortage of cadaveric donor livers. This study presents a detailed analysis of the outcomes of AALDLT in a single center. Methods A total of 70 patients underwent AALDLT at our center between January 2002 and January 2007. Among these, 67 patients received a right lobe graft without the middle hepatic vein and 3 patients received dual grafts. Three-dimensional volumetric computed tomography, magnetic resonance imaging with angiography and cholangiography were performed preoperatively. Recipient operation time, intraoperative transfusion requirement, length of intensive care unit stay, length of hospital stay, liver function tests, coagulation tests and surgical outcomes were routinely investigated throughout this study. Results All donors survived the procedure with an overall complication rate of 15.3%. Overall recipient 1-year survival and complication rates were 87.1% and 34.2%, respectively. Among the 70 cases, average graft recipient weight ratio was 0.94% （0.72%-1.43%） and average graft volume/standard liver volume ratio was 46.42% （31.74%-71.68%）. All residual liver volumes exceeded 35%. Liver function and coagulation recovered rapidly within the first 7 days after transplantation. Conclusions AALDLT is a safe procedure for the donors and an effective therapy for patients with end-stage liver disease. Patient selection and timely decision-making for transplantation are essential in achieving good outcomes. With accumulation of experience in surgery and clinical management, timely feedback and proper modification, we foresee better outcomes in the future.

美国肝病学会和美国移植学会2012年实践指南:成人肝移植成功后的长期管理

1序言 本实践指南经由美国肝病学会和美国移植学会联合批准通过。本指南为已经成功接受了成人肝移植的受体提供了一个基于数据支持的术后长期管理策略。本指南的撰写基于以下几个方面：（1）正式的已经发表的来自世界各国的回顾和分析性文献（通过Medline题目检索获得）;（2）美国医师协会卫生实践评估手册;（3）实践指南,包括美国肝病学会关于发展 和应用的政策性实践指南，以及美国胃肠病学会对实践指南的政策说明；（4）指南作者在专业领域的实践经验。

美国肝病学会和美国移植学会2013实践指南:成人肝移植评估(推荐意见)

本指南由美国肝病学会（AASLD）和美国移植学会（AST）联合发布。评估肝移植的指南是由AASLD2005年发表的。迄今慢性肝病的治疗已经取得了重大进展，特别是慢性病毒性肝炎的抗病毒治疗。非酒精性脂肪肝作为导致肝硬化和肝细胞癌而需要肝移植的病因，越来越引起关注。此外，肝移植的个别疾病的适应证如肝癌已经被规范，慢性病毒性肝炎也有专门的指南。评估肝移植这个有各种中年期特有合并症的复杂群体需要多学科方法，指南反映了这一需求，推荐建议已发展到协助他们心脏病的管理。随着肝移植长期存活者越来越多，他们的生活质量以及影响寿命的共存因素更受到关注。该指南目的是为潜在的肝移植候选成人患者的移植评估提供循证医学证据。