Donor Pool Research Articles

The First ABO Incompatible Kidney Transplantation from Living Donor in Slovakia – A Challenge How to Expand the Kidney Donor Pool

Abstract Kidney transplantation is the most effective and cheapest treatment for terminal kidney failure. The transplantation programme is limited by the shortage of organs from deceased donors, therefore in many countries and in Slovakia a complementary programme of kidney transplantation from living donors has been established for years. Until recently, in addition to a negative cross-examination, an important condition for kidney transplantation was compatibility in the ABO system, but the development of elimination methods ensuring the removal of specific isoagglutinins and the availability of immunomodulatory and biologic drugs affecting the production of antibodies have made it possible to overcome the ABO barrier and safely transplant kidneys from ABO incompatible living donors. These transplantations offer hope, especially to those patients who have an ABO incompatible donor but have failed a kidney exchange program. We present a case of the first ABO incompatible living donor kidney transplantation in Slovakia, where a patient with blood group O received a kidney from his father with blood group B after desensitization preparation. The chances of success in the kidney exchange programme in the Slovak database were minimal. The aim of this case report is to draw attention to ABO incompatible living donor transplantation, which have the potential to increase the number of living donor kidney transplantation, including pre-emptive transplantation, and to reduce the waiting time for kidney transplantation in patients who do not have a living donor.

An in silico simulation of the frequency of administering HLA-incompatible low titer group O whole blood units when the donor pool includes unscreened female donors.

As low titer group O whole blood (LTOWB) increases in popularity, blood centers are finding innovative ways of maintaining the supply. One potential way is collecting LTOWB from parous female donors without testing for HLA antibodies. This in silico simulation predicted the risk of an LTOWB unit containing an HLA antibody and the subsequent risk for an HLA-incompatible transfusion. An LTOWB blood bank with 1 million units was simulated consisting of male, nulliparous, and parous female donors. The proportion of each donor type was modeled after the sex distribution at US blood centers. The parity of female donors was calculated based on the average number of live births per female depending on her age. HLA-alloimmunization risk was determined by her parity status. The HLA haplotypes of the simulated recipients were derived from the 100 most common HLA haplotypes in the US National Marrow Registry Program database. The proportion of different race/ethnic groups in the US was used to simulate 100,000 LTOWB recipients to whom between 1 and 10 units were administered. Overall, the risk of an LTOWB unit containing at least one HLA antibody was 12.2% and the rate of receiving an HLA-incompatible unit was 21.3%. The risk of receiving an HLA-incompatible unit rose from 4.8% after receipt of one unit to 36.5% after 10 units. Blood collectors and hospitals should evaluate the potential TRALI risk against the benefit of a potentially expanded inventory of LTOWB before collecting plasma-containing products from non-HLA-tested parous female donors.

Long-Term Liver Machine Perfusion Preservation: A Review of Recent Advances, Benefits and Logistics.

The global shortage of suitable donor livers for transplantation has prompted efforts to expand the donor pool by using extended criteria donors. Machine preservation technology has shown promise in optimizing graft preservation and improving logistics. Additionally, it holds potential for organ repair, regeneration, therapeutic applications during extended preservation periods, and enhancing organ allocation. We conducted a comprehensive literature review using PubMed, Embase, and Web of Science databases. All studies published between January 1, 2022, and February 7, 2024, that described machine perfusion preservation of livers for more than 24 h were eligible for inclusion. The findings were synthesized in a narrative review format to highlight key benefits and advancements. We identified eleven studies from multiple research groups, employing various techniques, devices, and preservation durations. Perfusion durations ranged from 1 to 13 days, with notable variations in protocols for long-term preservation beyond 24 h. Viability was assessed during perfusion only. No livers were transplanted. Among the reviewed studies, the introduction of a dialysis system emerged as the most effective strategy for managing waste accumulation during long-term liver perfusion. Differences were also observed in hemodynamics, oxygenation, organ chambers, supplemental regimens, and glycemic control. Over the past two years, substantial progress has been made in refining protocols for long-term liver machine perfusion, with significant advancements in waste management, enabling successful multi-day perfusions. While these developments are promising, further research is necessary to standardize and optimize long-term perfusion protocols, establishing a reliable platform for both organ preservation and therapeutic applications.

