The cost of lung transplantation in the United States: How high is too high?

Objectives: To identify patient and process factors that contribute to the high cost of lung transplantation (LTx) in the perioperative period, which may allow transplant centers to evaluate situations in which transplantation is most cost-effective to inform judicious resource allocation, avoid futile care, and reduce costs. Methods: The MarketScan Research databases were used to identify 582 privately insured patients undergoing single or bilateral LTx between 2013 and 2019. The patients were subdivided into groups by disease etiology using the United Network of Organ Sharing classification system. Multivariable generalized linear models using a gamma distribution with a log link were fit to examine the associations between the etiology of lung disease and costs during the index admission, 3 months before admission, and 3 months after discharge. Results: Our results indicate that the index admission contributed the most to the total transplantation costs compared to the 3 months before admission and after discharge. The regression-adjusted mean index hospitalization cost was 35% higher for patients with pulmonary vascular disease compared to those with obstructive lung disease ($527,156 vs $389,055). The use of extracorporeal membrane oxygenation, mechanical ventilation, and surgical complications in the post-transplantation period were associated with higher costs during the index admission. Surprisingly, age ≥55 was associated with lower costs during the index admission. Conclusions: This analysis identifies pivotal factors influencing the high cost of LTx, emphasizing the significant impact of the index admission, particularly for patients with pulmonary vascular disease. These insights offer transplant centers an opportunity to enhance cost-effectiveness through judicious resource allocation and service bundling, ultimately reducing overall transplantation costs.

Short-term outcomes after third-time lung transplantation: A single institution experience.

BACKGROUND: Reoperative lung transplantation (LTx) survival has improved over time such that a growing number of patients may present for third-time LTx (L3Tx). To understand the safety of L3Tx, we evaluated perioperative outcomes and 3-year survival after L3Tx at a high-volume US LTx center. METHODS: This retrospective study included all patients who underwent bilateral L3Tx at our institution. Using an optimal matching technique, a primary LTx (L1Tx) cohort was matched 1:2 and a second-time LTx (L2Tx) cohort 1:1. Recipient, operative, and donor characteristics, perioperative outcomes, and 3-year survival were compared among L1Tx, L2Tx, and L3Tx groups. RESULTS: Eleven L3Tx, 11 L2Tx, and 22 L1Tx recipients were included. Among L3Tx recipients, median age at transplant was 37 years and most (73%) had cystic fibrosis. L3Tx was performed median 6.0 and 10.6 years after L2Tx and L1Tx, respectively. Compared to L1Tx and L2Tx recipients, L3Tx recipients had greater intraoperative transfusion requirements, a higher incidence of postoperative complications, and a higher rate of unplanned reoperation. Rates of grade 3 primary graft dysfunction at 72 hours, extracorporeal membrane oxygenation at 72 hours, reintubation, and in-hospital mortality were similar among groups. There were no differences in 3-year patient (log-rank p = 0.61) or rejection-free survival (log-rank p = 0.34) after L1Tx, L2Tx, and L3Tx. CONCLUSIONS: At our institution, L3Tx was associated with similar perioperative outcomes and 3-year patient survival compared to L1Tx and L2Tx. L3Tx represents the only safe treatment option for patients with allograft failure after L2Tx; however, further investigation is needed to understand the long-term survival and durability of L3Tx.

Textbook Outcome: Definition and Analysis of a Novel Quality Measure in Lung Transplantation.

OBJECTIVE: To define textbook outcome (TO) for lung transplantation (LTx) using a contemporary cohort from a high-volume institution. SUMMARY BACKGROUND DATA: TO is a standardized, composite quality measure based on multiple postoperative endpoints representing the ideal "textbook" hospitalization. METHODS: Adult patients who underwent LTx at our institution between 2016 and 2019 were included. TO was defined as freedom from intraoperative complication, postoperative reintervention, 30-day intensive care unit or hospital readmission, length of stay >75th percentile of LTx patients, 90 day mortality, 30-day acute rejection, grade 3 primary graft dysfunction at 48 or 72 hours, postoperative extracorporeal membrane oxygenation, tracheostomy within 7 days, inpatient dialysis, reintubation, and extubation >48 hours post-transplant. Recipient, operative, financial characteristics, and post-transplant outcomes were recorded from institutional data and compared between TO and non-TO groups. RESULTS: Of 401 LTx recipients, 97 (24.2%) achieved TO. The most common reason for TO failure was extubation >48 hours post-transplant (N = 119, 39.1%); the least common was mortality (N = 15, 4.9%). Patient and graft survival were improved among patients who achieved versus failed TO (patient survival: log-rank P < 0.01; graft survival: log-rank P < 0.01). Rejection-free and chronic lung allograft dysfunction-free survival were similar between TO and non-TO groups (rejection-free survival: log-rank P = 0.07; chronic lung allograft dysfunction-free survival: log-rank P = 0.3). On average, patients who achieved TO incurred approximately $638,000 less in total inpatient charges compared to those who failed TO. CONCLUSIONS: TO in LTx was associated with favorable post-transplant outcomes and significant cost-savings. TO may offer providers and patients new insight into transplant center quality of care and highlight areas for improvement.

