Multinational Analysis of Marginal Liver Grafts Based on the Eurotransplant Extended Donor Criteria.

OBJECTIVE: To evaluate the outcome of marginal liver grafts based on the Eurotransplant extended donor criteria (ECD) criteria. SUMMARY BACKGROUND DATA: Eurotransplant uses a broad definition of ECD criteria (age >65 years, steatosis >40%, BMI >30 kg/m2, ICU stay >7 days, DCD, and certain laboratory parameters) for allocating organs to recipients who have consented to marginal grafts. Historically, marginal liver grafts were associated with increased rates of dysfunction. METHODS: Retrospective cohort analysis using the German Transplant Registry (GTR) and the US Scientific Registry of Transplant Recipients (SRTR) from 2006-2016. Results were validated with recent SRTR data (2017-2022). Donors were classified according to the Eurotransplant ECD criteria, DCD was excluded. Data were analyzed with cut-off prediction, binomial logistic regression, and multivariate Cox regression. RESULTS: The study analyzed 92,330 deceased brain-dead donors (87% SRTR) and 70,374 transplants (87% SRTR) in adult recipients. Predominant ECD factors were donor age in Germany (30%) and BMI in the US (28%). Except for donor age, grafts meeting ECD criteria were not associated with impaired 1- or 3-year survival. Cut-offs had little to no predictive value for 30-day graft survival (AUROC 0.49 - 0.52) and were nominally higher for age (72 vs. 65 years) in Germany as compared to those defined by current Eurotransplant criteria. CONCLUSIONS: The outcome of transplanted grafts from higher risk donors was nearly equal to standard donors with Eurotransplant criteria failing to predict survival of marginal grafts. Modifying ECD criteria could improve graft allocation and potentially expand the donor pool.

Hepatocellular Carcinoma Surveillance Patterns and Outcomes in Patients With Cirrhosis.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) surveillance is associated with improved early detection and reduced mortality, although practice patterns and effectiveness vary in clinical practice. We aimed to characterize HCC surveillance patterns in a large, diverse cohort of patients with HCC. METHODS: We conducted a retrospective cohort study of patients diagnosed with HCC between January 2008 and December 2022 at 2 large US health systems. We recorded imaging receipt in the year before HCC diagnosis: ultrasound plus α-fetoprotein (AFP), ultrasound alone, multiphasic contrast-enhanced computed tomography (CT)/magnetic resonance imaging (MRI), and no liver imaging. We used multivariable logistic and Cox regression analysis to compare early tumor detection, curative treatment receipt, and overall survival between surveillance strategies. RESULTS: Among 2028 patients with HCC (46.7% Barcelona Clinic Liver Cancer stage A), 703 (34.7%) had ultrasound plus AFP, 293 (14.5%) had ultrasound alone, 326 (16.1%) had multiphasic CT/MRI, and 706 (34.8%) had no imaging in the year before HCC diagnosis. Over the study period, proportions without imaging were stable, whereas use of CT/MRI increased. Compared with no imaging, CT/MRI and ultrasound plus AFP, but not ultrasound alone, were associated with early stage HCC detection and curative treatment. Compared with ultrasound alone, CT/MRI and ultrasound plus AFP were associated with increased early stage detection. CONCLUSIONS: HCC surveillance patterns vary in clinical practice and are associated with differing clinical outcomes. While awaiting data to determine if CT or MRI surveillance can be performed in a cost-effective manner in selected patients, AFP has a complementary role to ultrasound-based surveillance, supporting its adoption in practice guidelines.

Increasing practice and acceptable outcomes of high-MELD living donor liver transplantation in the USA.

