Current status of organ transplantation in Japan and worldwide

Recent advances in immunosuppressant therapy have dramatically reduced the frequency of acute rejection of organ transplants. Subsequently, the short-term graft survival rate has been improved, and ABO blood type-incompatible and existing anti-HLA antibody-positive kidney transplantation has been enabled, which has increased the availability of living kidney donors. Japan has a unique history and strategies of liver transplantation (LT) for various liver diseases. The outcomes of living donor liver transplantation (LDLT) in Japan is comparable to that of deceased donor liver transplantation (DDLT) in Western countries despite the relatively short history of LT. The main disadvantage of LT in Japan is donor shortage mainly due to the small number of available deceased donors. There are some disadvantages with LDLT in autoimmune liver diseases because of the dependence on blood relative donors. The first brain-dead pancreas transplantation (PTx) was performed in 2000. Since that time, 42 brain-dead PTx, 2 non-heart beating PTx, and 14 living donor PTx had been performed by the end of 2007. One of the 44 recipients of deceased donor PTx died of unknown causes 11 months after transplantation. Although most of the deceased donors in Japan were marginal and their condition was not favorable, the results of these cases were comparable to those of Western countries. Fourteen intestinal transplantations (ITx) had been performed by the end of 2007 in four transplant centers. There were 3 deceased donor and 11 live donor transplants. The original diseases included short bowel syndrome (n = 6), intestinal function disorder (n = 6), and retransplantation (n = 2). The graft and patient survival rate are 60% and 69%, respectively. Eight recipients survived and stopped parenteral nutrition with full-functioning grafts. Amendment of the Japanese law for the utilization of deceased donors should increase the number available donors in the future.     

Living donor liver transplantation in Egypt

In Egypt there is no doubt that chronic liver diseases are a major health concern. Hepatitis C virus (HCV) prevalence among the 15−59 years age group is estimated to be 14.7%. The high prevalence of chronic liver diseases has led to increasing numbers of Egyptian patients suffering from end stage liver disease (ESLD), necessitating liver transplantation (LT). We reviewed the evolution of LT in Egypt and the current status. A single center was chosen as an example to review the survival and mortality rates. To date, deceased donor liver transplantation (DDLT) has not been implemented in any program though Egyptian Parliament approved the law in 2010. Living donor liver transplantation (LDLT) seemed to be the only logical choice to save many patients who are in desperate need for LT. By that time, there was increase in number of centers doing LDLT (13 centers) and increase in number of LDLT cases [2,400] with improvement of the results. Donor mortality rate is 1.66 per 1,000 donors; this comprised four donors in the Egyptian series. The exact recipient survival is not accurately known however, and the one-year, three-year and five-year survival were 73.17%, 70.83% and 64.16% respectively in the International Medical Center (IMC) in a series of 145 adult to adult living donor liver transplantation (AALDLT) cases. There was no donor mortality in this series. LDLT are now routinely and successfully performed in Egypt with reasonable donor and recipient outcomes. Organ shortage remains the biggest hurdle facing the increasing need for LT. Although LDLT had reasonable outcomes, it carries considerable risks to healthy donors. For example, it lacks cadaveric back up, and is not feasible for all patients. The initial success in LDLT should drive efforts to increase the people awareness about deceased organ donation in Egypt.     

Live donor liver transplantation for acute liver failure

BACKGROUND: Acute liver failure (ALF) carries a high mortality unless urgent orthotopic liver transplantation (OLT) is performed on time. Live donors are utilized to treat this irreversible condition first in pediatric cases and then in adults. Herein, we aimed to report our experience with live donors for ALF in a country of a deceased donor organ donation rate is only 1.5 per million people. METHODS: Among the 245 live donor liver transplantations (LDLT) performed from June 1999 to December 2005, 14 of them (6%) were performed for ALF in 8 pediatric and 6 adult cases. Right lobes were harvested for the adult cases whereas left lateral segments were harvested for pediatric cases, except one child transplanted with a right lobe graft. The etiology of the disease was; acute hepatitis B in four cases, hepatitis A in three cases, Wilson disease two cases, autoimmune hepatitis in two cases, and was unknown in three cases. RESULTS: Three-year graft and patient survival is 79% for these series. Five of the six adult patients and six of the eight pediatric cases survived after transplantation. There was not any donor mortality or major morbidity. CONCLUSIONS: LDLT offers a safe and effective modality of treatment for ALF for both pediatric and adult patients to overcome the problem of organ shortage especially in countries where the chance of receiving an organ from a deceased donor is low.     