Same-teams versus different-teams for long distance lung procurement: A cost analysis.

OBJECTIVE: In an era of broader lung sharing, different-team transplantation (DT, procuring team from nonrecipient center) may streamline procurement logistics; however, safety and cost implications of DT remain unclear. To understand whether DT represents a safe means to reduce lung transplant (LTx) costs, we compared posttransplant outcomes and lung procurement and index hospitalization costs among matched DT and same-team transplantation (ST, procuring team from recipient center) cohorts at a single, high-volume institution. We hypothesized that DT reduces costs without compromising outcomes after LTx. METHODS: Patients who underwent DT between January 2016 to May 2020 were included. A cohort of patients who underwent ST was matched 1:3 (nearest neighbor) based on recipient age, disease group, lung allocation score, history of previous LTx, and bilateral versus single LTx. Posttransplant outcomes and costs were compared between groups. RESULTS: In total, 23 DT and 69 matched ST recipients were included. Perioperative outcomes and posttransplant survival were similar between groups. Compared with ST, DT was associated with similar lung procurement and index hospitalization costs (DT vs ST, procurement: median $65,991 vs $58,847, P = .16; index hospitalization: median $294,346 vs $322,189, P = .7). On average, procurement costs increased $3263 less per 100 nautical miles for DT versus ST; DT offered cost-savings when travel distances exceeded approximately 363 nautical miles. CONCLUSIONS: At our institution, DT and ST were associated with similar post-LTx outcomes; DT offered cost-savings with increasing procurement travel distance. These findings suggest that DT may mitigate logistical and financial burdens of lung procurement; however, further investigation in a multi-institutional cohort is warranted.

AAV9-mediated gene delivery to liver grafts during static cold storage in a rat liver transplant model.

Introduction: Recombinant adeno-associated virus (rAAV) is a novel strategy used clinically for gene delivery, but has not been characterized in the context of organ transplantation. We sought to determine the efficacy of rAAV-mediated gene delivery during static cold storage (SCS) prior to liver transplantation. Methods: A triple-plasmid transfection protocol was used to produce rAAV subtype-9 vectors containing firefly luciferase genomes in HEK293 cells. Lewis rat liver grafts were flushed and stored in cold HTK solution. Three experimental groups received rAAV at different doses, administered via the portal vein as a bolus during SCS. A control group did not receive rAAV (N = 2). Recipients then underwent syngeneic liver transplantation. Bioluminescence imaging to quantify in vivo luciferase expression was performed on post-operative days 7, 14, 28, and 56. Results: Control animals demonstrated no bioluminescent activity, while animals receiving rAAV-treated livers had increasing bioluminescence, peaking at four weeks but sustained to the eight-week endpoint. This result was confirmed by experimental endpoint tissue luciferase activity assay. Discussion: rAAV mediates gene transduction in liver grafts when administered during SCS and has potential for gene therapy applications in solid organ transplantation.

Adeno-associated virus mediates gene transduction after static cold storage treatment in rodent lung transplantation.