Recent deceased-donor allocation changes in the United States may have increased high-Model for End-Stage Liver Disease (MELD) living donor liver transplantation (LDLT); however, outcomes in these patients remain poorly defined. We aimed to examine the impact of the MELD score on LDLT outcomes. Using UNOS data (January 1, 2010-December 31, 2021), LDLT recipients were identified and stratified into low-MELD (<15), intermediate-MELD (15-24), and high-MELD (≥25) groups. We compared outcomes between MELD-stratified LDLT groups and between MELD-stratified LDLT and donation after brain death liver transplantation recipients. We used Kaplan-Meier analysis to compare graft survival rates and multivariable Cox proportional hazards modeling to identify factors associated with graft outcomes. Of 3558 LDLTs, 1605 (45.1%) were low-MELD, 1616 (45.4%) intermediate-MELD, and 337 (9.5%) high-MELD. Over the study period, the annual number of LDLTs increased from 282 to 569, and the proportion of high-MELD LDLTs increased from 3.9% to 7.7%. Graft survival was significantly higher in low-MELD versus high-MELD LDLT recipients (adjusted HR = 1.36, 95% CI: 1.03-1.79); however, 5-year survival exceeded 70.0% in both groups. We observed no significant difference in graft survival between high-MELD LDLT and high-MELD donation after brain death liver transplantation recipients (adjusted HR: 1.25, 95% CI:0.99-1.58), with a 5-year survival of 71.5% and 77.3%, respectively. Low LDLT center volume (<3 LDLTs/year) and recipient life support requirement were both associated with inferior graft outcomes among high-MELD LDLT recipients. While higher MELD scores confer graft failure risk in LDLT, high-MELD LDLT outcomes are acceptable with similar outcomes to MELD-stratified donation after brain death liver transplantation recipients. Future practice guidance should consider the expansion of LDLT recommendations to high-MELD recipients in centers with expertise to help reduce donor shortage.

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

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

Association between bridging therapy and posttransplant outcomes in patients with HCC within Milan criteria: A systematic review and meta-analysis.

Liver transplantation is the curative therapy of choice for patients with early-stage HCC. Locoregional therapies are often employed as a bridge to reduce the risk of waitlist dropout; however, their association with posttransplant outcomes is unclear. We conducted a systematic review using Ovid MEDLINE and EMBASE to identify studies published between database inception and August 2, 2023, which reported posttransplant recurrence-free survival and overall survival among patients transplanted for HCC within Milan criteria, stratified by receipt of bridging therapy. Pooled HRs were calculated for each outcome using the DerSimonian and Laird method for a random-effects model. We identified 38 studies, including 19,671 patients who received and 20,148 patients who did not receive bridging therapy. Bridging therapy was not associated with significant differences in recurrence-free survival (pooled HR: 0.91, 95% CI: 0.77-1.08; I2 =39%) or overall survival (pooled HR: 1.09, 95% CI: 0.95-1.24; I2 =47%). Results were relatively consistent across subgroups, including geographic location and study period. Studies were discordant regarding the differential strength of association by pretreatment tumor burden and pathologic response, but potential benefits of locoregional therapy were mitigated in those who received 3 or more treatments. Adverse events were reported in a minority of studies, but when reported occurred in 6%-15% of the patients. Few studies reported loss to follow-up and most had a risk of residual confounding. Bridging therapy is not associated with improvements in posttransplant recurrence-free or overall survival among patients with HCC within Milan criteria. The risk-benefit ratio of bridging therapy likely differs based on the risk of waitlist dropout.

The financial burden after liver transplantation is significant among commercially insured adults: A large US National Cohort.

Liver transplantation (LT) is lifesaving for patients with cirrhosis; however, the resultant financial burden to patients has not been well characterized. We aimed to provide a nationally representative portrayal of patient financial burden after LT. Adult recipients of LT from 2006 to 2021 were identified using IQVIA PharMetrics® Plus for Academics-a large nationally representative claims database of commercially insured Americans. Patient financial liability (ie, what patients owe) was estimated using the difference between allowed and paid costs for adjudicated medical/pharmacy claims. Descriptive statistics were provided stratified by the financial liability group within 1 year after LT. Multivariable logistic regression modeling identified factors associated with high/extreme liability adjusting for covariates. Potential indirect costs of post-LT care were estimated based on hourly wages lost for care. Among 1412 recipients of LT, financial liability was heterogeneous-~3% had no liability and 21% had extreme liability > $10K for 1-year post-LT care; most (69%) paid between $1 and 10K, with 48% having liability >$5K. Factors associated with >$5K liability included older age, insurance/enrollment type, US region, history of HCC, and simultaneous liver-kidney transplant (for liability >$10K). Medication costs comprised ~30% of outpatient financial liability. Potential indirect costs from wages lost were $2,201-$6,073 per person, depending on an hourly wage. In a large national cohort of commercially insured recipients of LT, financial liability was highly variable across sociodemographic and clinical characteristics; nearly 1 out of 2 recipients of LT owed >$5K for 1 year of post-LT care. Transplant programs should help patients anticipate potential costs and identify vulnerable populations who would benefit from enhanced financial counseling.

