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.     

Adult Living Donor Liver Transplantation

Adult living donor liver transplantation (LDLT) begun in response to deceased donor organ shortage and waiting list mortality, grew rapidly after its first general application in the United States in 1998. There are significant risks to the living donor, including the risk of death and substantial morbidity, and two highly publicized donor deaths have led to decreased LDLT since 2001. Significant improvements in outcomes have been seen over recent years that have not been reported in single center studies; however, LDLT still comprises less than 5% of adult liver transplants, significantly less than in kidney transplantation where living donors now comprise the majority. The ethics, optimal utility and application of LDLT remain to be defined. In addition, studies to date have focused on post-transplant outcomes and not included the potential impact of LDLT on waiting time mortality. Future analyses should include appropriate control or comparison groups that capture the effect of LDLT on overall mortality from the time of listing. Further growth of LDLT will depend on defining the optimal recipient and donor characteristics for this procedure as well as broader acceptance and experience in the public and in transplant centers.     

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.     

Expanding the living liver donor pool in countries having limited deceased donor activity: Pakistani perspective

Over the last decades, liver transplantation (LT) has evolved into a life-saving procedure. Due to limited deceased donor activities in the eastern world, living donor liver transplantation (LDLT) had flourished tremendously in most Asian countries. Yet, these LDLT activities fall short of meeting the expected demands. Pakistan, a developing country, bears a major burden of liver diseases. Currently, only few centers offer LDLT services in the country. On the other hand, deceased donor liver transplantation (DDLT) activities have not started due to social, cultural, and religious beliefs. Various strategies can be adopted successfully to overcome the scarcity of live liver donors (LLDs) and to expand the donor pool, keeping in view donor safety and recipient outcome. These include consideration of LLDs with underlying clinical conditions like G6PD deficiency and Hepatitis B core positivity. Extended donor criteria can also be utilized and relaxation can be made in various donors' parameters including upper age and body mass index after approval from the multidisciplinary board. Also, left lobe grafts, grafts with various anatomical variations, and a low graft-to-recipient ratio can be considered in appropriate situations. ABO-incompatible LT and donor swapping at times may help in expanding the LLDs pool. Similarly, legislation is needed to allow live non-blood-related donors for organ donations. Finally, community education and awareness through various social media flat forms are needed to promote deceased organ donation.     

Living Donor Liver Transplantation for Patients Older Than Age 70 Years: A Single‐Center Experience

Over the past two decades, the age of liver transplantation (LT) recipients has been increasing. We reviewed our experience with LT for patients aged ≥70 years (range: 70–78 years) and investigated the feasibility of performing LT, especially living donor LT (LDLT), for older patients. We retrospectively reviewed the medical records of 25 patients (15 LDLT recipients, 10 deceased donor LT recipients) aged ≥70 years who underwent LT from January 2000 to April 2016. Their perioperative morbidity rate was 28.0%, and the in‐hospital mortality rate was 16.0%; these results were comparable to those of matched patients in their 60s (n = 73; morbidity, p = 0.726; mortality, p = 0.816). For patients in their 70s, the 1‐ and 5‐year patient survival rates were 84.0% and 69.8%, and the 1‐ and 5‐year graft survival rates were 83.5% and 75.1%, respectively. Comparisons of patient and graft survival rates between matched patients in their 60s and 70s showed no statistically significant differences (patient survival, p = 0.372; graft survival, p = 0.183). Our experience suggests that patients aged ≥70 years should not be excluded from LT, or even LDLT, based solely on age and implies that careful selection of recipients and donors as well as meticulous surgical technique are necessary for successful results.     

Living donor liver transplantation in Brazil—current state

Currently in Brazil, living donor liver transplantation (LDLT) represents 8.5% of liver transplantation (LT), being the majority pediatric one. Up to now, according to Brazilian Organ Transplantation Association (ABTO) annual report, 2,086 procedures have been done nationwide, most of them in southeast and south regions. Based on national centers reports, biliary complication is the most common recipient postoperative complication (14.5–20.6%), followed by hepatic artery thrombosis (3.1–10.7%) and portal vein thrombosis (2.3–9.1%). Patient and graft overall 5-y survival correspond to 76% and 74%, respectively. Regarding the donor, morbidity rate ranges from 12.4% to 28.3%, with a national mortality rate of 0.14%. In conclusion, Brazilian LDLT programs enhance international experience that this is a feasible and safe procedure, as well as an excellent alternative strategy to overcome organs shortage.     