OBJECTIVE: Adeno-associated virus is a clinically used gene therapy vector but has not been studied in lung transplantation. We sought to determine the efficacy of adeno-associated virus delivery during static cold storage via the airway versus the pulmonary artery before lung transplantation in a rodent model. METHODS: Lewis rat lung grafts were treated with a dose of 8e8 or 4e9 viral genome/µL recombinant adeno-associated virus subtype-9 vectors containing firefly luciferase genomes administered via the pulmonary artery or airway during cold storage. A control group did not receive adeno-associated virus. Recipient syngeneic rats then underwent single left lung transplantation. Animals underwent bioluminescence imaging on postoperative days 7, 14, 28, and 56. Explanted tissues were prepared as lysates to quantify luciferase activity. Immunohistochemistry was performed to evaluate cellular transgene expression patterns. RESULTS: Control animals with no luminescent signal produced a background radiance of 6.1e4 p/s/cm2/sr. In the airway delivery group, mean radiance was greater than the control at 4e9 viral genome/µL postoperative day 7 radiance 6.9e4 p/s/cm2/sr (P = .04). In the pulmonary artery delivery group, we observed greater in vivo luminescence in animals receiving 4e9 viral genome/µL compared with all other groups. However, analysis of tissue lysate revealed greater luminescence in the airway delivery group and suggested off-target expression in heart and liver tissue in the pulmonary artery delivery group. Immunohistochemistry demonstrated transgene staining in distal airway epithelium and alveoli but sparing of the vasculature in the airway delivery group. CONCLUSIONS: Adeno-associated virus mediates gene transduction during static cold storage in rat lung isografts when administered via the airway and pulmonary artery. Airway administration leads to robust transgene expression in respiratory epithelial cells, whereas pulmonary artery administration targets alternative cell types and increases extrapulmonary transgene expression.

Textbook outcome in lung transplantation: Planned venoarterial extracorporeal membrane oxygenation versus off-pump support for patients without pulmonary hypertension.

BACKGROUND: Planned venoarterial extracorporeal membrane oxygenation (VA ECMO) is increasingly used during bilateral orthotopic lung transplantation (BOLT) and may be superior to off-pump support for patients without pulmonary hypertension. In this single-institution study, we compared rates of textbook outcome between BOLTs performed with planned VA ECMO or off-pump support for recipients with no or mild pulmonary hypertension. METHODS: Patients with no or mild pulmonary hypertension who underwent isolated BOLT between 1/2017 and 2/2021 with planned off-pump or VA ECMO support were included. Textbook outcome was defined as freedom from intraoperative complication, 30-day reintervention, 30-day readmission, post-transplant length of stay >30 days, 90-day mortality, 30-day acute rejection, grade 3 primary graft dysfunction at 48 or 72 hours, post-transplant ECMO, tracheostomy within 7 days, inpatient dialysis, reintubation, and extubation >48 hours post-transplant. Textbook outcome achievement was compared between groups using multivariable logistic regression. RESULTS: Two hundred thirty-seven BOLTs were included: 68 planned VA ECMO and 169 planned off-pump. 14 (20.6%) planned VA ECMO and 27 (16.0%) planned off-pump patients achieved textbook outcome. After adjustment for prior BOLT, lung allocation score, ischemic time, and intraoperative transfusions, planned VA ECMO was associated with higher odds of textbook outcome than planned off-pump support (odds ratio 3.89, 95% confidence interval 1.58-9.90, p = 0.004). CONCLUSIONS: At our institution, planned VA ECMO for isolated BOLT was associated with higher odds of textbook outcome than planned off-pump support among patients without pulmonary hypertension. Further investigation in a multi-institutional cohort is warranted to better elucidate the utility of this strategy.

Two Compartment Evaluation of Liver Grafts During Acellular Room Temperature Machine Perfusion (acRTMP) in a Rat Liver Transplant Model.

Background: Subnormothermic machine perfusion (SNMP) of liver grafts is currently less clinically developed than normothermic and hypothermic approaches, but may have logistical advantages. At intermediate temperatures, the oxygen demand of the graft is low enough to be satisfied with an acellular perfusate, obviating the need for oxygen carrying molecules. This intermediate metabolic rate, however, is sufficient to support the production of bile, which is emerging as an important indicator of graft injury and viability. In this study, we hypothesized that the biliary compartment would be more sensitive than perfusate in detecting graft injury during SNMP. Methods: To test this hypothesis in a rat model, we performed liver transplants with DCD and control liver grafts after 1 h of acellular room temperature machine perfusion (acRTMP) or static cold storage (SCS). Point of care liver function tests were measured in biliary and perfusate samples after 1 h of machine perfusion. Following transplantation, rats were sacrificed at 24 h for assessment of post-transplant graft function and histology. Results: All point-of-care liver function tests were significantly more concentrated in the biliary compartment than the perfusate compartment during acRTMP. DCD liver grafts could be distinguished from control liver grafts by significantly higher markers of hepatocyte injury (AST, ALT) in the biliary compartment, but not in the perfusate compartment. Classical markers of cholangiocyte injury, such as gammy-glut amyl transferase (GGT), amylase (AML), and alkaline phosphatase were detectable in the biliary compartment, but not in the perfusate compartment. In comparison to SCS, graft preservation by acRTMP produced a significant survival benefit in DCD liver transplantation (75 vs. 0%, p < 0.0030). Conclusion: Together, these findings demonstrate that during acRTMP, the biliary compartment may be a more sensitive indicator of graft injury than the perfusate compartment. Moreover, acRTMP provides superior graft preservation to SCS in rat DCD liver transplantation.

