In the United States, living donor liver transplant (LDLT), from both directed and nondirected living donors, has expanded over the past several years. LDLT is viewed as an important opportunity to expand the overall donor pool for liver transplantation (LT), shorten waiting times for a life-prolonging LT surgery, and reduce LT waitlist mortality. The LT community's focus on LDLT expansion in the United States is fostering discussions around future opportunities, which include the safe expansion of donor and recipient candidate eligibility criteria, broadening indications for LDLT including applications in transplant oncology, developing national initiatives around liver paired exchange, and maintaining vigilance to living donor and recipient candidate risk/benefit equipoise. Potential opportunities for expanding living liver donor and recipient candidate criteria include using donors with more than minimal hepatic steatosis, evaluating older donors, performing LDLT in older recipients to facilitate timely transplantation, and providing candidates who would benefit from an LT, but may otherwise have limited access (ie, lower MELD scores), an avenue to receive a life-prolonging organ. Expansion opportunities for LDLT are particularly robust in the transplant oncology realm, including leveraging LDLT for patients with advanced HCC beyond Milan, intrahepatic cholangiocarcinoma, and nonresectable colorectal cancer liver metastases. With ongoing investment in the deliberate growth of LDLT surgical expertise, experience, and technical advances in the United States, the LT community's future vision to increase transplant access to more patients with end-stage liver disease and selected oncology patients may be successfully realized.

Biliary atresia is a progressive cholangiopathy in neonates, which often results in liver failure. In high-income countries, initial treatment requires prompt diagnosis followed by Kasai portoenterostomy. For those with a late diagnosis, or those in whom Kasai portoenterostomy fails, liver transplantation is the only lifesaving treatment. Unfortunately, in low- and middle-income countries, timely diagnosis is a challenge and liver transplantation is rarely accessible. Here, we discuss the ethical dilemmas surrounding treatment of babies with biliary atresia in Uganda. Issues that require careful consideration include: risk of catastrophic health expenditure to families, ethical dilemmas of transplant tourism, medical risks of maintaining the transplant in a low-resourced health system, and difficult decisions encountered by the surgeon caring for these patients. Four distinct models of the patient-physician relationship are applied to biliary atresia in Uganda. These models describe differences in patient and physician roles, and patient values and autonomy. Solid organ transplantation is a rapidly evolving segment of healthcare in Uganda and ongoing policy advancements may shift ethical considerations in the future.

Living donor liver transplantation (LDLT) was first performed in the US in 1989, primarily benefiting pediatric patients. Its adoption for adults faced setbacks after a donor death in 2001, causing widespread risk aversion. Despite ethical justification and demonstrated safety, LDLT remains underutilized, with fewer than 10% of liver transplants being LDLT. Recent trends indicate improved access to deceased donor liver transplantation (DDLT) due to increased organ donation and technological advances like Normothermic Regional Perfusion (NRP). However, LDLT remains critical, especially for pediatric patients and specific adult populations who benefit significantly from it. Barriers to LDLT include public and clinician apprehensions about donor risks, despite studies showing low-complication rates. Non-directed donations and broader social media engagement have increased donor pools, though the volume of LDLT in the US remains lower than in Asia due to limited training and experience. The A2ALL consortium has been pivotal in studying LDLT safety and outcomes. Currently, around 40 US centers perform LDLT, with high-volume centers leading by example. Training paradigms for LDLT are evolving, with initiatives like the ASTS LDLT master class aiming to enhance surgical expertise. While LDLT is embedded in US liver-transplant practices, its expansion is hampered by risk aversion and the availability of DDLT. Nonetheless, LDLT is essential for addressing the supply-demand mismatch in liver transplantation.

Recent modifications in organ allocation policies and increases in chronic liver diseases may have resulted in important changes in living donor liver transplantation (LDLT) in the United States. We examined the trends, outcomes, and factors associated with outcomes in adult LDLT. United Network for Organ Sharing data on 2566 adult LDLT recipients who received transplants from January 1, 2010, through December 31, 2019, were analyzed. LDLT graft and patient survival rates were compared with propensity score-matched deceased donor liver transplantation recipients by the Kaplan-Meier curve estimator. The association between preceding LDLT frequency and subsequent outcomes were assessed by Cox proportional hazards mixed effects modeling. After a stable annual frequency of LDLTs from 2010 to 2014 (~200 per year), the number of LDLTs doubled to 440 in 2019. The 1-year and 5-year graft survival rates for LDLT recipients were 88.4% and 78.1%, respectively, compared with 92.5% and 80.7% in the propensity score-matched donation after brain death recipients (P = 0.005), respectively. Older donor age and recipient diabetes mellitus and life support requirement were significantly associated with graft failure among LDLT recipients (P values <0.05). Average preceding LDLT frequencies of <3 per year, 3 to 20 per year, and >20 per year resulted in 1-year graft survival rates of 82%, 88% to 89%, and 93%, respectively (P values <0.05). There were 3 living donor deaths (0.12%). The frequency of LDLTs has doubled during the past decade, with good outcomes and acceptable donor safety profiles. However, there appear to be varying threshold transplant frequencies (volume/unit time) associated with acceptable (88%-89%) and aspirational (93%) 1-year graft survival rates. These data should be reassuring and encourage LDLT practice as efforts continue to expand the donor pool.

