International Liver Transplantation Society Research Articles

Use of HBsAg-positive donors in liver transplantation: An ILTS-EASL-AASLD multisociety survey.

The gap between organ supply and demand in liver transplantation remains large in most parts of the world. One strategy to increase the donor pool is to use grafts infected with HCV, HBV, and/or HIV viruses. We aimed to explore the current use of HBsAg-positive liver grafts worldwide. A prospective cross-sectional web-based survey was designed, with a total of 28 queries, assessing national and local regulations, center experience, and center-specific experience related to the topic, and sent to all members of International Liver Transplantation Society, European Association for the Study of the Liver, and American Association for the Study of the Liver, and promoted on social media. A total of 135 liver transplant centers answered the survey: 38% from WHO European Regions, 39% from American regions, and 9.7% from South-East Asian regions. Most of the participating centers (67.3%) had been performing liver transplantation for over 15 years, with a mean of 66.5 liver transplants per year, and 54% also performed living-donor liver transplants. HBV-related disease was the indication for liver transplantation in an average of 15% of all liver transplantation cases. Regarding national and/or regional regulations, 40% of the centers reported that the use of HBsAg-positive donors was permitted, and an additional 20% could use them under special circumstances. Thirty-two centers (31%) had previously used HBsAg-positive donors. Among these centers, 62.5% conducted living-donor liver transplants and showed an increased inclination towards the use of HBsAg-positive grafts in centers with elevated waitlist mortality. HBsAg-positive donors are underutilized worldwide. The use of HBsAg-positive liver grafts could help to increase the donor pool, particularly in highly endemic areas.

An international, multicenter, survey-based analysis of practice and management of acute liver failure.

Acute liver failure (ALF) is an acute liver dysfunction with coagulopathy and hepatic encephalopathy in a patient with no known liver disease. As ALF is rare and large clinical trials are lacking, the level of evidence regarding its management is low-moderate, favoring heterogeneous clinical practice. In this international multicenter survey study, we aimed to investigate the current practice and management of patients with ALF. An online survey targeting physicians who care for patients with ALF was developed by the International Liver Transplantation Society ALF Special-Interest Group. The survey focused on management and liver transplantation (LT) practices of ALF. Survey questions were summarized overall and by geographic region. A total of 267 physicians completed the survey with a survey response rate of 21.36%. Centers from all continents were represented. More than 90% of physicians were specialized in either transplant hepatology/surgery or anesthesiology/critical care. Two hundred and fifty-two (94.4%) respondents' institutions offered LT. A total of 76.8% of respondents' centers had a dedicated liver- or transplant- intensive care unit (p<0.001). Median time to LT was within 48 hours in 12.7% of respondents' centers, 72 hours in 35.6%, one week in 37.6%, and more than one week in 9.6% (p<0.001). Deceased-donor liver graft (49.6%) was the most common type of graft offered. For consideration of LT, 84.8% of physicians used King's College Criteria and 41.6% used Clichy Criteria. Significant differences were observed between Asia, Europe, and North America for offering LT, number of LTs performed, volume of ALF patients, admission to a dedicated intensive care unit, median time to LT, type of liver graft, monitoring hepatic encephalopathy and intracranial pressure, management of coagulopathy, and utilization of different criteria for LT. In our study, we observed significant geographic differences in the practice and management of ALF. As ALF is rare multicenter studies are valuable to identify global practice.

What Is Hot and New in Basic and Translational Science in Liver Transplantation in 2023? Report of the Basic and Translational Research Committee of the International Liver Transplantation Society.

