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Background: Liver transplantation (LT) is the treatment of choice for end-stage liver disease and certain malignancies such as hepatocellular carcinoma (HCC). Data on the surgical management of de novo or recurrent tumors that develop in the transplanted allograft are limited. This study aimed to investigate the perioperative and long-term outcomes for patients undergoing hepatic resection for de novo or recurrent tumors after liver transplantation., Methods: The study enrolled adult and pediatric patients from 12 centers across North America who underwent hepatic resection for the treatment of a solid tumor after LT. Perioperative outcomes were assessed as well as recurrence free survival (RFS) and overall survival (OS) for those undergoing resection for HCC., Results: Between 2003 and 2023, 54 patients underwent hepatic resection of solid tumors after LT. For 50 patients (92.6 %), resection of malignant lesions was performed. The most common lesion was HCC (n = 35, 64.8 %), followed by cholangiocarcinoma (n = 6, 11.1 %) and colorectal liver metastases (n = 6, 11.1 %). The majority of the 35 patients underwent resection of HCC did not receive any preoperative therapy (82.9 %) or adjuvant therapy (71.4 %), with resection their only treatment method for HCC. During a median follow-up period of 50.7 months, the median RFS was 21.5 months, and the median OS was 49.6 months., Conclusion: Hepatic resection following OLT is safe and associated with morbidity and mortality rates that are comparable to those reported for patients undergoing resection in native livers. Hepatic resection as the primary and often only treatment modality for HCC following LT is associated with acceptable RFS and OS and should be considered in well selected patients., (© 2024. Society of Surgical Oncology.)

Hilar cholangiocarcinoma (hCCA) is an infiltrative disease that often presents with locally advanced and/or metastatic disease, with a minority of patients eligible for surgical resection. Select patients with unresectable hCCA, or patients with hCCA in the setting of primary sclerosing cholangitis, with tumors less than 3 cm and no evidence of extrahepatic disease, can be effectively treated with neoadjuvant chemoradiation followed by liver transplantation. Staging laparotomy documenting lack of occult metastatic disease, including a portal lymphadenectomy documenting no nodal metastases, is essential to achieve optimal outcomes. Overall 5 year survival among treated patients is approximately 60%., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Positron emission tomography myocardial perfusion imaging (PET MPI) is a noninvasive diagnostic test capable of detecting coronary artery disease, structural heart disease, and myocardial flow reserve (MFR). We aimed to determine the prognostic utility of PET MPI to predict post-liver transplant (LT) major adverse cardiac events (MACE). Among the 215 LT candidates that completed PET MPI between 2015 and 2020, 84 underwent LT and had 4 biomarker variables of clinical interest on pre-LT PET MPI (summed stress and difference scores, resting left ventricular ejection fraction, global MFR). Post-LT MACE were defined as acute coronary syndrome, heart failure, sustained arrhythmia, or cardiac arrest within the first 12 months post-LT. Cox regression models were constructed to determine associations between PET MPI variable/s and post-LT MACE. The median LT recipient age was 58 years, 71% were male, 49% had NAFLD, 63% reported prior smoking, 51% had hypertension, and 38% had diabetes mellitus. A total of 20 MACE occurred in 16 patients (19%) at a median of 61.5 days post-LT. One-year survival of MACE patients was significantly lower than those without MACE (54% vs. 98%, p =0.001). On multivariate analysis, reduced global MFR ≤1.38 was associated with a higher risk of MACE [HR=3.42 (1.23-9.47), p =0.019], and every % reduction in left ventricular ejection fraction was associated with an 8.6% higher risk of MACE [HR=0.92 (0.86-0.98), p =0.012]. Nearly 20% of LT recipients experienced MACE within the first 12 months of LT. Reduced global MFR and reduced resting left ventricular ejection fraction on PET MPI among LT candidates were associated with increased risk of post-LT MACE. Awareness of these PET-MPI parameters may help improve cardiac risk stratification of LT candidates if confirmed in future studies., (Copyright © 2023 American Association for the Study of Liver Diseases.)

The adult healthy human pancreas has been poorly studied given the lack of indication to obtain tissue from the pancreas in the absence of disease and rapid postmortem degradation. We obtained pancreata from brain dead donors, thus avoiding any warm ischemia time. The 30 donors were diverse in age and race and had no known pancreas disease. Histopathologic analysis of the samples revealed pancreatic intraepithelial neoplasia (PanIN) lesions in most individuals irrespective of age. Using a combination of multiplex IHC, single-cell RNA sequencing, and spatial transcriptomics, we provide the first-ever characterization of the unique microenvironment of the adult human pancreas and of sporadic PanIN lesions. We compared healthy pancreata to pancreatic cancer and peritumoral tissue and observed distinct transcriptomic signatures in fibroblasts and, to a lesser extent, macrophages. PanIN epithelial cells from healthy pancreata were remarkably transcriptionally similar to cancer cells, suggesting that neoplastic pathways are initiated early in tumorigenesis., Significance: Precursor lesions to pancreatic cancer are poorly characterized. We analyzed donor pancreata and discovered that precursor lesions are detected at a much higher rate than the incidence of pancreatic cancer, setting the stage for efforts to elucidate the microenvironmental and cell-intrinsic factors that restrain or, conversely, promote malignant progression. See related commentary by Hoffman and Dougan, p. 1288. This article is highlighted in the In This Issue feature, p. 1275., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: Ascites is common in cirrhosis but uncommon after liver transplant. We aimed to characterize the incidence, natural history, and current management strategies of post-transplant ascites., Methods: We performed a retrospective cohort study of patients who underwent liver transplantation at 2 centers. We included patients who underwent deceased donor whole graft liver transplants between 2002 and 2019. Chart review identified patients with post-transplant ascites, requiring a paracentesis between 1 and 6-month post-transplants. Detailed chart review identified clinical and transplant characteristics, evaluation of ascites etiology, and treatments., Results: Of 1591 patients who successfully underwent a first-time orthotopic liver transplant for chronic liver disease, 101 (6.3%) developed post-transplant ascites. Only 62% of these patients required large volume paracentesis for ascites before transplant. 