Paired organ exchange can be used to circumvent living donor-recipient ABO incompatibilities. Herein, we present the first case of successful liver paired exchange in North America. This 2-way swap required 4 simultaneous operations: 2 living donor hepatectomies and 2 living donor liver transplants. A nondirected anonymous living donor gift initiated this domino exchange, alleviating an ABO incompatibility in the other donor-recipient pair. With careful attention to ethical and logistical issues, paired liver exchange is a feasible option to expand the donor pool for incompatible living liver donor-recipient pairs.

Rereading Renée C. Fox's "A Sociological Perspective on Organ Transplantation and Hemodialysis," published in 1970, one is likely to be struck more by continuity than by change. The most pressing of the social, policy, and ethical concerns that Fox raised remain problematic fifty years later. We still struggle with scientific and clinical uncertainty, with the boundary between experimentation and therapy, and with the cost of organ replacement therapies and disparities in how they are allocated. We still have an imperfect understanding of transplant immune responses. We still debate when a potential donor "actually" dies, and we still seem to think better empirical criteria could harmonize the diverse religious, cultural, and socioeconomic values of patients, providers, third-party payers, and policy-makers. Organ transplantation was for Fox both a particular case unfolding in time and an entryway for discussing the difficult moral questions presented by many new medical technologies in a context of high demand and limited resources.

Whether living liver donors have a higher risk of biliary tract disease compared with non-donors remains unknown.

Data were collected from the Taiwan Longitudinal Health Insurance Database for the 2003-2011 period. The study cohort comprised 1,446 patients aged ≥ 18 years who had served as living liver donors. The primary outcome was the incidence of biliary tract disease. Cox proportional hazards modeling was used to determine the hazard ratios.

The incidence density rate of biliary tract disease was 13.9-fold higher in the liver donor (LD) cohort than in the non-LD cohort (10.2 vs. 0.71 per 1,000 person-years), with an adjusted hazard ratio (HR) of 14.2 (95% confidence interval [CI] = 7.73-26.1). Stratified by comorbidity, the relative risk of biliary tract disease was higher in the LD cohort than in the non-LD cohort for both patients with or without comorbidity. The incidence density rate of biliary tract disease was significantly higher in the first 3 years (13.5 per 1,000 person-years in the LD cohort). The highest adjusted HR of biliary tract disease for LD patients compared with the non-LD cohort was 22.4 (95% CI = 10.8-46.1) in the follow-up ≤ 3 years.

Living liver donors had a higher risk of biliary tract disease compared with non-donors.

Living donation has become a medically and ethically accepted practice in solid organ transplantation. Published proceedings from the international kidney transplant community and from the Ethics Committee of The Transplantation Society articulated the general principles and specific recommendations for living donation, which remain the backbone of Centers for Medicare and Medicaid Services and Organ Procurement and Transplantation Network requirements and policies. Meanwhile, there have been major advancements in another revolutionary field of transplant medicine: vascularized composite allotransplantation. Recent interventions have demonstrated potential for superior functional and aesthetic outcomes in a single operation when compared to staged conventional reconstructions. In view of these successes, the indications for vascularized composite allotransplantation are expected to broaden to include less extensive types of transplants, which would introduce the possibility of using living vascularized composite allotransplantation donors. In this article, the authors discuss the feasibility and ethics associated with living donation of vascularized composite allografts. The authors explore the current guidelines and policies set by the Organ Procurement and Transplantation Network regarding living organ donation. In addition, the authors provide several clinical scenarios in which living donation of vascularized composite allotransplantation could be used to augment the reconstructive ladder currently used by reconstructive surgeons to guide their reconstructive strategies.

