Consensus Statement: Technical Standards for Thoracoabdominal Normothermic Regional Perfusion.

BACKGROUND: Thoracoabdominal normothermic regional perfusion (TA-NRP) has emerged as a powerful technique for optimizing organ procurement from donation after circulatory death donors. Despite its rapid adoption, standardized guidelines for TA-NRP implementation are lacking, prompting the need for consensus recommendations to ensure safe and effective utilization of this technique. METHODS: A working group composed of members from The American Society of Transplant Surgeons, The International Society of Heart and Lung Transplantation, The Society of Thoracic Surgeons, and The American Association for Thoracic Surgery was convened to develop technical guidelines for TA-NRP. The group systematically reviewed existing literature, consensus statements, and expert opinions to identify key areas requiring standardization, including predonation evaluation, intraoperative management, postdonation procedures, and future research directions. RESULTS: The working group formulated recommendations encompassing donor evaluation and selection criteria, premortem testing and therapeutic interventions, communication protocols, and procedural guidelines for TA-NRP implementation. These recommendations aim to facilitate coordination among transplant teams, minimize variability in practice, and promote transparency and accountability throughout the TA-NRP process. CONCLUSIONS: The consensus guidelines presented herein serve as a comprehensive framework for the successful and ethical implementation of TA-NRP programs in organ procurement from donation after circulatory death donors. By providing standardized recommendations and addressing areas of uncertainty, these guidelines aim to enhance the quality, safety, and efficiency of TA-NRP procedures, ultimately contributing to improved outcomes for transplant recipients.

Phase I clinical trial of the feasibility and safety of direct peritoneal resuscitation in liver transplantation.

BACKGROUND: Direct peritoneal resuscitation (DPR) is associated with improved outcomes in trauma. Animal models suggest DPR has favorable effects on the liver. We sought to evaluate its safety and assess for improved outcomes in liver transplantation (LT). METHODS: LT patients with renal dysfunction and/or obesity were enrolled in a phase-I clinical trial. DPR lasted 8-24 â€‹h depending on postoperative disposition. Primary outcome was percent of patients completing DPR. Secondary outcomes evaluated complications. Controls with either obesity (control-1) or both risk factors (obesity â€‹+ â€‹renal dysfunction, control-2) were analyzed. RESULTS: Fifteen patients were enrolled (seven with both criteria and eight with obesity alone). DPR was completed in 87 â€‹% of patients, with one meeting stopping criteria. Controls included 45 (control-1) and 24 (control-2) patients. Return to operating room, graft loss, and late infections were lower with DPR. CONCLUSION: DPR appears to be safe in closed abdomens following LT, warranting a follow-up phase-II trial to assess efficacy.

Consensus Statement: Technical Standards for Thoracoabdominal Normothermic Regional Perfusion.

BACKGROUND: Thoracoabdominal normothermic regional perfusion (TA-NRP) has emerged as a powerful technique for optimizing organ procurement from donation after circulatory death donors. Despite its rapid adoption, standardized guidelines for TA-NRP implementation are lacking, prompting the need for consensus recommendations to ensure safe and effective utilization of this technique. METHODS: A working group composed of members from The American Society of Transplant Surgeons, The International Society of Heart and Lung Transplantation, The Society of Thoracic Surgeons, and The American Association for Thoracic Surgery was convened to develop technical guidelines for TA-NRP. The group systematically reviewed existing literature, consensus statements, and expert opinions to identify key areas requiring standardization, including predonation evaluation, intraoperative management, postdonation procedures, and future research directions. RESULTS: The working group formulated recommendations encompassing donor evaluation and selection criteria, premortem testing and therapeutic interventions, communication protocols, and procedural guidelines for TA-NRP implementation. These recommendations aim to facilitate coordination among transplant teams, minimize variability in practice, and promote transparency and accountability throughout the TA-NRP process. CONCLUSIONS: The consensus guidelines presented herein serve as a comprehensive framework for the successful and ethical implementation of TA-NRP programs in organ procurement from donation after circulatory death donors. By providing standardized recommendations and addressing areas of uncertainty, these guidelines aim to enhance the quality, safety, and efficiency of TA-NRP procedures, ultimately contributing to improved outcomes for transplant recipients.