The effect of an organ procurement organization surgeon on pediatric organ utilization.

INTRODUCTION: Organ procurement organizations (OPO) have started to employ transplant-trained surgeons dedicated to organ procurement with the aim to increase allograft utilization and enhance the use of procured organs. We investigated the effects of an OPO-employed surgeon on the procurement and utilization of organs from pediatric donors within the Southwestern Transplant Alliance OPO. METHODS: OPO data were obtained for all procurements that were performed between 2014 and 2019. The analysis was performed to see if the presence of an OPO donor surgeon impacted the utilization of pediatric livers. Donor and recipient demographic data were examined between allografts procured with the presence of an OPO surgeon (OPO-Present) and those without an OPO surgeon (OPO-Absent). A p-value of <.05 was considered significant. RESULTS: Of 149 pediatric procurements, 91 included an OPO-donor surgeon. In procurements with OPO-Present, donors were younger (8.2 vs. 11.2, p < .05) and had longer distances to travel to the recipient center (334 vs. 175 miles p < .05), but had comparable cold ischemic times. In terms of organ share type, more OPO-Present livers were shared nationally and there was no difference in discard rate between OPO-Present and OPO-Absent procurements. Finally, OPO-Present livers were more likely to be transplanted to pediatric recipients compared to OPO-Absent (47.3% vs. 24.1% p < .05). CONCLUSION: The presence of an OPO surgeon has impacted organ utilization, leading to increased transplantation of pediatric livers in pediatric recipients, and has expanded the geographical share of pediatric livers.

Early Graft Failure After Living-Donor Liver Transplant.

BACKGROUND: Living-donor liver transplantation (LDLT) has been increasing in the USA. While data exist on longer-term patient and graft outcomes, a contemporary analysis of short-term outcomes is needed. AIM: Evaluate short-term (30-day) graft failure rates and identify predictors associated with these outcomes. METHODS: Adult (≥ 18) LDLT recipients from 01/2004 to 12/2021 were analyzed from the United States Scientific Registry of Transplant Recipients. Graft status at 30 days was assessed with graft failure defined as retransplantation or death. Comparison of continuous and categorical variables was performed and a multivariable logistic regression was used to identify risk factors of early graft failure. RESULTS: During the study period, 4544 LDLTs were performed with a graft failure rate of 3.4% (155) at 30 days. Grafts from male donors (aOR: 0.63, CI 0.44-0.89), right lobe grafts (aOR: 0.40, CI 0.27-0.61), recipients aged > 60 years (aOR: 0.52, CI 0.32-0.86), and higher recipient albumin (aOR: 0.73, CI 0.57-0.93) were associated with superior early graft outcomes, whereas Asian recipient race (vs. White; aOR: 3.75, CI 1.98-7.10) and a history of recipient PVT (aOR: 2.7, CI 1.52-4.78) were associated with inferior outcomes. LDLTs performed during the most recent 2016-2021 period (compared to 2004-2009 and 2010-2015) resulted in significantly superior outcomes (aOR: 0.45, p < 0.001). CONCLUSION: Our study demonstrates that while short-term adult LDLT graft failure is uncommon, there are opportunities for optimizing outcomes by prioritizing right lobe donation, improving candidate nutritional status, and careful pre-transplant risk assessment of candidates with known PVT. Notably, a period effect exists whereby increased LDLT experience in the most recent era correlated with improved outcomes.

A contemporary analysis of 20,086 deceased donor liver biopsies.