Kidney paired exchange (KPE) constitutes 12% of all living donor kidney transplantations (LDKTs) in the United States. The success of KPE programs has prompted many in the liver transplant community to consider the possibility of liver paired exchange (LPE). Though the idea seems promising, the application has been limited to a handful of centers in Asia. In this article, we consider the indications, logistical issues, and ethics for establishing a LPE program in the United States with reference to the principles and advances developed from experience with KPE. Liver Transplantation 24 677-686 2018 AASLD.

Living donation provides important access to organ transplantation, which is the optimal therapy for patients with end-stage liver or kidney failure. Paired exchanges have facilitated thousands of kidney transplants and enable transplantation when the donor and recipient are incompatible. However, frequently willing and otherwise healthy donors have contraindications to the donation of the organ that their recipient needs. Trans-organ paired exchanges would enable a donor associated with a kidney recipient to donate a lobe of liver and a donor associated with a liver recipient to donate a kidney. This article explores some of the ethical concerns that trans-organ exchange might encounter including unbalanced donor risks, the validity of informed consent, and effects on deceased organ donation.

Living donor liver transplantation (LDLT) is a technically demanding endeavor, requiring command of the complex anatomy of partial liver grafts. We examined the influence of anatomic variation and reconstruction techniques on surgical outcomes and graft survival in the 9-center Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). Data from 272 adult LDLT recipients (2011-2015) included details on anatomic characteristics and types of intraoperative biliary reconstruction. Associations were tested between reconstruction technique and complications, which included first biliary complication (BC; leak, stricture, or biloma) and first vascular complication (VC; hepatic artery thrombosis [HAT] or portal vein thrombosis [PVT]). Time to patient death, graft failure, and complications were estimated using Kaplan-Meier curves and tested with log-rank tests. Median posttransplant follow-up was 1.2 years. Associations were found between the type of biliary reconstruction and the incidence of VC (P = 0.03) and BC (P = 0.05). Recipients with Roux-en-Y hepaticojejunostomy had the highest probability of VC. Recipients with biliary reconstruction involving the use of high biliary radicals on the recipient duct had the highest likelihood of developing BC (56% by 1 year) compared with duct-to-duct (42% by 1 year). In conclusion, the varied surgical approaches in the A2ALL centers offer a novel opportunity to compare disparate LDLT approaches. The choice to use higher biliary radicals on the recipient duct for reconstruction was associated with more BC, possibly secondary to devascularization and ischemia. The use of Roux-en-Y biliary reconstruction was associated with VCs (HAT and PVT). These results can be used to guide biliary reconstruction decisions in the setting of anatomic variants and inform further improvements in LDLT reconstructions. Ultimately, this information may contribute to a lower incidence of technical complications after LDLT. Liver Transplantation 23 1519-1530 2017 AASLD.

This review presents the author's personal perspective and contributions to the first steps, the development, the current status, and the remaining issues of pediatric liver transplantation (LT). Innumerable children around the world who have undergone LT have reached adulthood. The techniques have reached maturity. As shown by my own group's experience, grafts donated by living donors might provide the best short-term and longterm results. Debate persists about the optimal immunosuppression (IS), although the place of tacrolimus remains unchallenged. Tolerance induction protocols aiming to induce microchimerism have been tried in clinical transplantation without convincing results. Withdrawal of maintenance IS is possible in some children who underwent liver transplantation who have excellent clinical status and normal liver function tests but is not without risk of rejection and subsequent worsening of histology. The current trend favored by the Brussels' group is to minimize IS as soon after transplant as possible, aiming to obtain a state of "prope" or "almost" tolerance. Liver grafts are threatened in the long term by increasing hepatitis-related fibrosis, resulting most likely from immunological assault. Nowadays, the focus is on the longterm survival, quality of life (growth, academic performance, employment, self-fulfillment, fertility, raising a family, etc.), induction of tolerance, prevention of risks bound to decades of IS (nephrotoxicity and neurotoxicity, cardiovascular risk, de novo malignancies, etc.), and prevention of graft fibrosis. All these issues are fertile fields for younger scientists. Liver Transplantation 22 1284-1294 2016 AASLD.