Review of anesthesia in liver transplantation

Liver transplantation (LT) is a well-accepted treatment modality of many end-stage liver diseases. The main issue in LT is the shortage of deceased donors to accommodate the needs of patients waiting for such transplants. Live donors have tremendously increased the pool of available liver grafts, especially in countries where deceased donors are not common. The main ethical concern of this procedure is the safety of healthy donors, who undergo a major abdominal surgery not for their own health, but to help cure others. The first part of the review concentrates on live donor selection, preanesthetic evaluation, and intraoperative anesthetic care for living liver donors. The second part reviews patient evaluation, intraoperative anesthesia monitoring, and fluid management of the recipient. This review provides up-to-date information to help improve the quality of anesthesia, and contribute to the success of LT and increase the long-term survival of the recipients.     

Hepatitis C recurrence and fibrosis progression are not increased after living donor liver transplantation: a single-center study of 289 patients.

Today, hepatitis C virus (HCV) is the leading cause for liver transplantation (LT) and viral recurrence is almost universal. It has been suggested that viral replication within the transplanted tissue might be increased in organs of reduced size such as LD grafts. In the current literature the data is controversial, with many studies lacking routine liver biopsies. We performed a retrospective analysis of 289 HCV-LT (20 LD splits) patients receiving transplants between 1997 and 2005. Patient and organ survival, intensity of HCV recurrence, and fibrosis progression were analyzed with respect to deceased donor (DD) LT (DDLT) or living donor (LD) LT (LDLT). Organ and patient survival was significantly better for full-size recipients than for split-liver patients, with P = 0.037 for organ survival and P = 0.037 for patient survival; yet there were no significant differences when split-liver patients with large hepatocellular carcinoma (HCC) beyond the Milan criteria (n = 3) were excluded from the analysis (P > 0.05). First year fibrosis progression was 1.29 in full-size grafts and 1.07 in split-livers (P = not significant). In conclusion, in our patient sample, intensity of HCV recurrence was not increased in LD graft recipients compared to full-size recipients. Patient and organ survival were similar when patients with large HCC and early tumor recurrence were excluded from analysis. LDLT can therefore be advocated for HCV patients.     

Liver transplantation for HBsAg‐positive recipients using grafts from HBsAg‐positive deceased donors

This study reports our experience using deceased donor liver grafts from HBsAg‐positive donors. We performed eight cases of liver transplantation (LT) using grafts from deceased HBsAg‐positive donors between November 2005 and October 2010. The median age of donors was 48 years (range: 26–64). HBV DNA in the serum of donors ranged from 44 to 395 IU/ml, but HBeAg in all donors was negative. Preoperative laboratory and liver biopsy samples revealed the absence of definitive cirrhotic features and hepatitis. All recipients showed HBsAg positive preoperatively except one patient with HBsAg(?) status post previous LT for HBV related liver cirrhosis. The median age was 60 years (range: 46–76) at LT. Post‐LT antiviral management consisted of hepatitis B immunoglobulin and antiviral nucleos(t)ide analogues. The median follow‐up period was 25.5 months (range: 14–82). Of eight recipients, two recipients experienced serum HBsAg and HBV DNA disappearance postoperatively. Three recipients died of HBV‐unrelated causes. The remaining five recipients were stable with normal liver function and no marked pathologic changes on follow‐up biopsies. This experience shows that LT using grafts from deceased HBsAg‐positive donors is feasible, and may represent a valuable expansion of the pool of organ donors with appropriate antiviral management and monitoring.     

Living donor liver transplantation for hepatitis C

Liver cirrhosis and hepatocellular carcinoma related to chronic hepatitis C virus (HCV) infection are currently the most common indications for liver transplantation. The number of living donor liver transplantation (LDLT) procedures has increased given the shortage of donor organs from deceased donors. However, recurrence of HCV infection is universal and affects graft survival. This mini-review compared the outcomes for HCV-positive recipients after LDLT with those after deceased donor liver transplantation.     