36% of patients with post-transplant ascites had early allograft dysfunction. Most patients with post-transplant ascites (73%) required a paracentesis within 2 months of transplant, but 27% had delayed ascites onset. From 2002 to 2019, ascites studies were obtained less often, and hepatic vein pressure measurement was performed more often. Diuretics were the mainstay of treatment (58%). The use of albumin infusion and splenic artery embolization to treat post-transplant ascites increased over time. Larger pre-transplant spleen size was associated with a greater number of post-transplant paracenteses (r=0.32 and p=0.003). For patients who underwent splenic intervention, paracentesis frequency was significantly reduced (1.6-0.4 paracenteses/month, p=0.0001). The majority (72%) of patients had clinical resolution of their ascites at 6-month post-transplant., Conclusions: Persistent or recurrent ascites continues to be a clinical issue in the modern era of liver transplantation. Most had clinical resolution within 6 months, some requiring intervention., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Objective: Surgical videos are commonly utilized by trainees to prepare for surgical cases. However, currently available videos tend to be of excessive length, variable quality, and exist behind paywalls or in other exclusive formats. Our objective was to create a series of videos that would address these shortcomings, and further allow for dynamic engagement between learners and experts., Design: Our group created surgical videos using principles of microlearning, an educational strategy which deconstructs content into small units and uses social media platforms where learners and educators may actively engage. We published a library of short (<3 min) videos covering various steps of abdominal transplantation operations on a YouTube channel. We leveraged Twitter to disseminate the content and engage with experts and learners from around the world., Setting: Multi-institutional., Results: Over the period from July 2020 to January 2021, 24 microlearning videos were created, stored on a YouTube channel, and posted to Twitter weekly using a newly created account. During that time period, the videos, averaging 124 seconds in length, were viewed 4393 times and watched for a total of 127 hours. The account gained 611 followers in 37 countries and 37 US states with 312,400 impressions (defined as tweet views). Twitter users who engaged with our microlearning content (favorite, retweet, or reply) included faculty (27%), residents (21%), fellows (8%), and medical students (11%)., Conclusions: Broad participation with the educational material and discussion on Twitter demonstrated the potential for the microlearning technique to provide educational benefit for learners internationally. The spread of the tweets shows an opportunity to augment traditional surgical education, and the willingness of faculty to discuss alternative techniques with their peers. Our group will continue to develop a library of microlearning videos for surgical operations and engage with other institutions for collaboration and expansion., (Copyright © 2022 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Acute kidney injury (AKI) is one of the most common complications of liver transplantation (LT). We examined the impact of intraoperative management on risk for AKI following LT. In this retrospective observational study, we linked data from the electronic health record with standardized transplant outcomes. Our primary outcome was stage 2 or 3 AKI as defined by Kidney Disease Improving Global Outcomes guidelines within the first 7 days of LT. We used logistic regression models to test the hypothesis that the addition of intraoperative variables, including inotropic/vasopressor administration, transfusion requirements, and hemodynamic markers improves our ability to predict AKI following LT. We also examined the impact of postoperative AKI on mortality. Of the 598 adult primary LT recipients included in our study, 43% (n = 255) were diagnosed with AKI within the first 7 postoperative days. Several preoperative and intraoperative variables including (1) electrolyte/acid-base balance disorder (International Classification of Diseases, Ninth Revision codes 253.6 or 276.x and International Classification of Diseases, Tenth Revision codes E22.2 or E87.x, where x is any digit; adjusted odds ratio [aOR], 1.917, 95% confidence interval [CI], 1.280-2.869; p = 0.002); (2) preoperative anemia (aOR, 2.612; 95% CI, 1.405-4.854; p = 0.002); (3) low serum albumin (aOR, 0.576; 95% CI, 0.410-0.808; p = 0.001), increased potassium value during reperfusion (aOR, 1.513; 95% CI, 1.103-2.077; p = 0.01), and lactate during reperfusion (aOR, 1.081; 95% CI, 1.003-1.166; p = 0.04) were associated with posttransplant AKI. New dialysis requirement within the first 7 days postoperatively predicted the posttransplant mortality. Our study identified significant association between several potentially modifiable variables with posttransplant AKI. The addition of intraoperative data did not improve overall model discrimination., (© 2022 The Authors. Liver Transplantation published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background: The optimal cardiovascular (CV) risk stratification in liver transplant (LT) candidates remains unclear. The aim of this study was to evaluate concordance of findings between dobutamine stress echocardiography (DSE), positron emission tomography/computed tomography myocardial perfusion imaging (PET/CT MPI), and left heart catheterization in adult LT candidates., Methods: Data on 234 consecutive adult LT candidates from February 2015 to June 2018 with PET/CT MPI were reviewed. Adverse CV outcomes were adjudicated via chart review by a board-certified cardiologist., Results: Median age was 60.8, body mass index 30.2 kg/m 2 , and model of end-stage liver disease-sodium 14; 61% were male, and 54% had diabetes. Thirty-seven percent had nonalcoholic steatohepatitis and 29% alcohol-related liver disease. Sixty-five percent of patients had a DSE, of which 41% were nondiagnostic. No factors were independently associated with having a nondiagnostic DSE. The median global myocardial flow reserve correlated positively with hemoglobin and negatively with model of end-stage liver disease-sodium, age, ejection