American Society of Transplant Surgeons Normothermic Regional Perfusion Standards: Ethical, Legal, and Operational Conformance.

BACKGROUND: The American Society of Transplant Surgeons convened a multidisciplinary working group to address operational, ethical, and legal considerations surrounding normothermic regional perfusion (NRP) procurement. METHODS: The working group, comprising members from American Society of Transplant Surgeons and AST across various disciplines including transplant surgery, hepatology, critical care, and bioethics, collaborated to formulate recommendations and guidance for NRP procurement. RESULTS: The following topics were identified by the group as essential standards that need to be addressed for ethical, legal, and operational conformance: terminology; conceptualization of death in the context of NRP; and communication, logistics, and training and competency. CONCLUSIONS: Fourteen recommendations that support the ethical and legal acceptability of NRP in the United States and set expectations for the conduct of NRP procedures are provided.

Survival following liver transplantation: A population-based nested case-control study.

BACKGROUND: Liver transplantation is the gold standard treatment for end-stage liver disease. This study evaluates post-transplantation survival compared with the general population by quantifying standardized mortality ratios in a nested case-control study. METHODS: Controls were noninstitutionalized United States inhabitants from the National Longitudinal Mortality Study. Cases underwent liver transplantation from 1990 to 2007 identified through the Organ Procurement and Transplantation Network database. Propensity matching (5:1, nearest neighbor, caliper 0.1) identified controls based on age, sex, race, and state. The primary endpoint was 10-year survival. RESULTS: 62,788 cases were matched to 313,381 controls. The overall standardized mortality ratio was 2.46 (95% CI â€‹= â€‹2.44-2.48). The standardized mortality ratio was higher for males (2.59 vs. 2.25) and Hispanic patients (4.80). Younger patients and those transplanted earlier (1990-1995) had higher standardized mortality ratios. CONCLUSIONS: Liver recipients have a standardized mortality ratio 2.46 times higher than the general population. Long-term mortality has declined over time.

Toxicology, pharmacokinetics, and immunogenicity studies of CCR4-IL2 bispecific immunotoxin in rats and minipigs.

We have developed a diphtheria toxin-based recombinant human CCR4-IL2 bispecific immunotoxin (CCR4-IL2-IT) for targeted therapy of cutaneous T-cell lymphoma (CTCL). CCR4-IL2-IT demonstrated superior efficacy in an immunodeficient mouse CTCL model. Recently, we have compared the in vivo efficacy of CCR4-IL2-IT versus Brentuximab (FDA approved leading drug in CTCL market) in the same immunodeficient mouse CTCL model. The comparison demonstrated that CCR4-IL2-IT was significantly more effective than Brentuximab. In this study, we have performed non-GLP (Good Laboratory Practice) toxicology, pharmacokinetics, immunogenicity studies of CCR4-IL2-IT in both rats and minipigs. CCR4-IL2-IT demonstrated excellent safety profiles in both rats and minipigs. The maximum tolerated dose of CCR4-IL2-IT was determined as 0.4 mg/kg in both rats and minipigs. Complete blood count and chemistry analysis did not show significant difference for all measured parameters between the blood samples of pre-injection versus post-injection from the five-day toxicology studies of CCT4-IL2-IT in both rats and minipigs. Histology analysis did not show difference between the PBS treatment group versus CCR4-IL2-IT treatment group at 50 µg/kg in both rats and minipigs. The half-life of CCR4-IL2-IT was determined as about 45 min in rats and 30 min in minipigs. The antibodies against CCR4-IL2-IT were detected in about two weeks after CCR4-IL2-IT treatment. CCR4-IL2-IT did not induce cytokine release syndrome in a peripheral blood mononuclear cell derived humanized mouse model. The depletion of CCR4+ cell and CD25+ cell (two target cell populations of CCR4-IL2-IT) was observed in minipigs. The excellent safety profile promoted us to further develop CCR4-IL2-IT towards clinical trials.

Living Donor Liver Transplantation for Hepatocellular Carcinoma Within and Outside Traditional Selection Criteria: A Multicentric North American Experience.