Promoting Inclusivity in Blood Donation: Public Health

The practice of blood donation supports community unity, as it brings all individuals on a common platform where they help each other and the health system in the mission to save human lives. Regardless of the wide scope and merits of blood donation in saving lives and improving health, it is a fact that many patients who are in need do not receive safe blood timely. As the existing pool of donors cannot meet the requirements of everyone, it is the need of the hour to appeal to and encourage a diverse group of blood donors to support the healthcare delivery system. Acknowledging the need to have a diverse pool of donors, we must promote inclusivity in blood donation and this will require a combination of multiple strategies. In conclusion, the availability of a diverse blood donor base makes it extremely useful for patients from different backgrounds by making the entire process compatible and safe. Many barriers have been identified that could limit the inclusivity in blood donation, and this will require a comprehensive approach to ensure that all communities are equally represented in the donor pool, ultimately leading to a more diverse and adequate blood supply.

Viability Assessment During Normothermic Machine Liver Perfusion: A Literature Review.

The discrepancy between donor organ availability and demand leads to a significant waiting-list dropout rate and mortality. Although quantitative tools such as the Donor Risk Index (DRI) help assess organ suitability, many potentially viable organs are still discarded due to the lack of universally accepted markers to predict post-transplant outcomes. Normothermic machine perfusion (NMP) offers a platform to assess viability before transplantation. Thus, livers considered unsuitable for transplantation based on the DRI can be evaluated and potentially transplanted. During NMP, various viability criteria have been proposed. These criteria are neither homogeneous nor consensual. In this review, we aimed to describe the viability criteria during NMP and evaluate their ability to predict hepatic graft function following transplantation. We conducted a PubMed search using the terms 'liver transplantation', 'normothermic machine perfusion' and 'assessment', including only English publications up to February 2024. Viability assessment during NMP includes multiple hepatocellular and cholangiocellular criteria. Lactate clearance and bile production are commonly used indicators, but their ability to predict post-transplant outcomes varies significantly. The predictive value of cholangiocellular criteria such as bile pH, bicarbonate and glucose levels remains under investigation. Novel markers, such as microRNAs and proteomic profiles, offer the potential to enhance graft evaluation accuracy and provide insights into the molecular mechanisms underlying liver viability. Combining perfusion parameters with biomarkers may improve the prediction of long-term graft survival. Future research should focus on standardising viability assessment protocols and exploring real-time biomarker evaluations, which could enhance transplantation outcomes and expand the donor pool.

Innovations to Expand the Liver Donor Pool

Innovations to Expand the Liver Donor Pool

Advances and Challenges of Thrombolytic Therapy for Donation After Circulatory Death Organs.

The demand for organ transplantation has exceeded the global supply of available organs. Donation after circulatory death (DCD) is considered an effective method to solve the disparity between the supply and demand of organs, by expanding the donor pool. However, DCD organs experience long-term damage caused by warm ischemia (WI) and microthrombosis caused by diffuse intravascular coagulation. Unfortunately, because of concerns about post-transplantation complications, most organs considered high-risk are discarded, resulting in wasted medical resources and economic losses. However, thrombolytic therapy before transplantation may dissolve microthrombosis in DCD organs, improve organ microcirculation, and increase organ use. Herein, we review the current status and potential value of thrombolytic therapy before DCD organ transplantation, summarize the progress of thrombolytic therapy for DCD organ transplantation according to preclinical and clinical research, and emphasize the heterogeneity and limitations of studies that have caused some controversies associated with this therapy. Overall, the role of thrombolytic therapy should not be overlooked. We anticipate that thrombolytic therapy combined with machine perfusion will provide an opportunity to improve inferior-quality DCD grafts, resulting in their becoming more widely available and safer for transplantation, thus solving the urgent problem of organ shortage.