成人间双供体活体肝脏移植成功2例报告

目的供肝短缺是影响肝脏移植发展的主要因素之一，活体供肝是解决这一矛盾的重要措施，供者提供足够的肝脏是影响活体肝脏移植的重要因素。方法施行成人间双供体活体肝移植2例，1例由受者的两位姐姐分别提供左半肝作为供肝，另1例由受者母亲提供右半肝，由无心跳供者提供左半肝(采用劈裂方式，其另一部分肝脏同时为另一成人受者实施肝脏移植)作为供肝。结果术后供、受者肝功能均恢复良好。结论成人问双供肝活体肝脏移植可以为受者提供更大重量的肝脏，又可减少供者提供较多肝脏所带来的风险；双供肝一受者肝脏移植手术操作复杂。     

Live donor liver transplantation.

With ever-increasing demand for liver replacement, supply of organs is the limiting factor and a significant number of patients die while waiting. Live donor liver transplantation has emerged as an important option for many patients, particularly small pediatric patients and those adults that are disadvantaged by the current deceased donor allocation system. Ideally there would be no need to subject perfectly healthy people in the prime of their lives to a potentially life-threatening operation to procure transplantable organs. Donor safety is imperative and cannot be compromised regardless of the implication for the intended recipient. The evolution of split liver transplantation is the basis upon which live donor transplantation has become possible. The live donor procedures are considerably more complex than whole organ decreased donor transplantation and there are unique considerations involved in the assessment of any specific recipient and donor. Donor selection and evaluation have become highly specialized. The critical issue of size matching is determined by both the actual size of the donor graft and the recipient as well as the degree of recipient portal hypertension. The outcomes after live donor liver transplantation have been at least comparable to those of deceased donor transplantation. Nevertheless, all efforts should be made to improve deceased donor donation so as to minimize the need for live donors. Transplant physicians, particularly surgeons, must take responsibility for regulating and overseeing these procedures.     

Ten years survival with excellent outcome after living donor liver transplantation from 70 years old donor for primary hepatic neuroendocrine carcinoma: Case report

BACKGROUNDPrimary hepatic carcinoid tumors (PHCT) are rare entities; they are even rarer than extrahepatic neuroendocrine gastrointestinal tumors with only about 95 cases reported in the literature. An extrahepatic primary tumor must be excluded to confirm the diagnosis of PHCT.CASE PRESENTATIONWe report a case of a 42-year-old male patient with a primary hepatic neuroendocrine carcinoma, who successfully underwent living donor liver transplantation from his 70 years old mother with 10 years follow-up. Both donor and recipient are still alive and in the good health.CONCLUSIONLiving liver donation from elderly donors for the patients with irresectable neuroendocrine liver malignancies can be as safe as deceased donation or liver donation from young donors (age < 50). Living donation from elderly donors might significantly expand the donor pool for patients with liver neuroendocrine tumors (NET) and potentially reduce waiting list mortality. Especially young patients with irresectable NET can benefit from this option. However, case–control studies are needed to verify the advantage of living liver transplantation (LDLT) for the patients with irresectable liver NET and to define selection criteria for these patients.     

Safety of donor in adult-to-adult living donor liver transplantation using right lobe graft

BACKGROUND: The growing gap between the number of patients awaiting liver transplantation and available organs has continued to be the primary issue facing the transplant community. To overcome the waiting list mortality, living donor liver transplantation has become an option, in which the greatest concern is the safety of the donor, especially in adult-to-adult living donor liver transplantation (A-A LDLT) using a right lobe liver graft. OBJECTIVE: We evaluated the safety of donors after right lobe liver donation for A-A LDLT performed in our center. METHODS: From January 2002 to March 2006, 26 patients underwent A-A LDLT using right lobe liver grafts in our center. Seven donors were men and 19 were women (range, 19-65 years; median age, 38 years). The right lobe liver grafts were obtained by transecting the liver on the right side of the middle hepatic vein without interrupting the vascular blood flow. The mean follow-up time for these donors was 9 months. RESULTS: These donor residual liver volumes ranged from 30.5% to 60.3%. We did not experience any donor mortality. Two cases (7.69%) experienced major complications: intra-abdominal bleeding and portal vein thrombosis in one each and three (11.54%), minor ones: wound steatosis in two, and transient chyle leak in one. All donors were fully recovered and returned to their previous occupations. CONCLUSIONS: A-A LDLT using a right lobe liver graft has become a standard option. The donation of right lobe liver for A-A LDLT was a relatively safe procedure in our center.     