OBJECTIVE: To evaluate long-term oncologic outcomes of patients post-living donor liver transplantation (LDLT) within and outside standard transplantation selection criteria and the added value of the incorporation of the New York-California (NYCA) score. BACKGROUND: LDLT offers an opportunity to decrease the liver transplantation waitlist, reduce waitlist mortality, and expand selection criteria for patients with hepatocellular carcinoma (HCC). METHODS: Primary adult LDLT recipients between October 1999 and August 2019 were identified from a multicenter cohort of 12 North American centers. Posttransplantation and recurrence-free survival were evaluated using the Kaplan-Meier method. RESULTS: Three hundred sixty LDLTs were identified. Patients within Milan criteria (MC) at transplantation had a 1, 5, and 10-year posttransplantation survival of 90.9%, 78.5%, and 64.1% versus outside MC 90.4%, 68.6%, and 57.7% ( P = 0.20), respectively. For patients within the University of California San Francisco (UCSF) criteria, respective posttransplantation survival was 90.6%, 77.8%, and 65.0%, versus outside UCSF 92.1%, 63.8%, and 45.8% ( P = 0.08). Fifty-three (83%) patients classified as outside MC at transplantation would have been classified as either low or acceptable risk with the NYCA score. These patients had a 5-year overall survival of 72.2%. Similarly, 28(80%) patients classified as outside UCSF at transplantation would have been classified as a low or acceptable risk with a 5-year overall survival of 65.3%. CONCLUSIONS: Long-term survival is excellent for patients with HCC undergoing LDLT within and outside selection criteria, exceeding the minimum recommended 5-year rate of 60% proposed by consensus guidelines. The NYCA categorization offers insight into identifying a substantial proportion of patients with HCC outside the MC and the UCSF criteria who still achieve similar post-LDLT outcomes as patients within the criteria.

Early predictors of prolonged intensive care utilization following liver transplantation.

INTRODUCTION: Creatinine, bilirubin, and fibrinolysis resistance are associated with multi-organ dysfunction and likely risk factors for prolonged intensive care unit (pICU) stay following liver transplantation (LT). We hypothesize postoperative day-1 (POD-1) labs will predict pICU. METHODS: LT recipients had clinical laboratories and viscoelastic testing with tissue plasminogen activator thrombelastography (tPA TEG) to quantify fibrinolysis resistance (LY30) on POD-1. pICU was defined as one week or longer in the ICU. Logistic regression was used to identify the relationship between POD-1 labs and pICU. RESULTS: Of 304 patients, 50% went to the ICU, with 15% experiencing pICU. Elevated creatinine (OR 6.6, P â€‹< â€‹0.001) and low tPA TEG LY30 (OR 3.7, P â€‹= â€‹0.004) were independent predictors of pICU after controlling for other risk factors. A 9-fold increase in the rate of 90-day graft loss (19% vs 2% p â€‹< â€‹0.001) was observed patients who had these risk factors for pICU. CONCLUSION: Elevated creatine and fibrinolysis resistance are associated with pICU and poor outcomes following LT.

The in-vitro influence of urea concentration on thromboelastrography in patients with and without end stage renal disease.

BACKGROUND: End stage renal disease (ESRD) is associated with platelet dysfunction but also thromboembolic complications. The specific role of increased blood urea nitrogen (BUN) on coagulation is unclear. We aimed to characterize thromboelastography (TEG) parameters from males and females with ESRD and normal kidney function and evaluate if exogenous urea in vitro reproduced those TEG differences. METHODS: We collected blood samples from 20 living kidney donors and 20 kidney recipients. TEG was performed without and with two increasing urea concentrations in vitro. TEG parameters were compared between recipients and donors. RESULTS: Blood from kidney recipients showed baseline increased maximum amplitude (MA) and shortened time to maximum amplitude (TMA) compared to donors. These differences were not confirmed in females. In all patients, BUN was inversely correlated with TMA (r = -0.342; p = 0.031). In males, BUN and creatinine concentrations showed a direct correlation with MA (0.583; p = 0.007) and an inverse correlation with TMA (r = -0.520; p = 0.019). Urea in vitro decreased R-time (p = 0.005) and increased LY30 (p = 0.009) in donors but not recipients. CONCLUSIONS: ESRD is associated with increased MA and decreased TMA on TEG. No change in MA was observed with increasing urea concentrations in vitro. Gender-specific variability in TEG parameters were observed.