From core to surface: Expanding the donor pool with Hepatitis B Surface antigen positive liver allografts.

From core to surface: Expanding the donor pool with Hepatitis B Surface antigen positive liver allografts.

Indications and recipient outcomes of adult left lobe living donor liver transplantation.

Adult left lobe living donor liver transplantation has long been practiced nearly exclusively in Japan. To overcome the potential risks of small-for-size syndrome and hepatic venous outflow obstruction associated with the use of left lobe grafts, center-specific countermeasures such as splenectomy, meticulous hepatic venous reconstruction, and inclusion of the caudate lobe have been implemented, resulting in short- and long-term results comparable with those of right lobe graft in high-volume centers. A recent systematic review and meta-analysis confirmed these observations; however, the indications and techniques of adult left lobe living donor liver transplantation have yet to be standardized. Recently, there is a growing momentum in the Western countries toward adult left lobe living donor liver transplantation to expand the donor pool in an era of severe organ scarcity and decrease waitlist mortality rates. The introduction of minimally invasive living-donor hepatectomy is expected to further facilitate the use of left lobe grafts.

Machine Perfusion Liver Preservation: Highlights From the International Liver Transplant Society 2024.

The 2024 International Liver Transplantation Society (ILTS) Congress, held in Houston, Texas, brought together a dynamic, multidisciplinary community of global experts to explore and discuss cutting-edge innovations and unmet needs in liver transplantation. Key themes included liver machine perfusion and donation after circulatory death (DCD), reflecting the ongoing effort to expand the donor pool and improve transplantation outcomes. Machine perfusion technologies, including normothermic machine perfusion (NMP), hypothermic oxygenated perfusion (HOPE), and normothermic regional perfusion (NRP) have demonstrated great promise in optimizing graft quality, mitigating ischemia-reperfusion injury, and enhancing the use of marginal and DCD liver grafts. At this year's congress a total of 63 abstracts on liver machine perfusion were presented. For this report we selected all orally presented abstracts highlighting advances in organ preservation, artificial intelligence, treatments during ex-situ perfusion including cellular therapy as well as new the use of new biomarkers. Preclinical highlights included the potential of long-term NMP to sustain and regenerate grafts during extended ex-situ preservation, spontaneous defatting of steatotic grafts during LT-NMP, the delivery of regulatory T cells to enable organ-level immunomodulation and the removal of damage-associated molecular patterns from porcine DCD livers during NMP. On the clinical side, key points included the progression of HOPE to IDEAL-D Stage 4 evidence, increased transplant volumes through the application of NMP, the cost-effectiveness of NMP as well as the utilization of very old DCD donors through NRP. Collectively, these advancements mark a transition toward dynamic, data-driven, and personalized transplantation strategies. Machine perfusion remains central to optimizing grafts, expanding the pool of organs suitable for transplantation enhancing access to liver transplantation and improving outcomes for liver transplant recipients worldwide.

P-2203. High Rate of False Positives in Military Blood Donors Screening Positive for Hepatitis C Virus