BACKGROUND: Pre-transplant deceased donor liver biopsy may impact decision making; however, interpretation of the results remains variable and depends on accepting center practice patterns. METHODS: In this cohort study, adult recipients from 04/01/2015-12/31/2020 were identified using the UNOS STARfile data. The deceased donor liver biopsies were stratified by risk based on degree of fibrosis, macrovesicular fat content, and level of portal infiltration (low-risk: no fibrosis, no portal infiltrates, and <30% macrosteatosis; moderate-risk: some fibrosis or mild infiltrates and <30% macrosteatosis; high-risk: most fibrosis, moderate/marked infiltrates, or ≥30% macrosteatosis). Graft utilization, donor risk profile, and recipient outcomes were compared across groups. RESULTS: Of the 51,094 donor livers available, 20,086 (39.3%) were biopsied, and 34,606 (67.7%) were transplanted. Of the transplanted livers, 14,908 (43.1%) were biopsied. The transplanted grafts had lower mean macrovesicular fat content (9.3% transplanted vs. 26.9% non-transplanted, P < 0.001) and less often had any degree of fibrosis (20.9% vs. 39.9%, P < 0.001) or portal infiltration (51.3% vs. 58.2%, P < 0.001) versus non-transplanted grafts. Post-transplant recipient LOS (14.2 days high-risk vs. 15.2 days low-risk, P = 0.170) and 1-year graft survival (90.5% vs. 91.7%, P = 0.137) did not differ significantly between high- versus low-risk groups. Kaplan-Meier survival estimates further revealed no differences in the 5-year graft survival across risk strata (P = 0.833). Of the 5178 grafts biopsied and turned down, PSM revealed 1338 (26.0%) were potentially useable based on biopsy results and donor characteristics. CONCLUSION: Carefully matched deceased donor livers with some fibrosis, inflammation, or steatosis ≥30% may be suitable for transplantation. Further study of this group of grafts may decrease turndowns of potentially useable organs.

Machine learning-based mortality prediction models using national liver transplantation registries are feasible but have limited utility across countries.

Many countries curate national registries of liver transplant (LT) data. These registries are often used to generate predictive models; however, potential performance and transferability of these models remain unclear. We used data from 3 national registries and developed machine learning algorithm (MLA)-based models to predict 90-day post-LT mortality within and across countries. Predictive performance and external validity of each model were assessed. Prospectively collected data of adult patients (aged ≥18 years) who underwent primary LTs between January 2008 and December 2018 from the Canadian Organ Replacement Registry (Canada), National Health Service Blood and Transplantation (United Kingdom), and United Network for Organ Sharing (United States) were used to develop MLA models to predict 90-day post-LT mortality. Models were developed using each registry individually (based on variables inherent to the individual databases) and using all 3 registries combined (variables in common between the registries [harmonized]). The model performance was evaluated using area under the receiver operating characteristic (AUROC) curve. The number of patients included was as follows: Canada, n = 1214; the United Kingdom, n = 5287; and the United States, n = 59,558. The best performing MLA-based model was ridge regression across both individual registries and harmonized data sets. Model performance diminished from individualized to the harmonized registries, especially in Canada (individualized ridge: AUROC, 0.74; range, 0.73-0.74; harmonized: AUROC, 0.68; range, 0.50-0.73) and US (individualized ridge: AUROC, 0.71; range, 0.70-0.71; harmonized: AUROC, 0.66; range, 0.66-0.66) data sets. External model performance across countries was poor overall. MLA-based models yield a fair discriminatory potential when used within individual databases. However, the external validity of these models is poor when applied across countries. Standardization of registry-based variables could facilitate the added value of MLA-based models in informing decision making in future LTs.

Correlation of LI-RADS 3 or 4 Observations with Histopathologic Diagnosis in Patients with Cirrhosis.

Patients with cirrhosis are high risk for developing hepatocellular carcinoma (HCC) and warrant surveillance using abdominal ultrasound and α-fetoprotein.1 Those with positive surveillance results should undergo diagnostic evaluation with multiphase computed tomography (CT) or magnetic resonance imaging (MRI). The LI-RADS system is an evidence-based system to classify observations on CT or MRI in at-risk patients, ranging from LR-1 (definite benign) to LR-5 (definite HCC), with LR-3 and LR-4 observations being intermediate risk for HCC.2 LR-3 and LR-4 observations are observed on CT or MRI in more than one-fourth of patients undergoing HCC surveillance and have a high, yet variable, risk for progression to HCC.3 Approximately one-third of patients with LR-3 observations and more than two-thirds of LR-4 observations develop HCC, and surveillance strategies vary widely in practice.4,5 Variation in radiographic appearance and natural history of these observations suggests that this may be a heterogeneous group of patients; however, their histopathology has not been well described. Herein, we correlated imaging findings and explant histopathology from liver transplant recipients with at least 1 LR-3 or LR-4 observation on CT or MRI within 6 months preceding transplantation.

