Normothermic machine perfusion for older transplant recipients.

INTRODUCTION: Elderly patients (≥65 years old) are increasingly undergoing liver transplantation and are more likely to be removed from the waitlist. Normothermic machine perfusion (NMP) holds promise in expanding the number of livers available for transplant and improving outcomes for marginal donors and recipients. We aimed to determine the impact of NMP on outcomes in elderly recipients at our institution and nationally using the UNOS database. METHODS: The use of NMP on outcomes in elderly recipients was reviewed using both the UNOS/SRTR database (2016-2022) and institutional data (2018-2020). Characteristics and clinical outcomes were compared between the NMP and static cold (control) groups within both populations. RESULTS: Nationally, using the UNOS/SRTR database, we identified 165 elderly recipients from 28 centers who received a liver allograft undergoing NMP and 4270 that underwent traditional cold static storage. NMP donors were older (48.3 vs. 43.4 years, p < 0.01), had similar rates of steatosis (8.5% vs 8.5%, p = 0.58), were more likely to be from a DCD (41.8% vs 12.3%, p < 0.01), and had a higher donor risk index (DRI; 1.70 vs. 1.60, p < 0.02). NMP recipients had similar age but had a lower MELD score at transplant (17.9 vs. 20.7, p = 0.01). Despite increased marginality of the donor graft, NMP recipients had similar allograft survival and decreased length of stay, even after accounting for recipient characteristics including MELD. Institutional data showed that 10 elderly recipients underwent NMP and 68 underwent cold static storage. At our institution, NMP recipients had a similar length of stay, rates of complications, and readmissions. CONCLUSIONS: NMP may mitigate donor risk factors that are relative contraindications for transplantation in elderly liver recipients, increasing the donor pool. The application of NMP in older recipients should be considered.

The impact of machine perfusion of the heart on warm ischemia time and organ yield in donation after circulatory death.

Successful normothermic machine perfusion of heart allografts (MPH) has led to rapid growth in transplantation of donation after circulatory death (DCD) heart allografts but has introduced complexity in the procurement process. This study examines the impact of MPH use in DCD procurements on warm ischemia time (WIT) and organ yield. DCD procurements from 2019 to 2020 were identified using the OPTN database. Procurements with and without the use of MPH were compared using propensity score matching. Observed to expected (O:E) yield ratios were calculated, where the expected values were obtained using the models developed by the Scientific Registry of Transplant Recipients. In total, 1237 DCD procurements met inclusion criteria (MPH: 109 and control: 1128). After PSM, no difference was found between groups in median total WIT (24.0 min vs. 24.0 min, p = .89), but the MPH group demonstrated shorter median operative WIT (circulatory arrest to cross-clamp; 8.7 min vs. 10.9 min, p = .003). The overall organ yield of DCD heart donors was observed to be 33% higher than expected (O:E 1.33; 95% CI: 1.22-1.45). Observed yield of non-heart organs was not significantly different from expected for liver, kidney, lung, and pancreas grafts. MPH use in DCD procurements does not lead to delays in WIT and does not negatively affect organ yield of other concurrently procured organs.

Simultaneous ex vivo normothermic preservation of liver and heart grafts from a donation after circulatory death donor.

Normothermic machine perfusion of organs is growing in popularity and has been used for both abdominal and thoracic organ preservation before transplantation. The use of normothermic machine perfusion for donation after cardiac death organs can reduce cold ischemia time and help prevent ischemia-related complications. We present a successful case of a donation after cardiac death procurement with both liver and heart allografts preserved by normothermic machine perfusion. Both allografts were perfused without complications and transplanted successfully. As the technology continues to become more prevalent, the situation described will become more commonplace, and we offer a view of the future in transplantation.

Optimal Timing of Administration of Direct-acting Antivirals for Patients With Hepatitis C-associated Hepatocellular Carcinoma Undergoing Liver Transplantation.

OBJECTIVE: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). SUMMARY OF BACKGROUND DATA: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate. METHODS: The United States HCC LT Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS). RESULTS: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01). CONCLUSIONS: The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.

Making Every Liver Count: Increased Transplant Yield of Donor Livers Through Normothermic Machine Perfusion.

OBJECTIVE: Normothermic machine perfusion (NMP) enables optimized ex-vivo preservation of a donor liver in a normal physiologic state. The impact of this emerging technology on donor liver utilization has yet to be assessed. SUMMARY BACKGROUND DATA: NMP of the donor liver and ex-vivo enhancement of its function has been envisioned for decades, however only with recent technological advances have devices been suitable for transition to clinical practice. The present study examines the effect NMP on liver utilization in the United States. METHODS: The United Network for Organ Sharing database was queried to identify deceased donor livers procured from 2016 to 2019 (n = 30596). Donor livers were divided by preservation method: standard cold-static preservation (COLD, n = 30,368) versus NMP (n = 228). Donor and recipient risk factors, liver disposition, and discard reasons were analyzed. The primary outcome was liver discard rate between 2 groups. RESULTS: A total of 4037 livers were discarded. The NMP group had a 3.5% discard rate versus 13.3% in the COLD group (P < 0.001), and this was despite NMP donors being older (47.7 vs 39.5 years, P < 0.0001), more frequently donation after cardiac death (DCD) (18% vs 7%, P < 0.001), and having a greater donor risk index (1.6 vs 1.5, P < 0.05). The most common reasons for liver discard in the COLD group were biopsy findings (38%), DCD warm ischemic time (11%), and prolonged preservation time (10%). Survival analysis, following propensity score matching, found no significant difference in 1-year overall survival between recipients of NMP versus COLD livers. CONCLUSIONS: NMP reduces the discard rate of procured livers despite its use in donors traditionally considered of more marginal quality. NMP maintains excellent graft and patient survival. Broader application of NMP technology holds the potential to generate a significant number of additional liver grafts for transplantation every year, thus greatly reducing the nationwide disparity between supply and demand.