Donor outcomes in right lobe adult living donor liver transplantation: single-center experience in Egypt

INTRODUCTION AND OBJECTIVES: Living donor liver transplantation (LDLT) is an alternative source of organs for patients with end-stage liver disease (ESLD) in absence of deceased donor LT. In LDLT the greatest concern is donor safety. Our objective was to evaluate the outcome of donors after right lobe liver donation in a single LT center in Egypt. PATIENTS AND METHODS: Fifty LDL resections were performed from 2001 to 2004. The mean donor age was 29.2 +/- 6.4 years. Residual liver volume was 41.1 +/- 4.5%. Mean operative time was 560 +/- 62.2 minutes; mean ICU stay, less than 24 hours; mean hospital stay, 15.4 +/- 7.7 days; and mean follow-up period, 6 months. RESULTS: There was no mortality. The overall complication rate was 68% (34 donors). Major complications included intraoperative bleeding in one, biliary leak in two, and pneumonia in three donors. Minor complications included mild pleural effusion in 13 donors, transient ascites in 10, mild depression in 7, intra-abdominal collections in 3, and wound infections in 1 donor. Residual liver volume did not affect the complication rate. None required reoperation. Return to predonation activity occurred within 6 to 8 weeks. No liver impairment occurred during follow-up. CONCLUSION: Right lobe adult LDLT is a safe procedure with regard to donor outcome. Major complications occurred in only 10% of our series.     

Selection of liver-transplant candidates for adult-to-adult living donor liver transplantation as the only surgical option for end-stage liver disease.

The selection of living donor liver transplantation (LDLT) recipients in regions where deceased donor liver transplantation (DDLT) is rarely performed might be different from that in other centers at which LDLT is an alternative option to DDLT. Records of adult (age > or = 18 yr) patients referred to our center were reviewed to analyze the selection process of LDLT candidates. Among the 533 LDLT candidates, 165 (31%) were rejected due to recipient issues. Advanced hepatocellular carcinoma (HCC) was the most common reason for rejection (n = 55). Among the remaining recipients, 120 patients (22%) were rejected due to donor issues. LDLT was eventually performed in 249 (47%) of the evaluated recipients. There are few options for candidates who are unable to find live donors in regions where DDLT is unrealistic. A more effective and precise approach to recipient and donor evaluation should be pursued.     

Progress in living donor liver transplantation for biliary atresia and challenges faced: A thirty-year single institutional experience

BackgroundBiliary atresia (BA) is the most common indication for liver transplantation in the pediatric population, and living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) have been established as a radical treatment for BA .The aim of this study was to clarify the long term outcomes and risk factors affecting the LDLT outcomes, as well as the challenges faced.MethodsBetween 1990 and 2019, 666 BA patients underwent LDLT in our institution and were enrolled in this study. Data regarding the recipient's age, anatomic findings of the biliary tree at Kasai's portoenterostomy, basic characteristics at transplantation, transplant profiles, donor characteristics, and outcomes of LDLT were analyzed.ResultsThe 1-, 5-, 10-, 15-, 20-, and 25-year graft survival rates of BA patients who underwent LDLT were 88.1%, 85.4%, 81.5%, 78.9%, 76.6%, and 75.5%, respectively. The transplant era, age at transplantation, ABO incompatible transplant, and presence of pulmonary vascular complications were identified as significant risk factors for overall graft survival. When the study period was divided into the first (1990–1999) and second (2000–2019) phases and re analyzed, the outcomes of ABO-incompatible transplants and LDLT for adult BA patients remained inferior to others in the second phase. The 20-year graft survival rate in patients who underwent re transplantation in the second phase was 54.2%.ConclusionsThe outcomes of LDLT in children are generally good, but the immunosuppression procedures need to be further improved for ABO-incompatible cases in the future. Further improvements in LDLT results for adult patients and re transplantation remain challenges to be addressed in this field, and future attempts, including revision to the organ allocation system of deceased donors, are necessary.Level of evidenceLevel III (case control study).     