fraction, and body mass index. Moderate/high-risk MPIs were associated with older age and known CV disease. In patients with 2 cardiac testing modalities, findings were concordant in 87%. Eleven of 53 LT recipients experienced an adverse CV outcome, but no independent predictors were identified for this outcome., Conclusions: Results of different cardiac risk-stratification modalities were concordant across modalities the majority of the time in LT candidates, although these findings were not independently correlated with risk of post-LT CV outcomes. Given the high rates of nondiagnostic DSEs in this population, PET/CT MPI may be the preferred CV risk-stratification modality in older patients and those with known CV disease., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Purpose: Our purpose was to evaluate the accuracy of LI-RADS Treatment Response Algorithm (LR-TRA) for assessing the viability of hepatocellular carcinoma (HCC) treated with stereotactic body radiation therapy (SBRT), using explant pathology as the gold standard., Methods and Materials: This retrospective study included patients who underwent SBRT for locoregional treatment of HCC between 2008 and 2019 with subsequent liver transplantation. Five radiologists independently assessed all treated lesions by using the LR-TRA. Imaging and posttransplant histopathology were compared. Lesions were categorized as either completely (100%) or incompletely (<100%) necrotic, and performance characteristics and predictive values for the LR-TR viable and nonviable categories were calculated for each reader. Interreader reliability was calculated using the Fleiss kappa test., Results: A total of 40 treated lesions in 26 patients (median age, 63 years [interquartile range, 59.4-65.5]; 23 men) were included. For lesions treated with SBRT, sensitivity for incomplete tumor necrosis across readers ranged between 71% and 86%, specificity between 85% and 96%, and positive predictive value between 86% and 92%, when the LR-TR equivocal category was treated as nonviable, accounting for subject clustering. When the LR-TR equivocal category was treated as viable, sensitivity of complete tumor necrosis for lesions treated with SBRT ranged from 88% to 96%, specificity from 71% to 93%, and negative predictive value from 85% to 96%. Interreader reliability was fair (k = 0.22; 95% confidence interval, 0.13-0.33). Although a loss of arterial phase hyperenhancement (APHE) was highly correlated with pathologically nonviable tumor on explant, almost half of the patients with APHE had pathologically nonviable tumor on explant., Conclusions: LR-TRA v2018 performs well for predicting complete and incomplete necrosis in HCC treated with SBRT. In contrast to other locoregional therapies, the presence of APHE after SBRT does not always indicate viable tumor and suggests that observation may be an appropriate strategy for these patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Split-liver transplantation has allocation advantages over reduced-size transplantation because of its ability to benefit 2 recipients. However, prioritization of split-liver transplantation relies on the following 3 major assumptions that have never been tested in the United States: similar long-term transplant recipient outcomes, lower incidence of segment discard among split-liver procurements, and discard of segments among reduced-size procurements that would be otherwise "transplantable." We used United Network for Organ Sharing Standard Transplant Analysis and Research data to identify all split-liver (n = 1831) and reduced-size (n = 578) transplantation episodes in the United States between 2008 and 2018. Multivariable Cox proportional hazards modeling was used to compare 7-year all-cause graft loss between cohorts. Secondary analyses included etiology of 30-day all-cause graft loss events as well as the incidence and anatomy of discarded segments. We found no difference in 7-year all-cause graft loss (adjusted hazard ratio [aHR], 1.1; 95% confidence interval [CI], 0.8-1.5) or 30-day all-cause graft loss (aHR, 1.1; 95% CI, 0.7-1.8) between split-liver and reduced-size cohorts. Vascular thrombosis was the most common etiology of 30-day all-cause graft loss for both cohorts (56.4% versus 61.8% of 30-day graft losses; P = 0.85). Finally, reduced-size transplantation was associated with a significantly higher incidence of segment discard (50.0% versus 8.7%) that were overwhelmingly right-sided liver segments (93.6% versus 30.3%). Our results support the prioritization of split-liver over reduced-size transplantation whenever technically feasible., (Copyright © 2021 by the American Association for the Study of Liver Diseases.)

Frailty is a powerful prognostic tool in cirrhosis. Claims-based frailty scores estimate the presence of frailty without the need for in-person evaluation. These algorithms have not been validated in cirrhosis. Whether they measure true frailty or perform as well as frailty in outcome prediction is unknown. We evaluated 2 claims-based frailty scores-Hospital Frailty Risk Score (HFRS) and Claims-Based Frailty Index (CFI)-in 3 prospective cohorts comprising 1100 patients with cirrhosis. We assessed differences in neuromuscular/neurocognitive capabilities in those classified as frail or nonfrail based on each score. We assessed the ability of the indexes to discriminate frailty based on the Fried Frailty Index (FFI), chair stands, activities of daily living (ADL), and falls. Finally, we compared the performance of claims-based frailty measures and physical frailty measures to predict transplant-free survival using competing risk regression and patient-reported outcomes. The CFI identified neuromuscular deficits (balance, chair stands, hip strength), whereas the HFRS only identified poor chair-stand performance. The CFI had areas under the receiver operating characteristic curve (AUROCs) for identifying frailty as measured by the FFI, ADL, and falls of 0.57, 0.60, and 0.68, respectively; similarly, the AUROCs were 0.66, 0.63, and 0.67, respectively, for the HFRS. Claims-based frailty scores were associated with poor quality of life and sleep but were outperformed by the FFI and chair stands. The HFRS, per 10-point increase (but not the CFI) predicted survival of patients in the liver transplantation (subdistribution hazard ratio [SHR], 1.08; 95% confidence interval [CI], 1.03-1.12) and non-liver transplantation cohorts (SHR, 1.13; 95% CI, 1.05-1.22). Claims-based frailty scores do not adequately associate with physical frailty but are associated with important cirrhosis-related outcomes., (Copyright © 2021 by the American Association for the Study of Liver Diseases.)