Abstract Background While the overall rates of Hepatitis C virus (HCV) in military populations are low, positive post-donation screening represents the second most common indication for post-donation infectious deferrals in military blood donors. All donors who screen positive are permanently deferred from blood donation, regardless of follow-up testing in clinical laboratories. There is limited data on the follow-up evaluation of these blood donors. This study describes the confirmatory testing, access to appropriate subspecialty care, and treatment of blood donors who screened positive for HCV at a large military blood bank. Methods All military blood donors between 2017-2023 at the Armed Service Blood Bank Center-San Antonio were screened for HCV by both antibody tests and nucleic acid tests, with positive antibody screening tests confirmed with an enzyme-linked immunosorbent assay (ELISA). Donors who screened positive had their medical charts reviewed to determine demographic information, follow-up evaluation, and treatment rates. On follow-up clinical diagnostic tests, patients with positive antibodies were determined to true positives (TP) and those with negative antibodies were determined to be FP. Results Of the 100,182 blood donors during the study period, 37 (0.04%) screened positive for HCV, of which follow-up information was available for 27 (73%). Of these 27, only 12 (44%) of donors were found to be TP. TP donors were more likely to be older (median 22 [20-29.5] vs. 20 [18-22], p=0.05) and have higher rates of positive nucleic acid testing (58% vs. 0%, p=0.001) after blood donation (Table 1). There was no difference in linkage to both primary and subspecialty care for TP and FP (Table 2). Of the TP, 7 (58%) were viremic, 3 (43%) of which received anti-viral therapy and 4 (57%) were administratively separated. Conclusion While HCV is one of the most common infectious reasons for military service members who donate blood to be deferred from future donations, most positive screenings were FP. Future efforts should be made to re-enter these patients with FP screening tests back into the donor pool. Disclosures All Authors: No reported disclosures

372. Impact of Updated 2020 Public Health Service Guidelines on Deceased Organ Donors and Transplant Recipients

Abstract Background New guidelines for assessing solid organ donors and recipients for Human Immunodeficiency Virus (HIV), Hepatitis B (HBV), and Hepatitis C (HCV) infection were published by the US Public Health Service (PHS) in 2020 and implemented into Organ Procurement and Transplantation Network (OPTN) policy on 3/1/21. Changes included a shorter risk criteria inclusionary timeframe and the removal of 4 risk criteria. Methods We analyzed OPTN deceased donor and transplant data 2 years pre-(3/1/19-2/28/21) and post-(3/1/21-3/1/23) implementation of the updated guidelines. For Kaplan-Meier survival analyses, the post- cohort included recipients transplanted before 1/1/23 to ensure recipients had at least 1 year follow-up plus a 3-month data lag. Utilization rates, defined as number of organs transplanted divided by number of available organs from donors with at least 1 organ recovered for the purpose of transplant, are shown for thoracic organs. Non-use rates, defined as number of organs recovered for the purpose of transplant but not transplanted divided by the total number of organs recovered for the purpose of transplant, are shown for abdominal organs. Results The proportion of donors considered to have PHS risk factors decreased by approximately 10% post-policy, both overall and by organ type (Fig. 1). There were no major differences pre- to post- in reported donor HIV, HCV or HBV NAT test results (Fig2. ). Post-policy, utilization rates for heart and lung for donors with risk factors were 34.9% and 17.5% respectively, compared to 34.3% and 20.0% pre-policy; while kidney and liver non-use rates for donors with risk factors were 20.3% and 8.2% respectively, compared to 17.2% and 7.9% pre-policy. There was no significant change in 1-year post-transplant patient survival for recipients who received organs from donors with PHS risk factors (Fig. 3). Conclusion Less restrictive PHS guidelines led to fewer donors being classified as having risk factors for disease transmission. Updated guidelines did not significantly affect donor infectious disease test results or post-transplant survival for recipients. Changes in donor organ utilization and non-use may be due to donor pool changes and/or overlapping policy implementations, and further investigation is warranted. Disclosures Lara A. Danziger-Isakov, MD, MPH, Aicuris: clinical research contract, paid to institutio|Ansun BioPharma: clinical research contract, paid to institution|Astellas: Advisor/Consultant|Astellas: clinical research contract, paid to institutio|Merck: clinical research contract, paid to institutio|Pfizer: Grant/Research Support|Takeda: clinical research contract, paid to institutio

P-2321. Role of the Transplant Infectious Disease Physician in Potential Donor Evaluation for Successful and Safe Abdominal Transplantation