The 2023 Joint Annual Congress of the International Liver Transplantation Society, European Liver and Intestine Transplant Association, and Liver Intensive Care Group of Europe were held in Rotterdam, the Netherlands, from May 3 to 6, 2023. This year, all speakers were invited to attend the Congress in person for the first time since the COVID-19 pandemic. The congress was attended by 1159 registered delegates from 54 countries representing 5 continents, with the 10 countries comprising the bulk of the delegates. Of the 647 abstracts initially submitted, 542 were eventually presented at the meeting, coming from 38 countries (mainly North America, Europe, and Asia) and 85% of them (462 abstracts) came from only 10 countries. Fifty-three (9.8%) abstracts, originated from 17 countries, were submitted under the Basic/Translational Scientific Research category, a similar percentage as in 2022. Abstracts presented at the meeting were classified as (1) ischemia and reperfusion injury, (2) machine perfusion, (3) bioengineering and liver regeneration, (4) transplant oncology, (5) novel biomarkers in liver transplantation, (6) liver immunology (rejection and tolerance), and (7) artificial intelligence and machine learning. Finally, we evaluated the number of abstracts commented in the Basic and Translational Research Committee-International Liver Transplantation Society annual reports over the past 5 y that resulted in publications in peer-reviewed journals to measure their scientific impact in the field of liver transplantation.

Proceedings of the 28th Annual Congress of the International Liver Transplantation Society.

The 2023 Joint International Congress of the International Liver Transplantation Society (ILTS), the European Liver and Intestine Transplant Association (ELITA), and the Liver Intensive Care Group of Europe (LICAGE) held in Rotterdam, the Netherlands, marked a significant recovery milestone for the liver transplant community after COVID-19. With 1159 participants and a surge in abstract submissions, the event focused on "Liver Disorders and Transplantation: Innovations and Evolving Indications." This conference report provides a comprehensive overview of the key themes discussed during the event, encompassing Hepatology, Anesthesia and Critical Care, Acute Liver Failure, Infectious Disease, Immunosuppression, Pediatric Liver Transplantation, Living Donor Liver Transplantation, Transplant Oncology, Surgical Approaches, and Machine Perfusion. The congress provided a platform for extensive discussions on a wide range of topics, reflecting the continuous advancements and collaborative efforts within the liver transplant community.

Anesthesia and Critical Care for the Prediction and Prevention for Small-for-size Syndrome: Guidelines from the ILTS-iLDLT-LTSI Consensus Conference.

During the perioperative period of living donor liver transplantation, anesthesiologists and intensivists may encounter patients in receipt of small grafts that puts them at risk of developing small for size syndrome (SFSS). A scientific committee (106 members from 21 countries) performed an extensive literature review on aspects of SFSS with proposed recommendations. Recommendations underwent a blinded review by an independent expert panel and discussion/voting on the recommendations occurred at a consensus conference organized by the International Liver Transplantation Society, International Living Donor Liver Transplantation Group, and Liver Transplantation Society of India. It was determined that centers with experience in living donor liver transplantation should utilize potential small for size grafts. Higher risk recipients with sarcopenia, cardiopulmonary, and renal dysfunction should receive small for size grafts with caution. In the intraoperative phase, a restrictive fluid strategy should be considered along with routine use of cardiac output monitoring, as well as use of pharmacologic portal flow modulation when appropriate. Postoperatively, these patients can be considered for enhanced recovery and should receive proactive monitoring for SFSS, nutrition optimization, infection prevention, and consideration for early renal replacement therapy for avoidance of graft congestion. Our recommendations provide a framework for the optimal anesthetic and critical care management in the perioperative period for patients with grafts that put them at risk of developing SFSS. There is a significant limitation in the level of evidence for most recommendations. This statement aims to provide guidance for future research in the perioperative management of SFSS.

Preventing Small-for-size Syndrome in Living Donor Liver Transplantation: Guidelines From the ILTS-iLDLT-LTSI Consensus Conference.

Small-for-size syndrome (SFSS) is a well-recognized complication following liver transplantation (LT), with up to 20% developing this following living donor LT (LDLT). Preventing SFSS involves consideration of factors before the surgical procedure, including donor and recipient selection, and factors during the surgical procedure, including adequate outflow reconstruction, graft portal inflow modulation, and management of portosystemic shunts. International Liver Transplantation Society, International Living Donor Liver Transplantation Group, and Liver Transplant Society of India Consensus Conference was convened in January 2023 to develop recommendations for the prediction and management of SFSS in LDLT. The format of the conference was based on the Grading of Recommendations, Assessment, Development, and Evaluation system. International experts in this field were allocated to 4 working groups (diagnosis, prevention, anesthesia, and critical care considerations, and management of established SFSS). The working groups prepared evidence-based recommendations to answer-specific questions considering the currently available literature. The working group members, independent panel, and conference attendees served as jury to edit and confirm the final recommendations presented at the end of the conference by each working group separately. This report presents the final statements and evidence-based recommendations provided by working group 2 that can be implemented to prevent SFSS in LDLT patients.