Stent Graft-induced Aortic Wall Injury: Incidence, Risk Factors, and Outcomes.

BACKGROUND: Stent graft-induced new entry has been described in thoracic endovascular aortic repair for aortic dissection. The incidence of stent graft-induced aortic wall injury (SAWI) related to iatrogenic injury in nondissections is incompletely described. We describe incidence, risk factors, and outcomes of SAWI. METHODS: All post-thoracic endovascular aortic repair computed tomography angiograms (January 2005 to December 2018) were reviewed for radiographic evidence of SAWI. Endograft-induced aortic dissections were likewise considered SAWI. Patient characteristics, time to SAWI, and need for reintervention were noted. Cox proportional hazards modeling was used to identify risk factors for SAWI. RESULTS: Within the study cohort (n = 430), 38 patients (9%) had SAWI during a median follow-up of 2.3 years (interquartile range, 4.8); 42% (n = 16) were proximal, 53% (n = 20) distal, and 5% (n = 2) both proximal and distal. Nine (23%) were distal intimal flap injuries in dissection cases, thus subclassifying them as stent graft-induced new entry. Twenty-nine percent of SAWI (n = 11) required reintervention. Of these, 45% (n = 5) were open, and 55% (n = 6) were endovascular. Thoracic endovascular aortic repair for acute dissection had a higher incidence of SAWI development (hazard ratio 4.6; 95% confidence interval, 2.4 to 9; P < .001) as compared with other indications. Use of devices with proximal bare springs or barbs was also associated with increased SAWI incidence (hazard ratio 5.3; 95% confidence interval, 2.6 to 11.0; P < .001). CONCLUSIONS: The rate of SAWI after thoracic endovascular aortic repair is low (9%), but nearly one third will require reintervention. Thoracic endovascular aortic repair in the setting of acute dissection and use of devices with proximal bare springs or barbs were associated with an increased incidence of SAWI.

Textbook surgical outcome in lung transplantation: Analysis of a US national registry.

INTRO: Textbook surgical outcome (TO) is a novel composite quality measure in lung transplantation (LTx). Compared to 1-year survival metrics, TO may better differentiate center performance, and motivate improvements in care. To understand the feasibility of implementing this metric, we defined TO in LTx using US national data, and evaluated its ability to predict post-transplant outcomes and differentiate center performance. METHODS: Adult patients who underwent isolated LTx between 2016 and 2019 were included. TO was defined as freedom from post-transplant length of stay > 30 days, 90-day mortality, intubation or extracorporeal membrane oxygenation at 72 h post-transplant, post-transplant ventilator support lasting ≥5 days, postoperative airway dehiscence, inpatient dialysis, pre-discharge acute rejection, and grade 3 primary graft dysfunction at 72 h. Recipient and donor characteristics and post-transplant outcomes were compared between patients who achieved and failed TO. RESULTS: Of 8959 lung transplant recipients, 4664 (52.1%) achieved TO. Patient and graft survival were improved among patients who achieved TO (both log-rank P < .0001). Among 62 centers, adjusted rates of TO ranged from 27.0% to 72.4% reflecting a wide variability in center-level performance. CONCLUSION: TO defined using national data may represent a novel composite metric to guide quality improvement in LTx across US transplant centers. SUMMARY: In this study we defined textbook outcome (TO) for lung transplantation (LTx) using US national data. We found that achievement of TO was associated with improved post-transplant survival, and wide variability in center-level LTx performance. These findings suggest that TO could be readily implemented to compare quality of care among US LTx centers.

Lung Transplantation After Ex Vivo Lung Perfusion Early Outcomes From a US National Registry.