Abstract Background Preventing donor derived infections is critical in solid organ transplant medicine. However, to expand the donor pool, utilizing organs from donors with known infections or at risk of disease transmission with proper prophylaxis and/or treatments is necessary. The purpose of this study is to determine the efficacy and impact of robust transplant Infectious disease (TxID) evaluation for high-risk donors in solid organ transplant centers. Methods This is a retrospective study conducted at one of the largest solid organ transplant centers in the US. All electrical medical records regarding donor information and obtained interventions were retrospectively reviewed between June 2023, and March 2024. Results During study period, we performed 358 (250, 15, and 93 kidney, kidney-pancreas, and liver) transplants. At the time of organ offer, out of 4,579 total organ offers, 93(2.03%) TxID consultations occurred. The majority of TxID consults were to review positive culture (50/93, 53.8%) and abnormal imaging. TxID declined 19/93 (20.4%) cases due to high risk of infectious disease transmission such as active staphylococcal bacteremia or candidemia. Additional 44 cases were either declined due to other reasons or accepted in other centers. Finally, 30 cases were transplanted and out of those, 22 (73.3%) received prophylaxis. No donor derived infections were noted in those 30 cases. Of note, graft loss or death due to infection within 90 days post-transplant was seen in 10/250, 7/93, and 2/15 for kidney, kidney pancreas, and liver transplants respectively, and none of those cases developed donor derived disease. Conclusion Solid organ transplantation helps prolong and improve recipients’ quality of life. Risk assessment, prophylaxis, and monitoring makes it possible to safely accept donors who are considered high risk for infection transmission, while preventing donor derived infections. Early TxID consultation for those cases is crucial. Disclosures Yoichiro Natori, MD, Eurofin/Viracor: Honoraria|Nobel Pharma: Advisor/Consultant

Machine perfusion strategies in Liver Transplantation: A systematic review, pairwise, and network meta-analysis of randomized controlled trials.

Machine perfusion (MP), including hypothermic oxygenated machine perfusion (HOPE), dual HOPE, normothermic machine perfusion (NMP), NMP ischemia-free liver transplantation (NMP-ILT), and controlled oxygenated rewarming (COR), is increasingly being investigated to improve liver graft quality from extended criteria donors and donors after circulatory death and expand the donor pool. This network meta-analysis investigates the comparative efficacy and safety of various liver MP strategies versus traditional static cold storage (SCS). We searched PubMed, Scopus, Web of Science, and Cochrane Controlled Register of Trials for randomized controlled trials (RCTs) comparing liver transplantation (LT) outcomes between SCS and MP techniques. The primary outcome was the incidence of early allograft dysfunction (EAD). Secondary endpoints included 1-year graft survival, the incidence of graft failure/loss, post-reperfusion syndrome, biliary complications, the need for renal replacement therapy (RRT), graft-related patient mortality, and the length of intensive care unit (ICU) and hospital stay. R-software was used to conduct a network meta-analysis using a frequentist framework. CRD42024549254. We included 12 RCTs involving 1,628 patients undergoing LT (801 in the liver MP groups and 832 in the SCS group). Compared to SCS, HOPE/dHOPE, but not other MP strategies, was associated with a significantly lower risk of EAD (RR: 0.53, 95% CI [0.37, 0.74], p=0.0002), improved 1-year graft survival rate (RR: 1.07, 95% CI [1.01, 1.14], p=0.02), decreased graft failure/loss (RR: 0.38, 95% CI [0.16, 0.90], p=0.03), and reduced the risk of biliary complications (RR: 0.52, 95% CI [0.43, 0.75], p < 0.0001). Compared to SCS, NMP (RR: 0.49, 95% CI [0.24, 0.96] and NMP-ILT (RR: 0.15, 95% CI [0.04, 0.57], both significantly reduced the risk of post-perfusion syndrome. There is no difference between SCS and MP groups in the risk of RRT, graft-related patient mortality, and ICU and hospital stay length. Our meta-analysis showed that HOPE/dual-HOPE is a promising alternative to SCS for donor liver preservation. These new techniques can help expand the donor pool with similar or even better post-LT outcomes.