Dynamic risk profiling of HCC recurrence after curative intent liver resection.

BACKGROUND AND AIMS: Following liver resection (LR) for HCC, the likelihood of survival is dynamic, in that multiple recurrences and/or metastases are possible, each having variable impacts on outcomes. We sought to evaluate the natural progression, pattern, and timing of various disease states after LR for HCC using multistate modeling and to create a practical calculator to provide prognostic information for patients and clinicians. APPROACH AND RESULTS: Adult patients undergoing LR for HCC between January 2000 and December 2018 were retrospectively identified at a single center. Multistate analysis modeled post-LR tumor progression by describing transitions between distinct disease states. In this model, the states included surgery, intrahepatic recurrence (first, second, third, fourth, fifth), distant metastasis with or without intrahepatic recurrence, and death. Of the 486 patients included, 169 (34.8%) remained recurrence-free, 205 (42.2%) developed intrahepatic recurrence, 80 (16.5%) developed distant metastasis, and 32 (7%) died. For an average patient having undergone LR, there was a 33.1% chance of remaining disease-free, a 31.0% chance of at least one intrahepatic recurrence, a 16.3% chance of distant metastasis, and a 19.8% chance of death within the first 60 months post-LR. The transition probability from surgery to first intrahepatic recurrence, without a subsequent state transition, increased from 3% (3 months) to 17.4% (30 months) and 17.2% (60 months). Factors that could modify these probabilities included tumor size, satellite lesions, and microvascular invasion. The online multistate model calculator can be found on https://multistatehcc.shinyapps.io/home/. CONCLUSIONS: In contrast to standard single time-to-event estimates, multistate modeling provides more realistic prognostication of outcomes after LR for HCC by taking into account many postoperative disease states and transitions between them. Our multistate modeling calculator can provide meaningful data to guide the management of patients undergoing postoperative surveillance and therapy.

Biliary atresia and liver transplantation in the United States: A contemporary analysis.

BACKGROUND: Biliary atresia (BA) remains the number one indication for paediatric liver transplantation (LT) worldwide but is an uncommon indication for older LT recipients. The impact of recent donor allocation changes, pervasive organ shortage and evolving LT practices on the BA LT population is unknown. METHODS: We identified patients who underwent LT between January 2010 and December 2021 using the UNOS database. We compared clinical outcomes between patients with BA and those with non-BA cholestatic liver disease. Groups were stratified by age, <12 years (allocated via PELD system) and ≥12 years (allocated via MELD system). Waitlist outcomes were compared using competing-risk regression analysis, graft survival rates were compared using Kaplan-Meier time-to-event analysis and Cox proportional hazards modelling provided adjusted estimates. RESULTS: There were 2754 BA LT waitlist additions and 2206 BA LTs (1937 <12 years [younger], 269 ≥12 years [older]). There were no differences in waitlist mortality between BA and non-BA cholestatic patients. Among BA LT recipients, there were 441 (20.0%) living-donor liver transplantations (LDLT) and 611 (27.7%) split deceased-donor LTs. Five-year graft survival was significantly higher among BA versus non-BA cholestatic patients in the older group (88.3% vs. 79.5%, p < .01) but not younger group (89.3% vs. 89.5%). Among BA LT recipients, improved graft outcomes were associated with LDLT (vs. split LT: HR: 2, 95% CI: 1.03-3.91) and higher transplant volume (volume >100 vs. <40 BA LTs: HR: 3.41, 95% CI: 1.87-6.2). CONCLUSION: Liver transplant outcomes among BA patients are excellent, with LDLT and higher transplant centre volume associated with optimal graft outcomes.

Outcomes after liver transplantation using deceased after circulatory death donors: A comparison of outcomes in the UK and the US.