Objective: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT)., Summary of Background Data: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate., Methods: The United States HCC LT Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS)., Results: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01)., Conclusions: The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results., Competing Interests: S. A. Shah, Veloxis Pharmaceuticals Role(s): Membership on advisory committee or review panels. Organ Recovery Systems Role(s): Other activities (please specify), Research funding. J. Emamaullee, iSPY COVID trial Role(s): Other activities (please specify), Data Monitoring Committee. Gilead Role(s): Other activities (please specify), Research funding. American Society of Transplant Surgeons Role(s): Other activities (please specify), Research funding. American Association for the Study of Liver Diseases Role(s): Other activities (please specify), Research Funding. National Cancer Institute Role(s): Other activities (please specify), Research funding. M. H. Nguyen, Gilead Role(s): Other activities (please specify), Research support. Glycotest Role(s): Other activities (please specify), Research support. National Cancer Institute Role(s): Other activities (please specify), Research support. Bayer Role(s): Consulting. Esai Role(s): Consulting. Novartis Role(s): Consulting. Gilead Role(s): Consulting. Exact Sciences Role(s): Consulting. Laboratory of Advanced Medicine Role(s): Consulting. W. C. Chapman, Novartis Role(s): Membership on advisory committee or review panels. Pathfinder Role(s): Other activities (please specify), IP royalties.; S. K. Maithel, Celgene (Bristol Meyers Squibbs). All the other authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: US liver transplant programs have traditionally been evaluated on 1-year patient and graft survival. However, there is concern that a narrow focus on recipient outcomes may not incentivize programs to improve in other ways that would benefit patients with end-stage liver disease., Objective: To determine the correlation among different potential domains of quality for adult liver transplant programs., Design, Setting, and Participants: This retrospective cohort study was conducted from 2014 to 2019 among adult liver transplant programs included in the United Network for Organ Sharing and Scientific Registry of Transplant Recipients program-specific reports. Liver transplant programs in the United States completing at least 10 liver transplants per year were included. Data were analyzed from March 2 to August 13, 2020., Main Outcomes and Measures: The potential domains of quality examined included recipient outcomes (1-year graft and patient survival), aggressiveness (ie, marginal graft use, defined as the rate of use of donors with body mass index [calculated as weight in kilograms divided by height in meters squared] greater than 40, age older than 65 years, or deceased by cardiac death), and waiting list management (ie, waiting list mortality). The correlation among measures, aggregated at the center level, was evaluated using linear regression to control for mean Model for End Stage Liver Disease-Sodium score at organ allocation. The extent to which programs were able to achieve high quality across multiple domains was also evaluated., Results: Among 114 transplant programs that performed a total of 44 554 transplants, the mean (SD) 1-year graft and patient survival was 90.3% (3.0%) with a total range of 75.9% to 96.6%. The mean (SD) waiting list mortality rate was 16.7 (6.1) deaths per 100 person-years, with a total range of 6.3 to 53.0 deaths per 100 person years. The mean (SD) marginal graft use rate was 15.8 (8.8) donors per 100 transplants, with a total range of 0 to 49.3 donors. There was no correlation between 1-year graft and patient survival and waiting list mortality (β = -0.053; P = .19) or marginal graft use (β = -0.007; P = .84) after correcting for mean allocation Model for End Stage Liver Disease-Sodium scores. There were 2 transplant programs (1.8%) that performed in the top quartile on all 3 measures, while 4 transplant programs (3.6%) performed in the bottom quartile on all 3 measures., Conclusions and Relevance: This cohort study found that among US liver transplant programs, there were no correlations among 1-year recipient outcomes, measures of program aggressiveness, or waiting list management. These findings suggest that a program's performance in one domain may be independent and unrelated to its performance on others and that the understanding of factors contributing to these domains is incomplete.

Background: Data regarding marijuana (MJ) use among liver transplant (LT) candidates are limited. We set out to determine the incidence and pre- and post-LT outcomes of adult LT candidates with a self-reported history of MJ use., Methods: Baseline clinical characteristics, waitlist, and post-LT outcomes of adult LT candidates from January 2010 to March 2017 were compared., Results: Among 2690 LT candidates, 630(23%) and 298(11%) reported a history of MJ use and use within the past 12 months, respectively. Although the proportion of MJ users increased over time(β = .76, p = .03), the proportion listed and transplanted did not change. Listing for LT increased with male (OR 1.24, 95% CI 11.01-1.52), MELD score (OR 1.08, 95% CI 1.01-1.15), HCC (OR 1.83, 95% CI 1.39-2.41) but decreased among MJ users (OR 0.67, 95% CI 0.50-0.91, p = .01). The median time to listing was longer among MJ users compared to non-users (115 vs. 87 days, p < .0005). Post-LT survival was similar in 83 MJ users and 306 non-users., Conclusion: The proportion of MJ users among LT candidates is increasing. MJ users have a greater burden of psychosocial issues which may contribute to longer evaluations and lower rate of LT listing. Post-LT survival was not impacted by self-reported MJ use history., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: There is conflicting evidence for the benefit of adjuvant radiotherapy (RT) after resection of pancreatic ductal adenocarcinoma (PDAC), especially for margin-negative (R0) resections. We aimed to evaluate the association of adjuvant RT with survival after R0 resection of PDAC., Methods: Using National Cancer Database (NCDB) data from 2004 to 2013, we identified patients with R0 resection of nonmetastatic PDAC. Patients with neoadjuvant radiotherapy and chemotherapy and survival <6 months were excluded. Propensity score matching was used to account for treatment selection bias. A multivariable Cox proportional hazards model was then used to analyze the association of RT with survival., Results: Of 4547 (36%) RT and 7925 (64%) non-RT patients, 3860 RT and 3860 non-RT patients remained in the cohort after matching. Clinicopathologic and demographic variables were well balanced after matching. Lymph node metastases were present in 68% (44% N1, 24% N2). After matching, RT was associated with higher survival (median 25.8 vs 23.9 mo, 5-yr 27% vs 24%, P < 0.001). After multivariable adjustment, RT remained associated with a survival benefit (HR 0.89, 95% CI 0.84-0.94, P < 0.001). Stratified and multivariable interaction analyses showed that this benefit was restricted to patients with node-positive disease: N1 (HR: 0.68, CI95%: 0.62-0.76, P = 0.007) and N2 (HR: 0.59, CI95%: 0.54-0.64, P = 0.04)., Conclusions: In this large retrospective cohort study, adjuvant RT after R0 PDAC resection was associated with a survival benefit in patients with node-positive disease. Adjuvant RT should be considered after R0 resection of PDAC with node-positive disease., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Organ transplant is a life-saving procedure for patients with end-stage organ failure. In the US, organ procurement organizations (OPOs) are responsible for the evaluation and procurement of organs from donors who have died; however, there is controversy regarding what measures should be used to evaluate their performance., Objective: To evaluate OPO performance metrics using combined mortality and donation data and quantify the associations of population demographics with donation metrics., Design, Setting, and Participants: This national cohort study includes data from the US organ transplantation system from January 2008 through December 2017. All individuals who died within the US, as reported by the National Death index, were included., Exposures: Death, organ donation, and donation eligibility., Main Outcomes and Measures: Evaluation of the variation in donation metrics and the use of ineligible donors by OPO and demographic subgroup., Results: This study included 17 501 742 deaths and 75 769 deceased organ donors (45 040 men [59.4%]; 51 908 White individuals [68.5%]). Of these donors, 15 857 (20.9%) were not eligible, as defined by the OPOs. The median donation metrics by OPO were 0.004 (range, 0.002-0.012) donors per death, 0.89 (range, 0.68-1.30) donors per eligible death, and 0.72 (range, 0.57-0.86) eligible donors per eligible death. The OPOs in the upper quartile of the overall eligible donors per eligible death metric were in the upper quartile of annual rankings on 90 of 140 occasions (64.3%). There was little overlap in top-performing OPOs between metrics; an OPO in the upper quartile for 1 metric was also in the upper quartile for the other metrics on 37 of 570 occasions (6.5% of the time). The median donor eligibility rate, defined as the number of eligible donors per donor, was 0.79 (range, 0.61-0.95) across OPOs. Age (eg, 65 to 84 years, coefficient, -0.55 [SE, 0.03]; P < .001; vs those aged 18 to 34 years), sex (male individuals, -0.09 [SE, 0.02]; P < .001; vs female individuals), race (eg, Black individuals, 0.35 [SE, 0.02]; P < .001; vs White individuals), cause of death (eg, central nervous system tumor, 0.48 [SE, 0.08]; P < .001; vs anoxia), year (eg, 2016-2017: -0.10 [SE, 0.03]; P < .001; vs 2008-2009), and OPO were associated with the use of ineligible donors; OPO was a significant factor associated with performance in all metrics (χ256, 500.5; P < .001; coefficient range across individual OPOs, -0.15 [SE, 0.09] to 0.75 [SE, 0.09]), even after accounting for population differences. Female and non-White individuals were significantly less likely to be used as ineligible donors., Conclusions and Relevance: We demonstrate significant variability in OPO performance rankings, depending on which donation metric is used. There were significant differences in OPO performance, even after accounting for differences in potential donor populations. Our data suggest significant variation in use of ineligible donors among OPOs, a source for increased donors. The performance of OPOs should be evaluated using a range of donation metrics.