CCR4-IL2 bispecific immunotoxin is more effective than brentuximab for targeted therapy of cutaneous T-cell lymphoma in a mouse CTCL model.

Cutaneous T-cell lymphoma (CTCL) encompasses two main subtypes: mycosis fungoides and Sezary syndrome. Global response rates for the systemic treatment of mycosis fungoides and Sezary syndrome are approximately 30%, and none of these treatments are thought to be curative. C-C chemokine receptor type 4 (CCR4) and CD25 are encouraging targets for the treatment of CTCL and are individually targeted by mogamulizumab and denileukin diftitox, respectively. We developed a novel CCR4-IL2 bispecific immunotoxin (CCR4-IL2 IT) targeting both CCR4 and CD25. CCR4-IL2 IT demonstrated superior efficacy against CCR4+ CD25+ CD30+ CTCL in an immunodeficient NSG mouse tumor model. Investigative New Drug-enabling studies of CCR4-IL2 IT are ongoing, including Good Manufacturing Practice production and toxicology studies. In this study, we compared the in vivo efficacy of CCR4-IL2 IT versus the US Food and Drug Administration-approved drug, brentuximab, using an immunodeficient mouse CTCL model. We demonstrated that CCR4-IL2 IT was significantly more effective in prolonging survival than brentuximab, and combination treatment of CCR4-IL2 IT and brentuximab was more effective than brentuximab or CCR4-IL2 IT alone in an immunodeficient NSG mouse CTCL model. Thus, CCR4-IL2 IT is a promising novel therapeutic drug candidate for CTCL treatment.

Reassessing the survival benefit of deceased donor liver transplantation: retrospective cohort study.

INTRODUCTION: Currently in the United States, deceased donor liver transplant (DDLT) allocation priority is based on the model for end-stage liver disease including sodium (MELD-Na) score. The United Network for organ sharing's 'Share-15' policy states that candidates with MELD-Na scores of 15 or greater have priority to receive local organ offers compared to candidates with lower MELD-Na scores. Since the inception of this policy, major changes in the primary etiologies of end-stage liver disease have occurred and previous assumptions need to be recalibrated. METHODS: The authors retrospectively analyzed the Scientific Registry of Transplant Recipients database between 2012 and 2021 to determine life years saved by DDLT at each interval of MELD-Na score and the time-to-equal risk and time-to-equal survival versus remaining on the waitlist. The authors stratified our analysis by MELD exception points, primary disease etiology, and MELD score. RESULTS: On aggregate, compared to remaining on the waitlist, a significant 1-year survival advantage of DDLT at MELD-Na scores as low as 12 was found. The median life years saved at this score after a liver transplant was estimated to be greater than 9 years. While the total life years saved were comparable across all MELD-Na scores, the time-to-equal risk and time-to-equal survival decreased exponentially as MELD-Na scores increased. CONCLUSION: Herein, the authors challenge the perception as to the timing of DDLT and when that benefit occurs. The national liver allocation policy is transitioning to a continuous distribution framework and these data will be instrumental to defining the attributes of the continuos allocation score.

Systematic review and meta-analysis of open versus laparoscopy-assisted versus pure laparoscopic versus robotic living donor hepatectomy.