Proceedings of the 27th Annual Congress of the International Liver Transplantation Society.

After a virtual congress in 2021 and a previous absence in 2020 because of the coronavirus disease 2019 pandemic, the 27th Annual Congress of the International Liver Transplantation Society was held from May 4 to 7, 2022, in a hybrid format in Istanbul, with 1123 (58% on-site) liver transplant professionals from 61 countries attending the meeting. The hybrid format successfully achieved a balance of much yearned-for "in-person interaction" and global online participation. Almost 500 scientific abstracts were presented. In this report, the Vanguard Committee aims to present a summary of key invited lectures and selected abstracts for the liver transplant community.

What Is Hot and New in Basic and Translational Science in Liver Transplantation in 2022? Report of the Basic and Translational Research Committee of the International Liver Transplantation Society.

What Is Hot and New in Basic and Translational Science in Liver Transplantation in 2022? Report of the Basic and Translational Research Committee of the International Liver Transplantation Society.

New ERAS in liver transplantation - Past, present, and next steps.

There are parallels between the history of Enhanced Recovery after Surgery (ERAS) and liver transplantation. Both have been established and advanced by innovative individuals, often going against perceived wisdom and convention. Liver transplantation has traditionally been considered too complex for ERAS pathways, despite a small number of trials showing them to be both safe and of benefit. To date, there are very few randomized controlled trials and cohort studies publishing outcomes on liver transplant patients enrolled in comprehensive ERAS pathways. To progress our field, the 2022 International Liver Transplantation Society's Consensus Conference has created expert panels to analyze the evidence in 32 domains of the liver transplantation pathway using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to generate expert recommendations. These recommendations will be voted on by the international community to gain consensus using the Danish model, and create the ERAS4OLT.org Enhanced Recovery after Liver Transplantation Pathway.

Proceedings of the 26th Annual Virtual Congress of the International Liver Transplantation Society.

After a 1-y absence due to the coronavirus disease 2019 pandemic, the 26th Annual Congress of the International Liver Transplantation Society was held from May 15 to 18, 2021, in a virtual format. Clinicians and researchers from all over the world came together to share their knowledge on all the aspects of liver transplantation (LT). Apart from a focus on LT in times of coronavirus disease 2019, featured topics of this year's conference included infectious diseases in LT, living donation, machine perfusion, oncology, predictive scoring systems and updates in anesthesia/critical care, immunology, radiology, pathology, and pediatrics. This report presents highlights from invited lectures and a review of the select abstracts. The aim of this report, generated by the Vanguard Committee of International Liver Transplantation Society, is to provide a summary of the most recent developments in clinical practice and research in LT.

Gender and Racial Disparity Among Liver Transplantation Professionals: Report of a Global Survey.

Equality, diversity, and inclusion (EDI) are fundamental principles. Little is known about the pattern of practice and perceptions of EDI among liver transplant (LT) providers. International Liver Transplant Society (ILTS) EDI Committee survey around topics related to discrimination, mentorship, and gender. Answers were collected and analyzed anonymously. Worldwide female leadership was also queried via publicly available data. The survey was e-mailed to 1312 ILTS members, 199 responses (40.7% female) were collected from 38 countries (15.2% response rate). Almost half were surgeons (45.7%), 27.6% hepatologists and 26.6% anesthetists. Among 856 LT programs worldwide, 8.2% of leadership positions were held by females, and 22% of division chiefs were female across all specialties. Sixty-eight of respondents (34.7%) reported some form of discrimination during training or at their current position, presumably related to gender/sexual orientation (20.6%), race/country of origin (25.2%) and others (7.1%). Less than half (43.7%) received mentorship when discrimination occurred. An association between female responses and discrimination, differences in compensation, and job promotion was observed. This survey reveals alarmingly high rate of experience with racial and gender disparity, lack of mentorship, and very low rates of female leadership in the LT field and calls to action to equity and inclusion.