Background: Opioid use in liver transplantation is poorly understood and has potential associated morbidity., Methods: Using a national data set of employer-based insurance claims, we identified 1257 adults who underwent liver transplantation between December 2009 and February 2015. We categorized patients based on their duration of opioid fills over the year before and after transplant admission as opioid-naive/no fills, chronic opioid use (≥120 d supply), and intermittent use (all other use). We calculated risk-adjusted prevalence of peritransplant opioid fills, assessed changes in opioid use after transplant, and identified correlates of persistent or increased opioid use posttransplant., Results: Overall, 45% of patients filled ≥1 opioid prescription in the year before transplant (35% intermittent use, 10% chronic). Posttransplant, 61% of patients filled an opioid prescription 0-2 months after discharge, and 21% filled an opioid between 10-12 months after discharge. Among previously opioid-naive patients, 4% developed chronic use posttransplant. Among patients with pretransplant opioid use, 84% remained intermittent or increased to chronic use, and 73% of chronic users remained chronic users after transplant. Pretransplant opioid use (risk factor) and hepatobiliary malignancy (protective) were the only factors independently associated with risk of persistent or increased posttransplant opioid use., Conclusions: Prescription opioid use is common before and after liver transplant, with intermittent and chronic use largely persisting, and a small development of new chronic use posttransplant. To minimize the morbidity of long-term opioid use, it is critical to improve pain management and optimize opioid use before and after liver transplant., Competing Interests: C.M.B. reports a patent for Peripheral Perineural Dexmedetomidine licensed to the University of Michigan, is a consultant for Recro Pharma and Heron Therapeutics, and has received research funding from Neuros Medical. The other authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Burnout among surgeons has been attributed to increased workload and decreased autonomy. Although prior studies have examined burnout among transplant surgeons, no studies have evaluated burnout in abdominal transplant surgery fellows. The objective of our study was to identify predictors of burnout and understand its impact on personal and patient care during fellowship. A survey was sent to all abdominal transplant surgery fellows in an American Society of Transplant Surgeons-accredited fellowship. The response rate was 59.2% (n = 77) and 22.7% (n = 17) of fellows met criteria for burnout. Fellows with lower grit scores were more likely to exhibit burnout compared with fellows with higher scores (3.6 vs 4.0, P = .026). Those with burnout were more likely to work >100 hours per week (58.8% vs 27.6%, P = .023), have severe work-related stress (58.8% vs 22.4%, P = .010), consider quitting fellowship (94.1% vs 20.7%, P < .001), or make a medical error (35.3% vs 5.2%, P = .003). This national analysis of abdominal transplant fellows found that burnout rates are relatively low, but few fellows engage in self-care. Personal and program-related factors attribute to burnout and it has unacceptable effects on patient care. Transplant societies and fellowship programs should develop interventions to give fellows tools to prevent and combat burnout., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Solid organ transplant (SOT) recipients are considered to be "vulnerable" to COVID-19 infection due to immunosuppression. To date, there are no studies that compared the disease severity of COVID-19 in SOT recipients with nontransplant patients., Methods: In this case-control study, we compared the outcomes of COVID-19 between SOT recipients and their matched nontransplant controls. The cases were all adult SOT recipients (N = 41) from our academic health center who were diagnosed with COVID-19 between March 10, 2020 and May 15, 2020 using positive reverse transcriptase polymerase chain reaction for SARS-CoV2. The controls (N = 121) were matched on age (±5 y), race, and admission status (hospital or outpatient). The primary outcome was death and secondary outcomes were severe disease, intubation and renal replacement therapy (RRT)., Results: Median age of SOT recipients (9 heart, 3 lung, 16 kidney, 8 liver, and 5 dual organ) was 60 y, 80% were male and 67% were Black. Severe disease adjusted risk of death was similar in both the groups (hazard ratio = 0.84 [0.32-2.20]). Severity of COVID-19 and intubation were similar, but the RRT use was higher in SOT (odds ratio = 5.32 [1.26, 22.42]) compared to non-SOT COVID-19 patients. Among SOT recipients, COVID-19-related treatment with hydroxychloroquine (HCQ) was associated with 10-fold higher hazard of death compared to without HCQ (hazard ratio = 10.62 [1.24-91.09])., Conclusions: Although African Americans constituted one-tenth of all SOT in our center, they represented two-thirds of COVID-19 cases. Despite high RRT use in SOT recipients, the severe disease and short-term death were similar in both groups. HCQ for the treatment of COVID-19 among SOT recipients was associated with high mortality and therefore, its role as a treatment modality requires further scrutiny., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Despite growing interest from various surgical societies and patient safety organizations, concerns remain that volume-based credentialing standards are arbitrary and may fail to recognize a surgeon's full scope of practice., Objective: To evaluate whether surgeon experience with related procedures was associated with better outcomes for pancreaticoduodenectomy compared with procedure-specific