Normothermic Machine Perfusion in Orphan Liver Graft Viability Assessment

Background: Liver transplantation constitutes a well-established treatment for patients with end-stage liver disease and selected hepatic malignancies. The introduction of normothermic machine perfusion (NMP) offers a platform for both extracorporeal organ maintenance and viability assessment, especially for organs with suspicious malfunction. These organs, discarded by the majority of transplant centers (so-called ‘orphan livers’), may help to safely expand the donor pool thanks to pre-transplant appraisal; Methods: We identified all grafts undergoing normothermic ma-chine perfusions performed in the Department of General, Transplant, and Liver Surgery between December 2022 and August 2023. Their perfusion characteristics and immediate postoperative periods, as well as complications that occurred in the 90-day postoperative periods, were analyzed; Results: There were eight orphan liver grafts that underwent NMP in our Department. Postoperative complications occurring in patients receiving grafts after NMP did not seem associated with the procedure. One patient required laparotomy within the 90-day postoperative period due to biliary fistula and underwent bile duct stenting due to both fistula and nonanastomotic stricture. In one patient we observed the occurrence of anastomotic biliary stricture more than 90 days after LTx; Conclusions: NMP allows for the viability assessment of grafts with suspicious prepreservation malfunction. Some of these organs may help to expand the donor pool.

Donors With Previous Malignancy: When Is It Safe to Proceed With Organ Transplantation?

The growing number of organ donors in the United States, from 14,011 in 2012 to 21,374 in 2022, highlights progress in addressing the critical issue of organ shortages. However, the demand remains high, with 17 patients dying daily while on the waiting list. As of August 2023, over 103,544 individuals are awaiting transplants, predominantly for kidneys (85.7%). To expand the donor pool, the inclusion of elderly donors, including those with a history of malignancies, is increasingly considered. In 2022, 7% of all donors were aged 65 and above, despite the complexities their medical histories may introduce, particularly the risk of donor-transmitted cancer (DTC). This review examines the challenges and potential benefits of using donors with known malignancy histories, balancing the risks of DTC against the urgency for transplants. A critical analysis is presented on current knowledge and the decision-making processes that consider cancer types, stages, and patient survival outcomes. The goal is to identify missed opportunities and improve strategies for safe and effective organ transplantation from this donor demographic.

Exploring auxiliary liver transplantation in the era of transplant oncology - A proposal for a new liver splitting program (ALERT-50).

Total hepatectomy and liver transplantation has emerged as a game-changing strategy in the treatment of several liver-confined primary or metastatic tumors, opening the new era of transplant oncology. However, the expansion of indications is going to worsen the chronic scarcity of organs, and new strategies are needed to enlarge the donor pool. A possible source of organs could be developing split liver transplantation (SLT) programs. We propose to refer donors aged 18-50 years unsuitable for pediatric patients and donors aged 50-60 years for split evaluation. This will generate new small left lateral grafts that can be used for RAPID procedures, based on a national waiting list specifically for non-HCC oncologic patients. Centralized imaging review will streamline the donor-recipient matching process and address organizational challenges. Additionally, adopting an ex-situ splitting technique during hypothermic oxygenated machine perfusion could further enhance logistical efficiency and improve graft viability. The proposed protocol (ALERT 50) will therefore promote the development of oncologic indications without affecting the standard waiting list and without competing with urgent or pediatric patients.

Friend or Foe? Safety and Efficacy of Hepatitis B Viremic Solid Organ Allograft into Seronegative Recipients.