Innovation is responsible for most advances in the field of surgery. Innovative approaches to solving clinical problems have significantly decreased morbidity and mortality for many surgical procedures, and have led to improved patient outcomes. While innovation is motivated by the surgeon's expectation that the new approach will be beneficial to patients, not all innovations are successful or result in improved patient care. The ethical dilemma of surgical innovation lies in the uncertainty of whether a particular innovation will prove to be a "good thing." This uncertainty creates challenges for surgeons, patients, and the healthcare system. By its very nature, innovation introduces a potential risk to patient safety, a risk that may not be fully known, and it simultaneously fosters an optimism bias. These factors increase the complexity of informed consent and shared decision making for the surgeon and the patient. Innovative procedures and their associated technology raise issues of cost and resource distribution in the contemporary, financially conscious, healthcare environment. Surgeons and institutions must identify and address conflicts of interest created by the development and application of an innovation, always preserving the best interest of the patient above the academic or financial rewards of success. Potential strategies to address the challenges inherent in surgical innovation include collecting and reporting objective outcomes data, enhancing the informed consent process, and adhering to the principles of disclosure and professionalism. As surgeons, we must encourage creativity and innovation while maintaining our ethical awareness and responsibility to patients.

Pediatric liver transplantation (LTx) has revolutionized life chances and perspectives of children with liver disease. Following rapid establishment of the therapeutic concept in the early years of pediatric transplant medicine, more aspects beyond plain survival become increasingly important. In addition to improving the short to medium-term survival rates, researchers are focusing on themes such as rehabilitation, adherence and quality of life, long-term graft fibrosis and dysfunction, as well as the consequences of long-term immunosuppression. Also, more protocol biopsy data are available to evaluate increasing graft fibrosis. To manage their conditions, patients will need access to highly experienced pediatric liver transplant centers where clinical research will examine modulators of renal disease, endocrine and cardiovascular comorbidity and the development of graft fibrosis and malignancies. Assessment and evaluation of health-related quality of life and factors which influence clinical tolerance, adherence and transition from child to adult care will also be investigated. The analysis of multi-national registry data and more than 40years of experience with large patient cohorts will provide important clues to treatment and will thus get increasing attention. In the future, longitudinal assessment of the outcome for pediatric LTx patients should include more functional aspects than plain survival rates or laboratory parameters.

Radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) are treatment methods for patients with early-stage hepatocellular carcinoma (HCC) who are not suitable for surgery. Although some reports indicate that RFA is better than PEI, results from previous reviews and analyses are inconsistent. Therefore, this meta-analysis was performed to more thoroughly evaluate the effects of these treatments in patients with HCC.

A literature search was conducted using the Excerpta Medica dataBASE, PubMed, the Cochrane Library, the American Society of Clinical Oncology database, the China National Knowledge Infrastructure database, the Wanfang database, the Chinese Biomedical Literature Database, and the Chongqing VIP database without language limitations. The primary outcome evaluated was overall survival, and secondary outcomes included complete response and local recurrence. Comparisons were made between Asian and European studies.

Total pooled and subgroup analyses of Asian studies that included selection biases revealed that RFA is superior to PEI with respect to overall survival (hazard ratio (HR), 0.54; 95% confidence interval (CI), 0.37 to 0.80; P < 0.01) and complete response (relative risk (RR), 1.10; 95% CI 1.03 to 1.18; P < 0.01). However, no significant difference was observed between RFA and PEI in the European studies. In Asian studies, RFA was associated with a lower local recurrence rate than PEI at 1 year (RR, 0.44; 95% CI 0.20 to 0.95; P < 0.05) and 3 years (RR, 0.35; 95% CI 0.22 to 0.55; P < 0.01). However, local recurrence was significantly lower after only 3 years in European studies (RR, 0.50; 95% CI 0.32 to 0.78; P < 0.05).

RFA was only superior to PEI in Asian studies that included selection bias. Thus, there is insufficient evidence to support the idea that RFA is superior to PEI for patients with cirrhotic HCC. Additional large-scale, multicenter, randomized controlled trials that control for selection bias are needed to fully elucidate the optimal treatment method for HCC.

The ethics of the clinical practice of transplanting human organs for end-stage organ disease is a fascinating topic. Who is the "owner" of the transplantable organs of a deceased, brain-dead patient? Who should have a right to receive these organs? Who set the boundaries between a living donor's autonomy and a "paternalistic" doctor? What constitutes a proper consent? These questions are only some of the ethical issues that have been discussed in the last 60 years. All of these ethical issues are intensified by the fact that supply of human organs does not match demand, and that, as a consequence, living-donor organ transplantation is widely utilized. The aim of this article is not to be exhaustive but to present the general ethical principles of beneficence, nonmaleficence, and justice as applied to organ transplantation. Moreover, the topic of reimbursement for organ donation is also discussed.