The value of minimally invasive approaches for living donor hepatectomy remains unclear. Our aim was to compare the donor outcomes after open versus laparoscopy-assisted versus pure laparoscopic versus robotic living donor hepatectomy (OLDH vs. LALDH vs. PLLDH vs. RLDH). A systematic literature review of the MEDLINE, Cochrane Library, Embase, and Scopus databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement (up to December 8, 2021). Random-effects meta-analyses were performed separately for minor and major living donor hepatectomy. The risk of bias in nonrandomized studies was assessed using the Newcastle-Ottawa Scale. A total of 31 studies were included. There was no difference in donor outcomes after OLDH versus LALDH for major hepatectomy. However, PLLDH was associated with decreased estimated blood loss, length of stay (LOS), and overall complications versus OLDH for minor and major hepatectomy, but also with increased operative time for major hepatectomy. PLLDH was associated with decreased LOS versus LALDH for major hepatectomy. RLDH was associated with decreased LOS but with increased operative time versus OLDH for major hepatectomy. The scarcity of studies comparing RLDH versus LALDH/PLLDH did not allow us to meta-analyze donor outcomes for that comparison. There seems to be a marginal benefit in estimated blood loss and/or LOS in favor of PLLDH and RLDH. The complexity of these procedures limits them to transplant centers with high volume and experience. Future studies should investigate self-reported donor experience and the associated economic costs of these approaches.

Prevalence and progression of intraductal papillary mucinous neoplasms of the pancreas in solid organ transplant recipients: A systematic review.

Solid organ transplantation (SOT) recipients are known to carry an increased risk of malignancy because of long-term immunosuppression. However, the progression of intraductal papillary mucinous neoplasm of the pancreas (IPMN) in this population remains unclear. We performed a systematic review by searching PubMed, Embase, Scopus, and Google Scholar. All studies containing IPMNs in solid organ transplantation recipients were screened. We included 11 studies in our final analysis, totaling 274 patients with IPMNs of the 8213 SOT recipients. The prevalence from 8 studies was 4.7% (95% CI 2.4%-7.7%) in a random-effects model with median study periods of 24 to 220 months. The median rate for all progressions from 10 studies was 20% (range, 0%-88%) within 13 to 41 months of the median follow-up time. By utilizing the results of 3 case-control studies, the relative risk from a random-effects model for progression (worrisome features and high-risk stigmata) of IPMNs was 0.39 (95% CI 0.12-1.31). No adenocarcinoma derived from IPMN was reported in the included studies. Overall, this study indicates that the progression of pretransplant IPMN does not increase drastically compared with the general nontransplant population. However, considering the limited literature, further studies are required for confirmation.

EGF­IL2 bispecific and bivalent EGF fusion toxin efficacy against syngeneic head and neck cancer mouse models.

The epidermal growth factor receptor (EGFR) remains one of the best molecules for developing targeted therapy for multiple human malignancies, including head and neck squamous cell carcinoma (HNSCC). Small molecule inhibitors or antibodies targeting EGFR have been extensively developed in recent decades. Immunotoxin (IT)­based therapy, which combines cell surface binding ligands or antibodies with a peptide toxin, represents another cancer treatment option. A total of 3 diphtheria toxin (DT)­based fusion toxins that target human EGFR­monovalent EGFR IT (mono­EGF­IT), bivalent EGFR IT (bi­EGF­IT), and a bispecific IT targeting both EGFR and interleukin­2 receptor (bis­EGF/IL2­IT) were recently generated by the authors. Improved efficacy and reduced toxicity of bi­EGF­IT compared with mono­EGF­IT in immunocompromised HNSCC mouse models was reported. In the present study, bis­EGF/IL2­IT were generated using a unique DT­resistant yeast expression system and evaluated the in vitro and in vivo efficacy and toxicity of the 3 EGF­ITs in immunocompetent mice. The results demonstrated that while the three EGF­ITs had different efficacies in vitro and in vivo against HNSCC, bi­EGF­IT and bis­EGF/IL2­IT had significantly improved in vivo efficacy and remarkably less off­target toxicity compared with mono­EGF­IT. In addition, bis­EGF/IL2­IT was superior to bi­EGF­IT in reducing tumor size and prolonging survival in the metastatic model. These data suggested that targeting either the tumor immune microenvironment or enhancing the binding affinity could improve the efficacy of IT­based therapy. Bi­EGF­IT and bis­EGF/IL2­IT represent improved candidates for IT­based therapy for future clinical development.

Practice patterns of the medical evaluation of living liver donors in the United States.