Long-term outcomes of HBV nucleic acid test (NAT)-positive (+) allograft use in seronegative liver transplant (LT) and kidney transplant (KT) recipients remains unknown despite being incorporated into practice by select centers. This study compares long-term outcomes between HBV NAT+ and NAT-negative (-) allografts in seronegative recipients. All recipients of an HBV core antibody-positive (HBcAb+) LT or KT were prospectively evaluated at a single transplant center from 6/2015-3/2023 and compared by NAT status. Study endpoints were post-transplant viremia, patient, and graft survival. 144 HBcAb+ LT and 220 HBcAb+ KT were performed including 57 (39.6%) NAT+ LT's and 123 (55.9%) NAT+ KT's with a median follow-up of 36 months. 14.8% of NAT+ and 3.5% of NAT- LTs experienced post-transplant viremia (p=0.004). At the time of last follow-up, 100% of NAT+ and 98.9% of NAT- LT recipients had undetectable HBV DNA (p=0.31). 4.1% of NAT+ and 6.2% of NAT- KTs experienced post-transplant viremia (p=0.12). At the time of last follow-up, 100% of NAT+ and 96.9% of NAT- KT recipients had undetectable HBV DNA (p=0.85). LT and KT patient and graft survival were not different between groups (p>0.05). With close surveillance, HBV seronegative recipients transplanted with NAT+ allografts can develop viremia which can be cleared with antiviral therapy. This is the first and largest single-center study reporting longer-term experience with HBV NAT+ allografts in seronegative recipients demonstrating the safe expansion of the donor pool.

Predictors of Nonutilization of Ex Vivo Perfused Donor Heart Allografts

Despite the development of novel procurement technologies, an imbalance remains between the demand for and the availability of donor hearts. We aimed to identify donor characteristics predictive of nonutilization of hearts supported by ex vivo perfusion. A national database was used to identify ex vivo perfused hearts before September 30, 2023. Donors were stratified into cohorts of “Used” and “Discarded” based on final allocation. Logistic regressions were developed to identify predictors of nonutilization in both the ex vivo and non-ex vivo perfused hearts. Of 1,393 hearts supported with ex vivo perfusion, 154 (11%) were unused. Unused donors were older and had more diabetes and hypertension (p &lt; 0.05). By multivariable logistic regression, reduced ejection fraction (7.10 [3.19–15.77], p &lt; 0.001), coronary artery disease (6.27 [1.15–34.30], p = 0.034), and advanced age (3.25 [2.02–5.21], p &lt; 0.001) were predictors of discard. Elevated body mass and prolonged ischemic times were only predictive of discard in the non-ex vivo perfused cohort. Among procured donor hearts supported by ex vivo perfusion, poor heart function, and donor comorbidities were identified as predictors of nonutilization. Increased appreciation for the role of these variables on post-transplantation outcomes will allow for the development of cost-effective strategies to expand the donor pool.

Decellularized Liver Matrices for Expanding the Donor Pool-An Evaluation of Existing Protocols and Future Trends.

Liver transplantation is the only curative option for end-stage liver disease and is necessary for an increasing number of patients with advanced primary or secondary liver cancer. Many patient groups can benefit from this treatment, however the shortage of liver grafts remains an unsolved problem. Liver bioengineering offers a promising method for expanding the donor pool through the production of acellular scaffolds that can be seeded with recipient cells. Decellularization protocols involve the removal of cells using various chemical, physical, and enzymatic steps to create a collagenous network that provides support for introduced cells and future vascular and biliary beds. However, the removal of the cells causes varying degrees of matrix damage, that can affect cell seeding and future organ performance. The main objective of this review is to present the existing techniques of producing decellularized livers, with an emphasis on the assessment and definition of acellularity. Decellularization agents are discussed, and the standard process of acellular matrix production is evaluated. We also introduce the concept of the stepwise assessment of the matrix during decellularization through decellularization cycles. This method may lead to shorter detergent exposure times and less scaffold damage. The introduction of apoptosis induction in the field of organ engineering may provide a valuable alternative to existing long perfusion protocols, which lead to significant matrix damage. A thorough understanding of the decellularization process and the action of the various factors influencing the final composition of the scaffold is essential to produce a biocompatible matrix, which can be the basis for further studies regarding recellularization and retransplantation.