Due to the limited number of cadaver donors, adult living liver donor transplantation became an alternative for liver transplantation. During living liver donor transplantation, the safety and uncomplicated recovery of the donor are as important as the appropriate volume and weight of the donated graft. The middle hepatic vein causes a significant dilemma, due to the special anatomical position. The reconstruction of the middle hepatic vein branches supplying S5, S8 is suggested when the anatomically right liver lobe is transplanted.

The aim of the present study was to investigate the requirements of the reconstruction of middle hepatic vein and to give an accurate description about the discrepancy between the portal vein in- and outflow.

The authors analyzed the liver anatomic characteristics of 130 donors undergoing living liver donor transplantation with the use of MeVis software. The so-called porto-hepatic disparity index (shift) was introduced.

The right hepatic vein was dominant in 64.6% of all cases, while the left hepatic vein was never observed to be dominant. The territories of V5 and V8 were responsible for the 33.2±8.9% of the right hepatic lobe area. The correlation between portal venous territory and vein dominancy were as follows: R2 = 0.7811 in the left liver lobe; R² = 0.5463 in the area of middle hepatic vein and R² = 0.5843 in the case of the right hepatic vein. The average value of the shift was 28.2%.

The differences among the pattern of portal in- and hepatic outflow is an important issue that should be taken into consideration when deciding the necessity for reconstruction of the middle hepatic vein.

Uterus transplantation (UTx) is an alternative to gestational surrogacy and adoption for patients with absolute uterine infertility. Studies have been conducted in animals, and UTx is now within the reach of clinical application in humans. Procedures in humans have been published, but many medical, ethical, and social problems and risks of UTx require discussion prior to widespread clinical application, from the perspectives of donors, recipients, families, and newborns. In this article, we summarize the burdens and risks of UTx, with a focus on donors who provide the uterus.

Radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) have been used for patients with hepatocellular carcinomas (HCCs) < 3 cm, but there is controversy which of the two methods is superior. Therefore, we aimed to conduct a systematic review to assess survival, complete tumor necrosis, recurrence and metastasis, major complications, costs, hospital stays, and posttreatment survival quality of RFA versus PEI for treating small HCCs < 3 cm.

We conducted a search for published articles in PubMed, Embase, and the Cochrane Library until March 2012. Only randomized controlled trials (RCTs) and quasi-randomized clinical trials were included.

Four RCTs with 766 patients were included in this review. We found that RFA is significantly better than PEI with respect to a 3-year overall survival for small HCCs (RFA vs PEI, hazard ratios [HR] = 0.66, 95% confidence interval [CI]: 0.48-0.90, P = 0.009), especially for HCCs > 2 cm (HR = 0.56, 95% CI: 0.31-0.99, P = 0.045). RFA had a lower risk of local recurrence (HR = 0.38, 95% CI: 0.15-0.96, P = 0.040), but no difference is seen for distant intrahepatic recurrence. RFA had higher rates of complete tumor necrosis, but RFA also caused more major complications and was more costly than PEI. Begg's and Egger's tests detected no significant publication bias among the four RCTs.

RFA appears superior to PEI with respect to local tumor control and 3-year survival for small HCCs < 3 cm. RFA was more feasible in patients with HCCs > 2 cm or Child-Pugh A liver function.

Deceased donor liver transplantation has been an established surgical procedure since the 1960s. More recently, the technique of living donor liver transplantation (LDLT) was introduced, and it is being performed with increasing frequency. However, there is a paucity of information on the clinical outcomes of donor patients. In this study, which was conducted at a single university hospital, the relationship between potentially relevant factors (eg, patient characteristics, preoperative status, and operation characteristics) and postoperative developments in donor patients was examined. We used electronic critical pathways, which are charts of medical process that include favorable states (defined as outcomes) to be achieved during the hospital stay of a patient; predefined outcomes that are not achieved are recorded as variances. With the electronic critical pathway system, objective data about the conditions of patients and relevant clinical processes could be collected readily. Using data from the electronic critical pathways for LDLT donor patients and applying multiple logistic regression analysis, we examined factors that were related to the variance of each outcome measure for postoperative developments. Among the various donor characteristics, the duration of the operation was related to variance in 5 types of health outcomes, age and blood loss volume were related to variance in 2 types of health outcomes, and other characteristics (ie, sex, body surface area, operation urgency, and volume ratio of the remnant liver) were related to variance in 1 type of health outcome. In conclusion, the findings in this study may facilitate improvements in the postoperative status of LDLT donor patients. Further studies that incorporate analogous data from other medical facilities are necessary to verify these findings.