BACKGROUND AND AIMS: Identifying international differences in utilization and outcomes of liver transplantation (LT) after donation after circulatory death (DCD) donation provides a unique opportunity for benchmarking and population-level insight. METHODS: Adult (≥18 years) LT data between 2008 and 2018 from the UK and US were used to assess mortality and graft failure after DCD LT. We used time-dependent Cox-regression methods to estimate hazard ratios (HR) for risk-adjusted short-term (0-90 days) and longer-term (90 days-5 years) outcomes. RESULTS: One-thousand five-hundred-and-sixty LT receipts from the UK and 3426 from the US were included. Over the study period, the use of DCD livers increased from 15.7% to 23.9% in the UK compared to 5.1% to 7.6% in the US. In the UK, DCD donors were older (UK:51 vs. US:33 years) with longer cold ischaemia time (UK: 437 vs. US: 333 min). Recipients in the US had higher Model for End-stage Liver Disease (MELD) scores, higher body mass index, higher proportions of ascites, encephalopathy, diabetes and previous abdominal surgeries. No difference in the risk-adjusted short-term mortality or graft failure was observed between the countries. In the longer-term (90 days-5 years), the UK had lower mortality and graft failure (adj.mortality HR:UK: 0.63 (95% CI: 0.49-0.80); graft failure HR: UK: 0.72, 95% CI: 0.58-0.91). The cumulative incidence of retransplantation was higher in the UK (5 years: UK: 11.9% vs. 4.6%; p < .001). CONCLUSIONS: For those receiving a DCD LT, longer-term post-transplant outcomes in the UK are superior to the US, however, significant differences in recipient illness, graft quality and access to retransplantation were seen between the two countries.

Delayed graft function in pediatric living donor kidney transplantation.

BACKGROUND: Pediatric recipients of living donor kidneys have a low rate of delayed graft function (DGF). We examined the incidence, risk factors and outcomes of DGF in pediatric patients who received a living donor allograft. METHODS: The STARfile was queried to examine all pediatric patients transplanted with a living donor kidney between 2000 and 2020. Donor and recipient demographic data were examined, as were survival and outcomes. Recipients were stratified into DGF and no DGF groups. DGF was defined as the need for dialysis within the first week after transplant. RESULTS: 6480 pediatric patients received a living donor (LD) kidney transplant during the study period. 269 (4.2%) developed DGF post-transplant. Donors were similar in age, creatinine, and cold ischemia time. Recipients of kidneys with DGF were similar in age, sensitization status and HLA mismatch. Focal segmental glomerulosclerosis (FSGS) was the most common diagnosis in recipients with DGF, and allograft thrombosis was the most common cause of graft loss in this group. Small recipients (weight < 15 kg) were found to have a significantly higher rate of DGF. Length of stay doubled in recipients with DGF, and rejection rates were higher post-transplant. Recipients of LD kidneys who developed DGF had significantly worse 1 year allograft survival (67% vs. 98%, p < .0001). CONCLUSIONS: Pediatric living donor kidney transplant recipients who experience DGF have significantly poorer allograft survival. Optimizing the donor and recipient matching to avoid compounding risks may allow for better outcomes.

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.

Low utilization of adult-to-adult LDLT in Western countries despite excellent outcomes: International multicenter analysis of the US, the UK, and Canada.

BACKGROUND & AIMS: Adult-to-adult living donor liver transplantation (LDLT) offers an opportunity to decrease the liver transplant waitlist and reduce waitlist mortality. We sought to compare donor and recipient characteristics and post-transplant outcomes after LDLT in the US, the UK, and Canada. METHODS: This is a retrospective multicenter cohort-study of adults (≥18-years) who underwent primary LDLT between Jan-2008 and Dec-2018 from three national liver transplantation registries: United Network for Organ Sharing (US), National Health Service Blood and Transplantation (UK), and the Canadian Organ Replacement Registry (Canada). Patients undergoing retransplantation or multi-organ transplantation were excluded. Post-transplant survival was evaluated using the Kaplan-Meier method, and multivariable adjustments were performed using Cox proportional-hazards models with mixed-effect modeling. RESULTS: A total of 2,954 living donor liver transplants were performed (US: n = 2,328; Canada: n = 529; UK: n = 97). Canada has maintained the highest proportion of LDLT utilization over time (proportion of LDLT in 2008 - US: 3.3%; Canada: 19.5%; UK: 1.7%; p <0.001 - in 2018 - US: 5.0%; Canada: 13.6%; UK: 0.4%; p <0.001). The 1-, 5-, and 10-year patient survival was 92.6%, 82.8%, and 70.0% in the US vs. 96.1%, 89.9%, and 82.2% in Canada vs. 91.4%, 85.4%, and 66.7% in the UK. After adjustment for characteristics of donors, recipients, transplant year, and treating transplant center as a random effect, all countries had a non-statistically significantly different mortality hazard post-LDLT (Ref US: Canada hazard ratio 0.53, 95% CI 0.28-1.01, p = 0.05; UK hazard ratio 1.09, 95% CI 0.59-2.02, p = 0.78). CONCLUSIONS: The use of LDLT has remained low in the US, the UK and Canada. Despite this, long-term survival is excellent. Continued efforts to increase LDLT utilization in these countries may be warranted due to the growing waitlist and differences in allocation that may disadvantage patients currently awaiting liver transplantation. LAY SUMMARY: This multicenter international comparative analysis of living donor liver transplantation in the United States, the United Kingdom, and Canada demonstrates that despite low use of the procedure, the long-term outcomes are excellent. In addition, the mortality risk is not statistically significantly different between the evaluated countries. However, the incidence and risk of retransplantation differs between the countries, being the highest in the United Kingdom and lowest in the United States.