experience alone., Design, Setting, and Participants: This proof-of-concept cohort study used the all-payer State Inpatient Databases from 6 geographically diverse states to identify all operations for surgeons who performed at least 1 pancreaticoduodenectomy from January 1, 2012, to December 31, 2014. Each surgeon's mean annual volume for pancreaticoduodenectomies and related complex hepatopancreatobiliary (HPB) procedures was calculated. Outcomes for surgeons above and below a threshold of 12 pancreaticoduodenectomies per year were evaluated. Whether related HPB procedure volume was also associated with better outcomes for surgeons not meeting the procedure-specific threshold was also evaluated. Data were analyzed from March 2 through 20, 2019., Main Outcomes and Measures: Thirty-day mortality and complications., Results: The study cohort included 176 043 patients, of whom 92 064 were female (52.3%), with a mean (SD) age of 59 (17) years. Within 270 hospitals, only 54 of 1028 surgeons (5.3%) met the mean pancreaticoduodenectomy volume threshold from 2012 to 2014. In-hospital mortality after pancreaticoduodenectomy was lower for surgeons who performed 12 or more procedures per year (1.8% [95% CI, 1.1%- 2.4%] vs 4.7% [95% CI, 4.0%-5.4%]; odds ratio, 0.32; 95% CI, 0.21-0.50). However, in-hospital mortality varied 7-fold among surgeons who did not meet the threshold (1.2% [95% CI, 0.8%-1.6%] to 8.4% [95% CI, 7.9%-8.9%]). Increasing HPB case volume was associated with better outcomes for pancreaticoduodenectomy in this group. For example, surgeons performing 2 or fewer pancreaticoduodenectomies annually would need to perform an additional 27 related HPB procedures to match the in-hospital mortality rate of surgeons performing 12 or more pancreaticoduodenectomies., Conclusions and Relevance: In this proof-of-concept cohort study, few surgeons met even modest annual volume thresholds for pancreaticoduodenectomy. The findings suggest that inclusion of related procedure volumes may safely expand the cohort of surgeons credentialed to perform certain procedures under volume-based standards.

Background: The morbidity and mortality from alcohol-related liver disease (ALD) is increasing in the United States. However, little is known about gender differences in evaluation and listing for liver transplantation (LT) in patients with ALD., Methods: This is a retrospective review of adult patients with ALD evaluated for LT at a single transplant center from January 1, 2010, to March 1, 2017. Univariate, multivariate, and time-series analyses were performed., Results: Among the 949 patients with ALD evaluated, mean age was 53 years, 84% were Caucasian, and 33% were women. The median model for end-stage liver disease score was similar between the genders. Women were less likely to be listed for LT (10% versus 19%; P < 0.05). The proportion of women not listed due to active substance use was significantly higher versus men (42% versus 35%; P < 0.05), while the frequency of medical contraindications was comparable between the genders. During a median follow-up of 416 days (range: 0-2784), listed women with ALD were less likely to undergo transplantation (42% versus 47%; P < 0.05)., Conclusions: Men with ALD were 95% more likely to be listed and 105% more likely to be transplanted compared to women with ALD. While men had more lifetime substance use and related consequences, women had more psychiatric comorbidities and were less likely to be listed due to active alcohol and opioid use. Early detection and effective treatment of psychiatric and substance use disorders in women with ALD may improve their transplant eligibility.

Background: Perioperative hyperglycemia is associated with poor outcomes yet evidence to guide intraoperative goals and treatment modalities during non-cardiac surgery are lacking. End-stage liver disease is associated with altered glucose homeostasis; patients undergoing liver transplantation display huge fluctuations in blood glucose (BG) and represent a population of great interest. Here, we conduct a randomized trial to compare the effects of strict versus conventional glycemic control during orthotopic liver transplant (OLT)., Methods: Following approval by the Institutional Review Board of the University of Michigan Medical School and informed consent, 100 adult patients undergoing OLT were recruited. Patients were randomized to either strict (target BG 80-120 mg/dL) or conventional (target BG 180-200 mg/dL) BG control with block randomization for diabetic and nondiabetic patients. The primary outcomes measured were 1-year patient and graft survival assessed on an intention to treat basis. Graft survival is defined as death or needing re-transplant (www.unos.org). Three and 5-year patient and graft survival, infectious and biliary complications were measured as secondary outcomes. Data were examined using univariate methods and Kaplan-Meir survival analysis. A sensitivity analysis was performed to compare patients with a mean BG of ≤120 mg/dL and those > 120 mg/dL regardless of treatment group., Results: There was no statistically significant difference in patient survival between conventional and strict control respectively;1 year, 88% vs 88% (p-0.99), 3 years, 86% vs 84% (p- 0.77), 5 years, 82% vs 78. % (p-0.36). Graft survival was not different between conventional and strict control groups at 1 year, 88% vs 84% (p-0.56), 3 years 82% vs 76% (p-0.46), 5 years 78% vs 70% (p-0.362)., Conclusion: There was no difference in patient or graft survival between intraoperative strict and conventional glycemic control during OLT., Trial Registration: Clinical trial number and registry: www.clinicaltrials.gov NCT00780026. This trial was retrospectively registered on 10/22/2008.