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.     

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.     

Operative Risks of Domino Liver Transplantation for the Familial Amyloid Polyneuropathy Liver Donor and Recipient: A Double Analysis

Although domino liver transplantation (LT) is an established procedure, data about the operative risks are limited. This study aimed at evaluating the operative risks of domino LT. Two retrospective analyses were conducted (comparison of familial amyloid polyneuropathy [FAP] liver donors [61 patients] vs. FAP nondonors [39 patients] and FAP liver recipients [61 patients] vs. deceased donor liver recipients [61 patients]). First analysis showed a 60‐day mortality of 6.6% for FAP donors and 7.7% for FAP nondonors (p = 1.0). No patient developed primary graft nonfunction. Acute rejection was higher in FAP nondonors compared to FAP donors (38.5% vs. 13.1%). Both groups had similar vascular and biliary complication rates. ICU stay was similar, whereas total hospitalization was longer for FAP nondonors. Both groups had similar 1‐ and 5‐year patient and graft survival rates (83.4% vs. 87.2%, and 79.8% vs. 71.8%, p = 0.7) and (83.3% vs. 87.2%, and 79.1% vs.71.8%, p = 0.7). The second analysis showed a 1.6% mortality for FAP liver recipients vs. 3.2% of the control group (p = 1). Both groups had similar morbidity and technical complication rates (18.0% vs. 13.1%, p = 0.45) and (0.18 vs. 0.15, p = 0.65). The domino procedure does not add any risk to FAP donor or recipient. It increases the organ pool allowing transplantation of marginal recipients who otherwise are denied deceased donor liver transplantation.     

Liver transplantation using elderly donors: a risk factor analysis

Kim DY, Moon J, Island ER, Tekin A, Ganz S, Levi D, Selvaggi G, Nishida S, Tzakis AG. Liver transplantation using elderly donors: a risk factor analysis.
Clin Transplant 2011: 25: 270–276. © 2010 John Wiley & Sons A/S. Abstract: Survival after liver transplantation is negatively impacted by use of elderly deceased donors, but excluding them would increase waiting times and waiting list mortality. We reviewed our experience with liver transplantation (LT) utilizing livers from deceased donors 65 yr of age and older to identify those factors that impact graft survival. All adult patients (≥18 yr old) who underwent primary LT using deceased donor livers from donors aged ≥65 yr between February 1995 and November 2003 were included. With multivariate analysis we found four unfavorable characteristics significantly associated with higher post‐transplant graft failure rate. These characteristics are hepatitis C as an etiology of liver disease, Model for End‐Stage Liver Disease score >20, serum glucose level of donor >200 mg/dL at the time of liver recovery, and skin incision to aortic cross‐clamp time >40 minutes in the donor surgery. The five‐yr estimated graft survival rates having 0, 1, 2, 3, and 4 unfavorable characteristics were 100%, 82.0%, 81.7%, 39.3%, and 25.0%, respectively (p < 0.05). Our data demonstrated good graft survival can be achieved in LT using elderly donor liver allografts with appropriate patient selection, donor blood glucose management and efficient liver recovery with minimal manipulation of the liver during donor surgery.     

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.     

Expanding living donor liver transplantation: Report of first US living donor liver transplant chain

Living donor liver transplantation (LDLT) enjoys widespread use in Asia, but remains limited to a handful of centers in North America and comprises only 5% of liver transplants performed in the United States. In contrast, living donor kidney transplantation is used frequently in the United States, and has evolved to commonly include paired exchanges, particularly for ABO-incompatible pairs. Liver paired exchange (LPE) has been utilized in Asia, and was recently reported in Canada; here we report the first LPE performed in the United States, and the first LPE to be performed on consecutive days. The LPE performed at our institution was initiated by a nondirected donor who enabled the exchange for an ABO-incompatible pair, and the final recipient was selected from our deceased donor waitlist. The exchange was performed over the course of 2 consecutive days, and relied on the use and compliance of a bridge donor. Here, we show that LPE is feasible at centers with significant LDLT experience and affords an opportunity to expand LDLT in cases of ABO incompatibility or when nondirected donors arise. To our knowledge, this represents the first exchange of its kind in the United States.     