The Toronto Postliver Transplantation Hepatocellular Carcinoma Recurrence Calculator: A Machine Learning Approach.

Liver transplantation (LT) listing criteria for hepatocellular carcinoma (HCC) remain controversial. To optimize the utility of limited donor organs, this study aims to leverage machine learning to develop an accurate posttransplantation HCC recurrence prediction calculator. Patients with HCC listed for LT from 2000 to 2016 were identified, with 739 patients who underwent LT used for modeling. Data included serial imaging, alpha-fetoprotein (AFP), locoregional therapies, treatment response, and posttransplantation outcomes. We compared the CoxNet (regularized Cox regression), survival random forest, survival support vector machine, and DeepSurv machine learning algorithms via the mean cross-validated concordance index. We validated the selected CoxNet model by comparing it with other currently available recurrence risk algorithms on a held-out test set (AFP, Model of Recurrence After Liver Transplant [MORAL], and Hazard Associated with liver Transplantation for Hepatocellular Carcinoma [HALT-HCC score]). The developed CoxNet-based recurrence prediction model showed a satisfying overall concordance score of 0.75 (95% confidence interval [CI], 0.64-0.84). In comparison, the recalibrated risk algorithms' concordance scores were as follows: AFP score 0.64 (outperformed by the CoxNet model, 1-sided 95% CI, >0.01; P = 0.04) and MORAL score 0.64 (outperformed by the CoxNet model 1-sided 95% CI, >0.02; P = 0.03). The recalibrated HALT-HCC score performed well with a concordance of 0.72 (95% CI, 0.63-0.81) and was not significantly outperformed (1-sided 95% CI, ≥0.05; P = 0.29). Developing a comprehensive posttransplantation HCC recurrence risk calculator using machine learning is feasible and can yield higher accuracy than other available risk scores. Further research is needed to confirm the utility of machine learning in this setting.

The role of graft to recipient weight ratio on enhanced recovery of the recipient after living donor liver transplantation - A systematic review of the literature and expert panel recommendations.

BACKGROUND: There continues to be debate about the lower limit of graft-to-recipient weight ratio (GRWR) for living donor liver transplant (LDLT). OBJECTIVES: To identify the lower limit of GRWR compatible with enhanced recovery after living donor liver transplant and to provide international expert panel recommendations. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Studies assessing how GRWR affects recipient outcomes such as small for size syndrome, other complications, patient and graft survival, and length of stay were included. PROTOCOL REGISTRATION: CRD42021260794. RESULTS: Twenty articles were included in the qualitative synthesis, and all were retrospective observational studies. There was heterogeneity in the definition of study cohorts and key outcome measures such as small-for-size syndrome. Most studies lacked risk adjustment given limited single-center sample size. GRWR of ≥ .8% is associated with enhanced recovery. Recipients of grafts with GRWR < .8%, however, were found to have similar outcomes as those with ≥ .8% when appropriate consideration is made for portal flow modulation and recipient illness severity. CONCLUSIONS: GRWR ≥ .8% is often compatible with enhanced recovery, but grafts < .8% can be used in selected LDLT recipients with optimal donor-recipient selection, surgical technique, and perioperative management (Quality of Evidence; Low | Grade of Recommendation; Strong).