Living donor liver transplantation (LDLT) can help address the growing organ shortage in the United States, yet little is known about the current practice patterns in the medical evaluation of living liver donors. We conducted a 131-question survey of all 53 active LDLT transplant programs in the United States to assess current LDLT practices. The response rate was 100%. Donor acceptance rate was 0.33 with an interquartile range of 0.33-0.54 across all centers. Areas of high intercenter agreement included minimum age cutoff of 18 years (73.6%) and the exclusion of those with greater than Class 1 obesity (body mass index, 30.0-34.9 m/kg 2 ) (88.4%). Diabetes mellitus was not an absolute exclusion at most centers (61.5%). Selective liver biopsies were performed for steatosis or iron overload on imaging (67.9% and 62.3%, respectively) or for elevated liver enzymes (60.4%). Steatohepatitis is considered an exclusion at most centers (84.9%). The most common hypercoagulable tests performed were factor V Leiden (FVL) (88.5%), protein C (73.1%), protein S (71.2%), antithrombin III (71.2%) and prothrombin gene mutation (65.4%). At 41.5% of centers, donors were allowed to proceed with donation with FVL heterozygote status. Most programs discontinue oral contraceptive pills at least 28 days prior to surgery. At most centers, the need for cardiovascular ischemic risk testing is based on age (73.6%) and the presence of one or more cardiac risk factors (68.0%). Defining areas of practice consensus and variation underscores the need for data generation to develop evidence-based guidance for the evaluation and risk assessment of living liver donors.

Viscoelastic Management of Coagulopathy during the Perioperative Period of Liver Transplantation.

Viscoelastic testing (VET) in liver transplantation (LT) has been used since its origin, in combination with standard laboratory testing (SLT). There are only a few, small, randomized controlled trials that demonstrated a reduction in transfusion rates using VET to guide coagulation management. Retrospective analyses contrasting VET to SLT have demonstrated mixed results, with a recent concern for overtreatment and the increase in postoperative thrombotic events. An oversight of many studies evaluating VET in LT is a single protocol that does not address the different phases of surgery, in addition to pre- and postoperative management. Furthermore, the coagulation spectrum of patients entering and exiting the operating room is diverse, as these patients can have varying anatomic and physiologic risk factors for thrombosis. A single transfusion strategy for all is short sighted. VET in combination with SLT creates the opportunity for personalized resuscitation in surgery which can address the many challenges in LT where patients are at a paradoxical risk for both life-threatening bleeding and clotting. With emerging data on the role of rebalanced coagulation in cirrhosis and hypercoagulability following LT, there are numerous potential roles in VET management of LT that have been unaddressed.

Choledochoduodenostomy continues to be a safe alternative for biliary reconstruction in deceased-donor liver transplantation.

Debate continues as to whether choledochoduodenostomy (CDD) can be used instead of Roux-en-Y choledochojejunostomy (CDJ) when duct-to-duct (DTD) is not an option. We hypothesized that CDD and CDJ had similar rates of complications. All deceased-donor liver transplantations from September 2011 to March 2020 were categorized by biliary reconstruction. Primary outcomes were bleeding, bile leak, anastomotic stricture, and cholangitis. Of the 1,086 patients, 812 (74.8%) received a DTD; 225 (20.7%) received a CDD; and 49 (4.5%) received a CDJ. Cholangitis was significantly higher in CDJ compared to DTD and CDD (26.5% vs 6% vs 13.8%, p < 0.0001). When controlling for significant confounders, CDJ had 10.2 higher odds of cholangitis (95% CI 4.4-23.2) compared to DTD, and 3.3 higher odds compared to CDD (95% CI 1.4-7.8). When compared to DTD, CDJ and CDD had significantly lower odds of stricture. CDD continues to be a safe alternative for biliary reconstruction in deceased-donor liver transplantation.

Low viscoelastic clot strength, platelet transfusions, and graft dysfunction are associated with persistent postoperative ascites following liver transplantation.