Purpose: Preoperative therapy in borderline resectable pancreatic cancer (BRPC) is intended to increase R0 resection rates. An optimal approach in BRPC is yet to be defined., Methods and Materials: Patients with BRPC, confirmed adenocarcinoma, performance status ≤1, and adequate organ function enrolled in a single-institution, phase 2 trial. Patients received FOLFIRINOX × 6 cycles, then radiation therapy (50 Gy in 25 fractions) concurrent with fixed-dose rate gemcitabine (1 g/m 2 over 100 minutes) followed by 2 additional gemcitabine infusions. Computed tomography scans were performed at 2-month intervals during treatment. Patients without distant disease were offered surgical exploration. The primary objective was R0 resection rate with an alternate hypothesis of 55%. Secondary objectives included median progression-free survival (PFS), median overall survival (OS), response rate, and safety. The trial registration number is NCT01661088., Results: Twenty-five patients with median age of 60 years (range, 47-77 years) enrolled from November 2011 through January 2017. Twenty-one (84%) completed FOLFIRINOX and 19 (76%) completed all protocol therapy. Treatment-related grade 3 to 4 toxicities included neutropenia (40%), nausea and vomiting (28%), diarrhea (16%), and fatigue (12%). Eighteen patients (72%) underwent laparotomy, 13 (52%) were resected (all R0). The median PFS and OS in 25 patients were 13.1 months (95% confidence interval [CI], 7.3-24.7) and 24.4 months (95% CI, 12.6-40.0), respectively. For resected patients, median PFS was 21.6 months (95% CI, 8.2-37.1) and OS was 37.1 months (95% CI, 15.4-not reached)., Conclusions: Neoadjuvant therapy with FOLFIRINOX, followed by intensity modulated radiation therapy concurrent with fixed-dose-rate gemcitabine in BRPC is feasible and tolerated. Although the alternate hypothesis was not met, the OS of the resected cohort was favorable., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The true incidence and unique risk factors for recurrent and de novo nonalcoholic fatty liver (NAFLD) and nonalcoholic steatohepatitis (NASH) post-liver transplant (LT) remain poorly characterized. We aimed to identify the incidence and risk factors for recurrent and de novo NAFLD/NASH post-LT., Methods: MEDLINE via PubMed, Embase, Scopus, and CINAHL were searched for studies from 2000 to 2018. Risk of bias was adjudicated using the Newcastle-Ottawa Scale., Results: Seventeen studies representing 2378 patients were included. All were retrospective analyses of patients with post-LT liver biopsies, with the exception of 2 studies that used imaging for outcome assessment. Seven studies evaluated occurrence of recurrent NAFLD/NASH, 3 evaluated de novo occurrence, and 7 evaluated both recurrent and de novo. In studies at generally high or moderate risk of bias, mean 1-, 3-, and ≥5-year incidence rates may be 59%, 57%, and 82% for recurrent NAFLD; 67%, 40%, and 78% for de novo NAFLD; 53%, 57.4%, and 38% for recurrent NASH; and 13%, 16%, and 17% for de novo NASH. Multivariate analysis demonstrated that post-LT body mass index (summarized odds ratio = 1.27) and hyperlipidemia were the most consistent predictors of outcomes., Conclusions: There is low confidence in the incidence of recurrent and de novo NAFLD and NASH after LT due to study heterogeneity. Recurrent and de novo NAFLD may occur in over half of recipients as soon as 1 year after LT. NASH recurs in most patients after LT, whereas de novo NASH occurs rarely. NAFLD/NASH after LT is associated with metabolic risk factors.

Importance: Presumed consent, or an opt-out organ transplant policy, has been adopted by many countries worldwide to increase organ donation. The implication of such a policy for transplants in the United States is uncertain, however., Objective: To simulate the potential implications of a presumed consent policy in the United States., Design, Setting, and Participants: In a decision analytical model, a simulation model was developed using cohort data from January 1, 2004, to December 31, 2014, in the Organ Procurement and Transplantation Network Standard Transplant Analysis and Research files. All US patients (n = 524 359) who were on the waiting list for at least 1 solid organ and all deceased organ donors during the study period were included in the analyses. All data and statistical analyses were performed from January 30, 2019, to July 31, 2019., Main Outcomes and Measures: Increase in the organs available for donation and life-years gained associated with a 5%, 15%, or 25% increase in deceased donors, based on the published changes from a presumed consent policy., Results: This study considered 524 359 unique candidates (aged ≥18 years; 320 908 [61.2%] male) for a solid organ transplant from January 1, 2004, to December 31, 2014. With a base case scenario of a 5% presumed consent-associated increase in donors, the removals (owing to death or illness) from the waiting list for all organs would have an associated 3.2% to 10.4% mean reduction, depending on the random or ideal allocation of new organs to patients on the waiting list. Sensitivity analyses showed that waiting list removals could be decreased up to 52%; however, this reduction was not enough to completely eliminate waiting list removals during the study period. The biggest estimated increases in annual life-years gained associated with a presumed consent policy were in kidney transplant candidates (95% CIs by deceased donor increase: 5% increase, 3440-3466 years; 15% increase, 10 321-10 399 years; 25% increase, 17 201-17 332 years) and liver transplant candidates (95% CIs by deceased donor increase: 5% increase, 898-905 years; 15% increase, 2693-2714 years; 25% increase, 4448-4523 years). Adoption of a presumed consent policy could result in a 4295-year (95% CI, 4277-4313 years) to 11 387-year (95% CI, 11 339-11 435 years) increase in life-years, accounting for the survival advantages associated with a transplant., Conclusions and Relevance: In this study, presumed consent was estimated to be associated with modest but important improvement in the number of organ transplants and increases in life-years gained for patients awaiting an organ transplant. Further consideration and even debate about the ethical and public policy implications of a presumed consent policy are warranted.