The role of machine perfusion in liver xenotransplantation.

PURPOSE OF REVIEW: To review the role of machine perfusion in advancing the study and clinical application of liver xenotransplantation to liver transplantation. RECENT FINDINGS: Recent multicenter trial has shown the benefits of normothermic machine perfusion (NMP) in the assessment and selection of suitable allografts for liver transplantation, especially marginal liver allografts. Advances in ex-vivo therapeutic intervention with proof-of-concept studies demonstrating successful ex-vivo genetic modification of donor allografts and blockade of gene expression with siRNA. SUMMARY: Xenotransplantation and NMP are two of the most exciting and eagerly anticipated technologies in organ transplantation. Since the emergence of clinical transplantation, clinicians and researchers have attempted to manipulate xenografts for clinical use or to develop devices that could provide physiologic support of donor organs ex vivo. The past decade has seen significant progress in NMP with recent emergence of devices suitable for use in clinical practice. Following discovery of novel gene-editing techniques, xenotransplantation has also developed rapidly with encouraging outcomes in preclinical studies. Xenotransplantation is now currently poised to advance into the clinical realm. NMP can not only assist in the development of other novel technologies by providing a unique environment to safely study organ function and assess organ suitability but may also improve outcomes following hepatic xenotransplantation. In this review, we describe the current use of NMP in xenotransplantation research and also discuss the potential roles for NMP in xenotransplantation research and future clinical practice.

No Stone Left Unturned: Utilization of an Organ Procurement Organization Donor Surgeon at Procurement Reduces Discards of Marginal Liver Allografts.

BACKGROUND: The recent trend of organ procurement organizations (OPOs) employing independent surgeons for organ procurement has been developed with the goal of improving the supply of suitable organs for transplantation. We investigated the effects that the addition of an OPO-employed, organ-procurement specialist has on liver allograft discard rate, marginal organ utilization, and graft survival. METHODS: Organ Procurement and Transplant Network and OPO data were retrospectively studied between April 1, 2014' and July 31, 2019' within the Southwest Transplant Alliance donor service area. Liver procurements with an OPO-surgeon present (OPO-Present) were compared to those without the involvement of an OPO surgeon (OPO-Absent). Donor and recipient characteristics as well as outcomes were analyzed across groups using propensity score matching. RESULTS: In total 869 OPO-Present liver allografts had similar rates of discard (5.2%) compared to 771 OPO-Absent livers (5.8%). However, after adjusting for donor risk, OPO-Present livers had a lower propensity of discard compared to OPO-Absent (3.4% versus 7.6%, P < 0.05). OPO-Present livers were more likely to be shared nationally (11.0% versus 4.8%, P < 0.001). Outcome analysis showed allograft survival of OPO-Present livers at 5 y was comparable to OPO-Absent livers (79.5% versus 80%, P = 0.34). CONCLUSIONS: The presence of an OPO surgeon was associated with decreased liver allograft discard and increased utilization of marginal donor organs. The OPO surgeon's presence represents a potential strategy to increase organ utilization nationally.

Enhanced recovery in liver transplantation: A value-based approach to complex surgical care.

BACKGROUND: Value-based healthcare focuses on improving outcomes relative to cost. We aimed to study the impact of an enhanced recovery pathway for liver transplant recipients on providing value. METHODS: In total, 379 liver recipients were identified: pre-enhanced recovery pathway (2017, n = 57) and post-enhanced recovery pathway (2018-2020, n = 322). The enhanced recovery pathway bundle was defined through multidisciplinary efforts and included optimal fluid management, end-of-case extubation, multimodal analgesia, and a standardized care pathway. Pre- and post-enhanced recovery pathway patients were compared with regard to extubation rates, lengths of stay, complications, readmissions, survival, and costs. RESULTS: Pre- and post-enhanced recovery pathway recipient model for end-stage liver disease score and balance of risk scores were similar, although post-enhanced recovery pathway recipients had a higher median donor risk index (1.55 vs 1.39, P = .003). End-of-case extubation rates were 78% post-enhanced recovery pathway (including 91% in 2020) versus 5% pre-enhanced recovery pathway, with post-enhanced recovery pathway patients having decreased median intraoperative transfusion requirements (1,500 vs 3,000 mL, P < .001). Post-enhanced recovery pathway recipients had shorter median intensive care unit (1.6 vs 2.3 days, P = .01) and hospital stays (5.4 vs 8.0 days, P < .001). Incidence of severe (Clavien-Dindo ≥3) complications during the index hospitalization were similar between pre-enhanced recovery pathway versus post-enhanced recovery pathway groups (33% vs 23%, P = .13), as were 30-day readmissions (26% vs 33%, P = .44) and 1-year survival (93.0% vs 94.5%, P = .58). The post-enhanced recovery pathway cohort demonstrated a significant reduction in median direct cost per case ($11,406; P < .001). CONCLUSION: Implementation of an enhanced recovery pathway in liver transplantation is feasible, safe, and effective in delivering value, even in the setting of complex surgical care.