(D+10) MELD as a novel predictor of patient and graft survival after adult to adult living donor liver transplantation

We modified the previously described D‐MELD score in deceased donor liver transplant, to (D+10)MELD to account for living donors being about 10 years younger than deceased donors, and tested it on living donor liver transplantation (LDLT) recipients. Five hundred consecutive LDLT, between July 2010 and December 2012, were retrospectively analyzed to see the effect of (D+10)MELD on patient and graft survival. Donor age alone did not influence survival. Recipients were divided into six classes based on the (D+10)MELD score: Class 1 (0‐399), Class 2 (400‐799), Class 3 (800‐1199), Class 4 (1200‐1599), Class 5 (1600‐1999), and Class 6 (>2000). The 1 year patient survival (97.1, 88.8, 87.6, 76.9, and 75% across Class 1‐5, P=.03) and graft survival (97.1, 87.9, 82.3, 76.9, and 75%; P=.04) was significantly different among the classes. The study population was divided into two groups at (D+10)MELD cut off at 860. Group 1 had a significantly better 1 year patient (90.4% vs 83.4%; P=.02) and graft survival (88.6% vs 80.2%; P=.01). While donor age alone does not predict recipient outcome, (D+10)MELD score is a strong predictor of recipient and graft survival, and may help in better recipient/donor selection and matching in LDLT.     

Current role of liver transplantation for the treatment of urea cycle disorders: a review of the worldwide English literature and 13 cases at Kyoto University.

To address the current role of liver transplantation (LT) for urea cycle disorders (UCDs), we reviewed the worldwide English literature on the outcomes of LT for UCD as well as 13 of our own cases of living donor liver transplantation (LDLT) for UCD. The total number of cases was 51, including our 13 cases. The overall cumulative patient survival rate is presumed to be more than 90% at 5 years. Most of the surviving patients under consideration are currently doing well with satisfactory quality of life. One advantage of LDLT over deceased donor liver transplantation (DDLT) is the opportunity to schedule surgery, which beneficially affects neurological consequences. Auxiliary partial orthotopic liver transplantation (APOLT) is no longer considered significant for the establishment of gene therapies or hepatocyte transplantation but plays a significant role in improving living liver donor safety; this is achieved by reducing the extent of the hepatectomy, which avoids right liver donation. Employing heterozygous carriers of the UCDs as donors in LDLT was generally acceptable. However, male hemizygotes with ornithine transcarbamylase deficiency (OTCD) must be excluded from donor candidacy because of the potential risk of sudden-onset fatal hyperammonemia. Given this possibility as well as the necessity of identifying heterozygotes for other disorders, enzymatic and/or genetic assays of the liver tissues in cases of UCDs are essential to elucidate the impact of using heterozygous carrier donors on the risk or safety of LDLT donor-recipient pairs. In conclusion, LT should be considered to be the definitive treatment for UCDs at this stage, although some issues remain unresolved.     

Live Donor Liver Transplantation: A Valid Alternative for Critically Ill Patients Suffering From Acute Liver Failure

We report the outcome of live donor liver transplantation (LDLT) for patients suffering from acute liver failure (ALF). From 2006 to 2013, all patients with ALF who received a LDLT (n = 7) at our institution were compared to all ALF patients receiving a deceased donor liver transplantation (DDLT = 26). Groups were comparable regarding pretransplant ICU stay (DDLT: 1 [0–7] vs. LDLT: 1 days [0–10]; p = 0.38), mechanical ventilation support (DDLT: 69% vs. LDLT: 57%; p = 0.66), inotropic drug requirement (DDLT: 27% vs. LDLT: 43%; p = 0.64) and dialysis (DDLT: 2 vs. LDLT: 0 patients; p = 1). Median evaluation time for live donors was 24 h (18–72 h). LDLT versus DDLT had similar incidence of overall postoperative complications (31% vs. 43%; p = 0.66). No difference was detected between LDLT and DDLT patients regarding 1‐ (DDLT: 92% vs. LDLT: 86%), 3‐ (DDLT: 92% vs. LDLT: 86%), and 5‐ (DDLT: 92% vs. LDLT: 86%) year graft and patient survival (p = 0.63). No severe donor complication (Dindo–Clavien ≥3 b) occurred after live liver donation. ALF is a severe disease with high mortality on liver transplant waiting lists worldwide. Therefore, LDLT is an attractive option since live donor work‐up can be expedited and liver transplantation can be performed within 24 h with excellent short‐ and long‐term outcomes.     