INTRODUCTION: High output, persistent ascites (PA) is a common complication following liver transplant (LT). Recent work has identified that platelets help maintain endothelial integrity and can decrease leakage in pathological states. We sought to assess the association of PA following LT with platelet count and platelet function. METHODS: Clot strength (MA) is a measure of platelet function and was quantified using thrombelastography (TEG). Total drain output following surgery was recorded in 24-h intervals during the same time frame as TEG. PA was considered >1 L on POD7, as that much output prohibits drain removal. RESULTS: 105 LT recipients with moderate or high volume preoperative ascites were prospectively enrolled. PA occurred in 28%. Platelet transfusions before and after surgery were associated with PA, in addition to POD5 TEG MA and POD5 MELD score. Patients with PA had a longer hospital length of stay and an increased rate of intraabdominal infections. CONCLUSION: Persistent ascites following liver transplant is relatively common and associated with platelet transfusions, low clot strength, and graft dysfunction.

Fibrinolysis resistance after liver transplant as a predictor of early infection.

BACKGROUND: Infection is a leading cause of morbidity in liver transplant (LT). Considering that the fibrinolytic system is altered in sepsis, we investigated the relationship between fibrinolysis resistance (FR) and post-transplant infection. METHODS: Fibrinolysis was quantified using thrombelastography (TEG) with the addition of tPA to quantify FR. FR was defined as LY30 = 0% and stratified as transient if present on POD1 or POD5 (tFR), persistent (pFR) if present on both, or no FR (nFR) if absent. RESULTS: 180 LT recipients were prospectively enrolled. 52 (29%) recipients developed infection. 72 had tFR; 37 had pFR; and 71 had nFR. Recipients with pFR had significantly greater incidence of infections (51% vs. 26% tFR vs. 20% nFR, p = 0.002). pFR was independently associated with increased odds of post-transplant infection (adjusted OR 3.39, p = 0.009). CONCLUSIONS: Persistent fibrinolysis resistance is associated with increased risk of post-transplant infection.

Survival Benefit of Living-Donor Liver Transplant.

Importance: Despite the acceptance of living-donor liver transplant (LDLT) as a lifesaving procedure for end-stage liver disease, it remains underused in the United States. Quantification of lifetime survival benefit and the Model for End-stage Liver Disease incorporating sodium levels (MELD-Na) score range at which benefit outweighs risk in LDLT is necessary to demonstrate its safety and effectiveness. Objective: To assess the survival benefit, life-years saved, and the MELD-Na score at which that survival benefit was obtained for individuals who received an LDLT compared with that for individuals who remained on the wait list. Design, Setting, and Participants: This case-control study was a retrospective, secondary analysis of the Scientific Registry of Transplant Recipients database of 119 275 US liver transplant candidates and recipients from January 1, 2012, to September 2, 2021. Liver transplant candidates aged 18 years or older who were assigned to the wait list (N = 116 455) or received LDLT (N = 2820) were included. Patients listed for retransplant or multiorgan transplant and those with prior kidney or liver transplants were excluded. Exposures: Living-donor liver transplant vs remaining on the wait list. Main Outcomes and Measures: The primary outcome of this study was life-years saved from receiving an LDLT. Secondary outcomes included 1-year relative mortality and risk, time to equal risk, time to equal survival, and the MELD-Na score at which that survival benefit was obtained for individuals who received an LDLT compared with that for individuals who remained on the wait list. MELD-Na score ranges from 6 to 40 and is well correlated with short-term survival. Higher MELD-Na scores (>20) are associated with an increased risk of death. Results: The mean (SD) age of the 119 275 study participants was 55.1 (11.2) years, 63% were male, 0.9% were American Indian or Alaska Native, 4.3% were Asian, 8.2% were Black or African American, 15.8% were Hispanic or Latino, 0.2% were Native Hawaiian or Other Pacific Islander, and 70.2% were White. Mortality risk and survival models confirmed a significant survival benefit for patients receiving an LDLT who had a MELD-Na score of 11 or higher (adjusted hazard ratio, 0.64 [95% CI, 0.47-0.88]; P = .006). Living-donor liver transplant recipients gained an additional 13 to 17 life-years compared with patients who never received an LDLT. Conclusions and Relevance: An LDLT is associated with a substantial survival benefit to patients with end-stage liver disease even at MELD-Na scores as low as 11. The findings of this study suggest that the life-years gained are comparable to or greater than those conferred by any other lifesaving procedure or by a deceased-donor liver transplant. This study's findings challenge current perceptions regarding when LDLT survival benefit occurs.