Live donor liver transplantation in adults

Live donor liver transplantation (LDLT) was initiated in 1988 for children recipients. Its application to adult recipients was limited by graft size until the first right liver LDLT was performed in Hong Kong in 1996. Since then, right liver graft has become the major graft type. Despite rapid adoption of LDLT by many centers, many controversies on donor selection, indications, techniques, and ethics exist. With the recent known 11 donor deaths around the world, transplant surgeons are even more cautious than the past in the evaluation and selection of donors. The need for routine liver biopsy in donor evaluation is arguable but more and more centers opt for a policy of liberal liver biopsy. Donation of the middle hepatic vein (MHV) in the right liver graft was considered unsafe but now data indicate that the outcome of donors with or without MHV donation is about equal. Right liver LDLT has been shown to improve the overall survival rate of patients with chronic liver disease, acute or acute-on-chronic liver failure and hepatocellular carcinoma waiting for liver transplantation. The outcome of LDLT is equivalent to deceased donor liver transplantation despite a smaller graft size and higher technical complexity.     

The challenge of finding donors for living donor liver transplantation in Saudi Arabia

INTRODUCTION: Organ shortage remains the main limiting factor for expanding liver transplantation (LT) in Saudi Arabia. Therefore, living donor liver transplantation (LDLT) was recently undertaken by our team at King Faisal Specialist Hospital and Research Center (KFSH&RC), in an effort to meet the increasing demand for LT in Saudi Arabia. OBJECTIVE: Analysis of donors assessed for LDLT at KFSH&RC. METHODS: Between September 2002 and May 2003, 39 potential donors were assessed for LDLT. First- or second-degree relationship to the recipient was an essential precondition. Assessment included biochemical testing, radiological studies (computed tomography: magnetic resonance angiography, magnetic resonance cholangiography), and thorough psychosocial analysis. Liver biopsy and hepatic angiogram was performed in some but not all donors. RESULTS: Male:female ratio was 28:11. Median age was 27 (18 to 34). Of 39 potential donors, only three underwent LDLT. The remaining 36 were rejected for different reasons including: psychosocial in 8 (20.5%), fatty liver in 7 (17.9%), recipient issues in 6 (15.4%), refusal after initial approval in 3 (7.7%), unfavorable anatomy in 2 (5.1%), inadequate liver volume in 2 (5.1%), abnormal liver functions in 2 (5.1%), hepatitis C virus in 2 (5.1%), liver pathology in 1 (2.6%), and other medical concerns in remaining 3 donors (7.7%). CONCLUSION: In Saudi Arabia, donor availability as well as recipient characteristics may limit the value of LDLT in overcoming organ shortage. Therefore, efforts should be directed to improve the number and quality of available cadaveric organs. Until then, LDLT may be the only way forward to save patients from dying on the waiting list.     

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.     

Right lobe living-donor hepatectomy—the Toronto approach,tips and tricks

Living-donor liver transplantation (LDLT) is a well-established treatment for end-stage liver disease. Nevertheless, it has not been extensively accepted in North America or Europe as it has been in Asia. At the University of Toronto we initiated our LDLT program in 2000 and since then our program has grown each year, representing today the largest LDLT program in North America. Our right-lobe LDLT experience from 2000−2014 includes 474 right lobes. Only 30% of our grafts have included the middle hepatic vein. We present excellent outcomes in terms of graft and patient survival which is not different to that achieved with deceased donor liver transplantation. In the present study we will discuss the evolution, challenges and current practices of our LDLT program. We will discuss what is and has been the program philosophy. We will also discuss how we evaluate our donors and the extensive workup we do before a donor is accepted for live donation. Furthermore we will discuss some tips and tricks of how we perform the right hepatectomy for live donation.