OBJECTIVE: The objective of this study was to examine early lung transplant outcomes following EVLP using a large national transplant registry. SUMMARY OF BACKGROUND DATA: Lung transplantation in the United States continues to be constrained by a limited supply of donor organs. EVLP has the potential to significantly increase the available pool of donor lung allografts through the reconditioning of "marginal" organs. METHODS: The united network for organ sharing registry was queried for all adults (age ≥18) who underwent first-time lung transplantation between March 2018 (when united network for organ sharing began collecting confirmed donor EVLP status) and June 2019. Transplants were stratified by EVLP use. The primary outcome was short-term survival and secondary outcomes included acute rejection before discharge and need for extracorpo-real membrane oxygenation support post-transplant. RESULTS: A total of 3334 recipients met inclusion criteria including 155 (5%) and 3179 (95%) who did and did not receive allografts that had undergone EVLP, respectively. On unadjusted descriptive analysis, EVLP and non-EVLP cohorts had similar 180-day survival (92% vs 92%, P = 0.9). EVLP use was associated with a similar rate of acute rejection (13% vs 9%, P = 0.08) but increased rate of early extracorporeal membrane oxygenation use (12% vs 7%, P = 0.04). After adjustment, EVLP use was not associated with significantly increased mortality (adjusted hazard ratio 0.99, 95% confidence interval 0.62-1.58) or acute rejection (adjusted odds ratio 0.89, 95% confidence interval 0.40-1.97) compared to non-EVLP use. CONCLUSIONS: In the largest national series of EVLP lung transplant recipients, EVLP is associated with early recipient outcomes comparable to that of non-EVLP recipients with similar baseline characteristics. Longer term follow-up data is needed to further assess the impact of EVLP on post-lung transplant outcomes.

Lung transplantation after ex vivo lung perfusion versus static cold storage: An institutional cost analysis.

Ex vivo lung perfusion (EVLP) is a novel lung preservation strategy that facilitates the use of marginal allografts; however, it is more expensive than static cold storage (SCS). To understand how preservation method might affect postoperative costs, we compared outcomes and index hospitalization costs among matched EVLP and SCS preserved lung transplant (LTx) recipients at a single, high-volume institution. A total of 22 EVLP and 66 matched SCS LTx recipients were included; SCS grafts were further stratified as either standard-criteria (SCD) or extended-criteria donors (ECD). Median total preservation time was 857, 409, and 438 min for EVLP, SCD, and ECD lungs, respectively (p < .0001). EVLP patients had similar perioperative outcomes and posttransplant survival compared to SCS SCD and ECD recipients. Excluding device-specific costs, total direct variable costs were similar among EVLP, SCD, and ECD recipients (median $200,404, vs. $154,709 vs. $168,334, p =  .11). The median direct contribution margin was positive for EVLP recipients, and similar to that for SCD and ECD graft recipients (all p > .99). These findings demonstrate that the use of EVLP was profitable at an institutional level; however, further investigation is needed to better understand the financial implications of EVLP in facilitating donor pool expansion in an era of broader lung sharing.

Incidence and Diagnostic Challenges of Bowel Ischemia after Continuous-flow Left Ventricular Assist Device Therapy.

Long-term continuous-flow left ventricular assist device (CFLVAD) therapy is limited by complications. Compared with stroke and renal dysfunction, post-CFLVAD bowel ischemia is poorly characterized. Adult patients who underwent first-time durable CFLVAD implantation at our institution between 2008 and 2018 were identified and screened for bowel ischemia using Current Procedural Terminology codes for abdominal surgical exploration and International Classification of Disease codes for intestinal vascular insufficiency. Patients who developed biopsy-proven bowel ischemia (cases) were matched to controls (1:1, nearest neighbor, caliper = 0.29) based on preoperative characteristics. Incidences of postoperative right heart failure and renal replacement therapy were compared using McNemar's test. One year survival was estimated using the Kaplan-Meier method. Overall, 711 patients underwent CFLVAD implantation. Nineteen (2.7%) developed bowel ischemia (cases) median 17 days postimplantation (IQR 8-71). The majority of cases were male (78.9%), Black (63.2%), received HeartMate II (57.9%), treated as destination therapy (78.9%), and had a history of hypertension (89.5%), chronic kidney disease (84.2%), hyperlipidemia (84.2%), smoking (78.9%), and atrial fibrillation (57.9%). Post-LVAD, case patients were more likely to develop moderate-severe right heart failure (89.5% vs. 68.4%, p = 0.005), require renal replacement therapy (21.1% vs. 0%, p < 0.001), and less likely to survive to discharge (52.6% vs. 89.5%, p = 0.02) compared with controls. Case subjects demonstrated worse 1 year survival. While less common than stroke and renal dysfunction, post-CFLVAD bowel ischemia is associated with high 1 year mortality. Multi-institutional registries should consider reporting abdominal complications such as bowel ischemia as an adverse event to further investigate these trends and identify predictors of this complication to reduce patient mortality.