Experience with solid organ transplantation in patients with previous immunotherapy treatment is still limited but this is changing: The survey-based view of the global transplant society

BackgroundThe use of immunotherapy for cancer is increasing and is expected to continue growing. The outcomes after solid organ transplantation(SOT) in patients who received immunotherapy before SOT remain unclear. We evaluated the global transplant surgery community's attitude towards and experience with patients who received immunotherapy for malignancy before SOT. MethodsAn online-based survey was sent to North American transplant program directors in December-2020 and members of the International Liver Transplant Society in November-2021 evaluating experiences with and attitudes towards SOT in recipients with previous immunotherapy for cancer. ResultsA total of 119 respondents completed the survey(119/175;completion rate:68%), representing centers from North America, South America, Europe, Asia, and Australia. Seventy-one(62%) respondents would consider SOT in patients with a previous history of immunotherapy for cancer, whereas thirty-nine(34%) were aware of such immunotherapy-treated recipients being transplanted, with an increasing trend over the last few years(2016[n = 1]-2020[n = 14]). Institutional clinical management policies in this setting were lacking in most centers(n = 85[75%]). ConclusionsThe international transplant community is receptive to transplanting transplant candidates previously treated with immunotherapy for cancer, although experience is still limited. In this context, more centers have started to offer SOT to patients with a history of immunotherapy for cancer in recent years. However, support from clear and robust institutional policies in this endeavor is scant. Therefore, there is a high need for consensus guidelines to inform future clinical management, especially as immunotherapy for cancer is likely to continue to increase in the coming years.

Preservation solutions for static cold storage in donation after circulatory death and donation after brain death liver transplantation in the United States.

Static cold preservation remains the cornerstone for storing donor livers following procurement; however, the choice between University of Wisconsin solution (UW) and histidine‐tryptophan‐ketoglutarate solution (HTK) remains controversial. Recent International Liver Transplantation Society (ILTS) guidelines have recommended avoiding HTK for donation after circulatory death (DCD) grafts based on older reports. We studied the latest US adult graft outcomes in three recent eras (2006–2010, 2011–2015, 2016–2020) comparing HTK and UW among 5956 DCD LTs: 3873 (65.0%) used UW and 1944 (32.7%) used HTK. In a total of 82,679 donation after brain death (DBD) liver transplantations (LTs), 63,511 (76.8%) used UW and 15,855 (19.2%) used HTK. The HTK group had higher 1‐year and 5‐year graft survival rates of 89.7% and 74.3%, respectively, compared with 85.9% and 70.8% in the UW group in the 2016–2020 era (p = 0.005). This difference remained when adjusted for important potential confounders (hazard ratio, 0.78; 95% confidence interval: 0.60, 0.99). There were no differences between groups among DCD LTs in the earlier eras or among DBD LTs in all eras (all p values > 0.05). The latest US data suggest that HTK is at least noninferior to UW for preserving DCD livers. These data support HTK use in DCD LT and contradict ILTS guidance.

The ILTS-SETH Consensus Conference on Extrahepatic Cancer and Liver Transplantation: Paving the Way.

The International Liver Transplantation Society and the Spanish Society of Liver Transplantation consensus conference on extrahepatic cancer and liver transplantation (LT) was held on January 28-30, 2021. Working groups were organized to focus on one topic and develop evidence-based recommendations specifically addressing (a) nonhepatic cancer in LT candidates, (b) de novo malignancies after LT, (c) prevention and management of donor-derived malignancies after LT, and (d) nonhepatic cancer in the pediatric population. All consensus conference attendees voted on the recommendations proposed as well as the quality of evidence according to the Grading of Recommendations, Assessment, Development and Evaluation system.

What Is Hot and New in Basic and Translational Science in Liver Transplantation in 2020-2021?-Report of the Basic and Translational Research Committee of the International Liver Transplantation Society.

What Is Hot and New in Basic and Translational Science in Liver Transplantation in 2020-2021?-Report of the Basic and Translational Research Committee of the International Liver Transplantation Society.