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.     

Outcomes of Living Versus Deceased Donor Liver Transplantation for Acute Liver Failure in the United States

Clinical outcomes for living donor liver transplantation (LDLT) for acute liver failure (ALF) in the United States remain to be determined. To address this gap in knowledge, we examined post–liver transplantation outcomes of adults with ALF undergoing LDLT and deceased donor liver transplantation (DDLT) in the United States. We analyzed Organ and Procurement and Transplantation Network data for adults with ALF who were listed for liver transplantation as status 1 or 1A and who underwent LDLT (N = 21) or DDLT (N = 2316) between October 1987 and April 2011. We found no strong evidence that the survival probabilities for adults with ALF who underwent LDLT were inferior to those who underwent DDLT (P = .764). In adults with ALF who underwent LDLT, 1- and 5-year survival probabilities were both 71%; for DDLT these probabilities were 79% and 71%, respectively. In adults with ALF, 1- and 5-year liver graft survival probabilities, respectively, were 62% and 57% for LDLT, and 74% and 66% for DDLT. In these series of adults with ALF who were listed as status 1 or 1A, patient and graft survival rates for LDLT were similar to those for DDLT. Our findings suggest that if deceased donor livers are unavailable, LDLT is an acceptable option in experienced centers for adults with ALF.     

Adult living donor liver transplantation: body mass index and MELD score of recipients are independent risk factors for hospital mortality

Background and aims  Adult living donor liver transplantation (LDLT) has been established as elective procedure or urgent procedure to save the life of patients with terminal liver diseases. The outcome of LDLT varies between transplant centers. Here, we aim to evaluate the outcome of LDLT in our center and to identify the risk factors that are associated with hospital mortality of recipients. Patients and methods  A cohort study with 32 consecutive cases of adult living donor liver transplantation was conducted in two cooperated medical centers. Perioperative data, incidence of postoperative complications, and hospital mortality were analyzed. Results  No major surgical complications and no hospital mortality were observed in all 32 donors. All donors were discharged with normal liver function with median intensive care unit (ICU) stay of 1 day and median hospital stay of 10 days. All recipients had normal liver function in early posttransplant period. Eighty-one percent of the recipient survived with normal liver function for more than 1 year. The pretransplant ICU stay, renal failure, international normalized ratio (>1.8), and Model for End-stage Liver Disease (MELD) score (>20) were independent risk factors for hospital mortality of recipients. Conclusions  Adult living donor liver transplantation should be reserved to less “sick” patients in the era of organ allocation based on MELD score. Hans J. Schlitt and Aiman Obed shared the senior authorship of this work.     

Results of live donor liver transplantation in patients with hepatitic C virus infection: the HCV 3 trial experience

Chronic hepatitis C virus (HCV) is the most common disease indication for liver transplantation (LT). Outcomes are compromised by near universal recurrence of HCV. A prospective multi-center randomized study to evaluate immunosuppressive strategies in HCV+ transplant recipients provided the opportunity to assess impact of live donor (LD) LT. Two hundred and ninety-five patients undergoing LT for HCV (260 deceased donor [DD] recipients/35 LD recipients), randomized to three regimens, were followed for two yr for patient and graft survival and rate and severity of recurrent HCV. Biopsies were performed at baseline, 3, 12, and 24 months. One- and two-yr patient survival for LD recipients was 88.1% and 81.1% vs. 90.5% and 84.6% for DD recipients (p = 0.5665). One- and two-yr graft survival for LD recipients was 82.9% and 76.2% vs. 87.9% and 81.7% for DD recipients (p = 0.3921). Recurrent HCV did not account for more deaths or graft losses in the LD recipients. In this prospective study, controlled for immunosuppression, use of LD organs did not increase the rate or severity of HCV recurrence. The more elective nature of LDLT affords an opportunity to manipulate donor and recipient factors that can impact upon outcomes.