A pragmatic outreach pilot to understand and overcome barriers to COVID-19 vaccination in abdominal organ transplant.

BACKGROUND: Solid organ transplant recipients (SOTRs) are at increased risk for adverse outcomes with coronavirus disease 19 (COVID-19). Early data show a lower severe acute respiratory syndrome virus 2 (SARS-CoV-2) spike antibody immune response among SOTRs leading to patient concerns about vaccine efficacy. Public health messaging has largely left out immunocompromized individuals leading to a higher risk of vaccine misinformation. The American Society of Transplantation recommends COVID-19 vaccination for all SOTRs; however, patient concerns and beliefs about vaccination are largely unknown. METHODS: We conducted a transplant-center-based, pragmatic pilot trial to encourage COVID-19 vaccination among 103 unvaccinated SOTRs. We assessed vaccine concerns, barriers to vaccination, answered questions about efficacy, side effects, and clinical recommendations. RESULTS: A total of 24% (n = 25) of SOTRs reported that they will schedule COVID-19 vaccination after the study call, 46% reported that they will consider vaccination in the future, and 30% said they will not consider vaccination. Older age and White race were associated with lower willingness to schedule the vaccine, whereas Black race and longer time from transplant were associated with higher willingness. Common vaccine concerns included lack of long-term data, inconsistent messaging from providers, scheduling inconvenience, and insufficient resources. Follow-up approximately 1 month after the initial outreach found 52% (n = 13) of liver transplant recipients, and 10% (n = 3) of kidney transplant recipients subsequently received COVID-19 vaccines for a vaccination rate of 29% among respondents. CONCLUSION: Transplant center-based vaccine outreach efforts can decrease misinformation and increase vaccination uptake; however, vaccine-related mistrust remains high.

Point-of-Care Assessment of DCD Livers During Normothermic Machine Perfusion in a Nonhuman Primate Model.

Normothermic machine perfusion (NMP) provides clinicians an opportunity to assess marginal livers before transplantation. However, objective criteria and point-of-care (POC) biomarkers to predict risk and guide decision making are lacking. In this investigation, we characterized trends in POC biomarkers during NMP and compared primate donation after circulatory death (DCD) livers with short and prolonged warm ischemic injury. Following asystole, livers were subjected to either 5 minutes (DCD-5min, n = 4) or 45 minutes (DCD-45min, n = 4) of warm ischemia time. Livers were flushed with heparinized UW solution, and preserved in cold storage before NMP. During flow-controlled NMP, circulating perfusate and tissue biopsies were collected at 0, 2, 4, 6, and 8 hours for analysis. DCD-45min livers had greater terminal portal vein pressure (8.5 vs. 13.3 mm Hg, P = 0.027) and terminal portal vein resistance (16.3 vs. 32.4 Wood units, P = 0.005). During perfusion, DCD-45min livers had equivalent terminal lactate clearance (93% vs. 96%, P = 0.344), greater terminal alanine aminotransferase (163 vs. 883 U/L, P = 0.002), and greater terminal perfusate gamma glutamyltransferase (GGT) (5.0 vs. 31.7 U/L, P = 0.002). DCD-45min livers had higher circulating levels of flavin mononucleotide (FMN) at hours 2 and 4 of perfusion (136 vs. 250 ng/mL, P = 0.029; and 158 vs. 293 ng/mL, P = 0.003; respectively). DCD-5min livers produced more bile and demonstrated progressive decline in bile lactate dehydrogenase, whereas DCD-45min livers did not. On blinded histologic evaluation, DCD-45min livers demonstrated greater injury and necrosis at late stages of perfusion, indicative of nonviability. Conclusion: Objective criteria are needed to define graft viability during NMP. Perfusate lactate clearance does not discriminate between viable and nonviable livers during NMP. Perfusate GGT and FMN may represent POC biomarkers predictive of liver injury during NMP.