Comments on "Regulations and Procurement Surgery in DCD Liver Transplantation: Expert Consensus Guidance From the International Liver Transplantation Society".

To the Editor: We read with great interest the article by Hessheimer et al titled “Regulations and Procurement Surgery in DCD Liver Transplantation: Expert Consensus Guidance From the International Liver Transplantation Society.”1 The authors summarize relevant literature and provide guidelines for donation after circulatory death (DCD) liver transplant procurement on behalf of the International Liver Transplantation Society (ILTS). Our research group recently emphasized the variations in DCD organ procurement policies in the United States with a national organ procurement organization (OPO) survey.2 We discovered tremendous disparities across regions that frequently diverged from American Society for Transplant Surgeons (ASTS) recommendations for DCD procurement and the latest consensus in the literature. It is paramount to optimize graft utilization and outcomes to meet the high demand for transplantable organs and growing waitlist. We commend the authors for their important contributions. We highlight the role of asystolic wait time in DCD liver procurement that was not addressed in the work and provide observations on DCD liver transplant (LT) and machine perfusion (MP) from the United States. Our OPO survey underscored the variations in the mandatory asystolic observation period. Despite current ASTS recommendation of a 2-min waiting time, there is little standardization across institutions that vary between 2 and 5 min. Similarly, other publications have demonstrated the lack of standardization in the declaration of circulatory death.3 Additional guidance by the ILTS on these topics would optimize DCD liver procurement process to further reduce warm ischemic times and ultimately improve patient outcomes. Currently, 11 high-volume transplant centers perform nearly half (46.3%) of all DCD LT in the United States.4 However, recent changes to the allocation policies will result in wider sharing of DCD organs and increase distribution to lower volume centers. This will undoubtedly place greater emphasis on procedures to maintain outcomes, such as broader use of hypothermic machine perfusion and normothermic machine perfusion in LT. Machine perfusion with LT has shown promising results in the United States. One investigation discovered no difference in patient survival in ex vivo MP despite substantially longer CIT.5 MP has the potential to significantly improve DCD liver procurement and reduce discard rates. In 2019 alone, 1945 potential DCD livers were not transplanted including 306 grafts, which were discarded after recovery. The trend of increasing DCD LT in the United States has been accompanied with 30% discard rate compared with 7.1% for DBD LT.5 Furthermore, one center reported that only 47.9% of DCD liver offers resulted in a successful procurement, compared with 92.3% for DBD.6 Nasralla et al demonstrated 50% reduction in graft injury, discard, and postreperfusion injury rates in an normothermic machine perfusion clinical trial.7 A publication by the Groningen group on dual hypothermic oxygenated MP highlighted lower rates of nonanastomotic biliary strictures, postreperfusion syndrome, and early graft dysfunction compared with static cold storage in DCD LT.8 MP could remarkably impact the American LT waitlist by increasing potential DCD livers that are transplanted. We congratulate Hessheimer et al on their valuable contributions. We are pleased to see the growing support for procurement procedures such as withdrawal of life support treatment in the operating room and premortem heparin administration. Despite strong surgeon preference for both of these, our survey revealed that 26 OPO did not have specific regulations on the location of withdrawal of life support treatment and 3 OPO prohibited heparin use.2,3 We hope that the ILTS recommendations lead to updates in DCD procurement protocol and regulations to comply with the latest evidence in the literature. We hope to see more analyses of liver perfusion solutions and the various additives. We anticipate similar best practice guidance by the ASTS for normothermic and hypothermic regional perfusion in liver transplantation in the near future. Reduction in variable DCD liver recovery will be tremendously impactful in increasing the utilization of DCD livers and reducing graft discard rates.

Regulations and Procurement Surgery in DCD Liver Transplantation: The Custodial Role of Professional Societies in the DCD and Liver Perfusion Revolution

We thank Dr Choubey and Dr Ortiz for their interest in and insightful commentary regarding our International Liver Transplantation Society (ILTS) consensus guidelines on regulations and procurement surgery in controlled donation after circulatory death (cDCD) liver transplantation.1,2 Based on logistical and technical as well as ethical complexities associated with cDCD, we agree it is essential to have clear, consistent language describing the cDCD process and organ recovery. This is important to achieving our goals as transplant professionals of not only optimizing graft utilization rates and outcomes but also maintaining a high degree of confidence in our work among the remainder of the medical community and population at large. In their letter, Choubey and Ortiz highlight the importance of limiting donor warm ischemia in recovering organs for transplantation and achieving adequate posttransplantation outcomes. In this regard, we refer the authors to the thorough work performed by our colleagues from the ILTS Working Group on definitions and evaluation of donor warm ischemia times in cDCD.3 With respect to providing more explicit guidance on the minimum no-touch period of electrical or mechanical asystole required for declaring death, we necessarily defer to the directives of our colleagues in anesthesia and critical care. As transplant professionals, our role is to be at the ready but not to influence let alone manage decisions or care at the end of a patient’s life. Coinciding with the focus of the 2020 ILTS Consensus Conference on DCD, Liver Preservation, and Machine Perfusion, Choubey and Ortiz also describe in their letter the fact that greater use of DCD organs will be accompanied by increased use of perfusion technologies. These include not only ex situ modalities hypothermic and normothermic machine perfusion but also in situ normothermic regional perfusion (NRP). While at present, ex situ machine perfusion treats a single organ after a variable length of cold ischemia, NRP restores oxygenated blood flow to the kidneys, liver, and pancreas (abdominal NRP) or all aforementioned organs plus the heart and lungs (thoracoabdominal NRP) immediately following donor cardiac arrest and declaration of death. As such, it effectively converts the period of donor hypoperfusion and arrests into one of ischemic preconditioning, restoring energy substrates, removing metabolic waste products, and increasing levels of endogenous antioxidants before cold preservation and recovery. For the liver, these benefits have translated into the successful transplantation of cDCD livers from older donors or with prolonged donor warm ischemia times, with graft and patient survival rates comparable with those seen with donation after brain death livers and minimal to no ischemic biliary injury observed in published multicenter experiences.4,5 Given current trends, clinical application of cDCD liver transplantation will continue to expand in the coming years. We, as professionals and societies, have an important role as custodians in this process, and we must continue to provide experience-, evidence-, and value-based directives to help guide the DCD and liver perfusion revolution.

Hemodynamic Instability During Liver Transplantation in Patients With End-stage Liver Disease: A Consensus Document from ILTS, LICAGE, and SATA.

Hemodynamic instability (HDI) during liver transplantation (LT) can be difficult to manage and increases postoperative morbidity and mortality. In addition to surgical causes of HDI, patient- and graft-related factors are also important. Nitric oxide-mediated vasodilatation is a common denominator associated with end-stage liver disease related to HDI. Despite intense investigation, optimal management strategies remain elusive. In this consensus article, experts from the International Liver Transplantation Society, the Liver Intensive Care Group of Europe, and the Society for the Advancement of Transplant Anesthesia performed a rigorous review of the most current literature regarding the epidemiology, causes, and management of HDI during LT. Special attention has been paid to unique LT-associated conditions including the causes and management of vasoplegic syndrome, cardiomyopathies, LT-related arrhythmias, right and left ventricular dysfunction, and the specifics of medical and fluid management in end-stage liver disease as well as problems specifically related to portal circulation. When possible, management recommendations are made.

Is There a Place for Induction Therapy With Polyclonal Antibodies to Improve Renal Function After Liver Transplantation?

Is There a Place for Induction Therapy With Polyclonal Antibodies to Improve Renal Function After Liver Transplantation?

Early Allograft Dysfunction and Complications in DCD Liver Transplantation: Expert Consensus Statements From the International Liver Transplantation Society.

Livers for transplantation from donation after circulatory death donors are relatively more prone to early and ongoing alterations in graft function that might ultimately lead to graft loss and even patient death. In consideration of this fact, this working group of the International Liver Transplantation Society has performed a critical evaluation of the medical literature to create a set of statements regarding the assessment of early allograft function/dysfunction and complications arising in the setting of donation after circulatory death liver transplantation.