Background: There is limited data on deliberate teaching of residents in the clinic setting; we sought to investigate the clinic experience at our institution and improve education through creation of a novel "Resident-Optimized Clinic" (ROC)., Methods: An online survey was sent separately to residents and faculty. Based on the results of this survey a modified ROC was developed to try to improve the obstacles to learning in clinic., Results: Qualitative analysis revealed the barriers in clinic were inconsistencies in expectations, lack of autonomy, time, and facility limitations. The modified ROC was rated positively with 100% of participants expressing they had sufficient time and autonomy; and 90% felt the environment was optimized for teaching., Conclusions: Multiple themes have been identified as problematic for the clinic education experience. The ROC was rated positively by trainees suggesting thoughtful intervention to improve clinic results in a better clinic experience and more educational gain from the clinic environment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

New-onset stage 4-5 chronic kidney disease (CKD) after liver transplantation (LT) is associated with high morbidity, mortality, and economic burden. In 2010, we instituted an early renal sparing immunosuppression (RSI) protocol for LT recipients with severe renal dysfunction (pre-LT dialysis/estimated glomerular filtration rate (eGFR)<30mL/min/1.73 m 2 or post-LT acute kidney injury) consisting of 2 doses of basiliximab for induction and delaying tacrolimus to post-LT day 4-7. We examined the effect of early RSI on post-LT renal outcomes., Methods: Data on all adults who had LT between January 1, 2010, and December 12, 2014 were collected. We calculated the renal risk index (RRI) score for each LT recipient (https://rri.med.umich.edu). Primary outcome was new-onset post-LT stage 4-5 CKD., Results: Of 214 LT recipients, 121 (57%) received early RSI and 93 (43%) received standard immunosuppression. Cumulative incidence of new-onset stage 4-5 CKD was higher in early RSI compared with standard immunosuppression ( P = 0.03). Female sex and RRI score were the significant risk factors for development of post-LT stage CKD in the entire study cohort as well as the LT recipients with RRI ≥ sixth decile (high-risk group)., Conclusions: Delaying tacrolimus initiation combined with basiliximab induction did not have a durable effect on long-term renal outcomes in high-risk LT recipients. Further studies are needed to identify the effective strategies to preserve renal function by targeting patients at high risk for CKD progression., (Copyright © 2019 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Tobacco use has been associated with poorer outcomes after liver transplantation (LT). Our study examined the effect on LT listing outcomes of a newly implemented policy prohibiting the use of all tobacco products compared with a prior restrictive policy. Medical records of consecutive adult patients evaluated for LT from January 2010 to July 2013 (era 1, n = 1344) and August 2013 to March 2017 (era 2, n = 1350) were reviewed. The proportion of LT candidates listed was the primary outcome. The mean age of the 2694 LT candidates was 54 ± 11 years, 60% were male, and the mean Model for End-Stage Liver Disease (MELD) score was 15 ± 7. Although the proportion of LT candidates who were smokers was significantly higher in era 2 (33% versus 23%; P < 0.005), the proportion of smokers listed for LT remained stable (13% versus 17%; P = 0.25). However, there were more smokers excluded for ongoing tobacco use in era 2 compared with era 1 (9.6% versus 4.4%; P = 0.001). Factors independently associated with LT listing included a diagnosis of hepatocellular carcinoma, being married, private insurance, absence of psychiatry comorbidity, and absence of tobacco, marijuana, or opiate use but evaluation during era 2 was not associated with LT listing. However, the median time to listing significantly increased over time, especially in smokers (from 65 to 122 days; P = 0.001), and this trend was independently associated with evaluation during era 2, a lower MELD score, not having children, and a lower level of education (P < 0.05). In conclusion, despite an increasing incidence of active smokers being referred for LT evaluation, the proportion of smoker candidates listed for LT was unchanged after instituting our prohibitive tobacco use policy. However, the time to get on the waiting list for smokers who were eventually listed was significantly longer due to the need to achieve complete tobacco cessation., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

Introduction: Liver transplant (LT) recipients have limited understanding of post-transplant chronic kidney disease (CKD) despite an excellent pre-existing framework of transplant care. This pilot study examined the efficacy and feasibility of a tailored educational and goal-setting tool in improving CKD knowledge among LT recipients with early-stage CKD., Methods: In this prospective cohort study, we administered the CKD educational and goal-setting tool to 81 LT recipients between 7/1/2016 and 12/31/2017. We excluded patients with simultaneous liver-kidney transplantation, eGFR<30 ml/min, non-English speaking, on hemodialysis or listed for kidney transplantation. The pre- and post-education knowledge scores were compared using a paired t-test. Linear regression was used to assess the independent predictors of change in knowledge score., Results: Mean age was 56.3 years, 69.1% were males, 85.2% were Caucasians and mean eGFR was 61.2 ± 20.0 ml/min. The CKD educational and goal-setting tool improved the CKD knowledge scores among LT recipients (pre: 71.8 ± 16.6%, post: 83.3 ± 10.4%; p<0.001). In an adjusted model (r2 = 0.75), those with lower pre-education knowledge scores had the most improvement in their post-education knowledge scores (β = -83.2; p<0.001). Two-thirds stated their most important self-management goal and reported motivation to follow this goal. Time spent for the CKD education was approximately 15 minutes., Conclusions: A simple LT-specific patient educational and goal-setting tool effectively improved CKD knowledge. Implementation of this tailored intervention will improve CKD awareness and may promote goal-setting in the target population., Competing Interests: The authors have declared that no competing interests exist.

Frailty is increasingly recognized as a predictor of poor outcomes in solid organ transplantation. The most widely utilized frailty tool, the Fried Frailty Index (FFI), includes patient-reported exhaustion, weight loss, and physical activity as well as measured walk speed and handgrip. Although hepatic encephalopathy (HE) is common among liver transplant candidates, data are lacking regarding its impact on the interpretation of frailty. We prospectively enrolled 685 patients with cirrhosis during their transplant evaluation, following them until death or transplantation. Our cohort was aged 54.5 ± 10.3 years, 60% male, with an average MELD score of 14.7 ± 6.3. A history of HE was present in 39%. Frailty was present in 41%, associated with higher MELD, low albumin, ascites, and HE. HE was associated with frail performance on three components of the FFI-grip (odds ratio 1.41 95% CI, 1.03-1.92), walk speed (1.56 95% CI, 1.14-2.15), and decreased energy (1.44 95% CI, 1.05-1.99). These three components were associated with transplant free survival in the whole cohort: energy (hazard ratio 1.67 95% CI, 1.25-2.28), grip (1.63 95% CI, 1.24-2.16), and walk speed (1.56 95% CI, 1.19-2.04). However, among patients with HE, the FFI was not associated with survival. HE plays a critical role in the frailty phenotype and the implications of frailty among patients with cirrhosis evaluated for liver transplantation., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: To reduce the geographic heterogeneity in liver transplant allocation, the United Network of Organ Sharing has proposed redistricting, which is impacted by both donor supply and liver transplantation demand. We aimed to determine the impact of demographic changes on the redistricting proposal and characterize causes behind geographic heterogeneity in donor supply., Methods: We analyzed adult donors from 2002 to 2014 from the United Network of Organ Sharing database and calculated regional liver donation and utilization stratified by age, race, and body mass index. We used US population data to make regional projections of available donors from 2016 to 2025, incorporating the proposed 8-region redistricting plan. We used donors/100 000 population age 18 to 84 years (D/100K) as a measure of equity. We calculated a coefficient of variation (standard deviation/mean) for each regional model. We performed an exploratory analysis where we used national rates of donation, utilization and both for each regional model., Results: The overall projected D/100K will decrease from 2.53 to 2.49 from 2016 to 2025. The coefficient of variation in 2016 is expected to be 20.3% in the 11-region model and 13.2% in the 8-region model. We found that standardizing regional donation and utilization rates would reduce geographic heterogeneity to 4.9% in the 8-region model and 4.6% in the 11-region model., Conclusions: The 8-region allocation model will reduce geographic variation in donor supply to a significant extent; however, we project that geographic disparity will marginally increase over time. Though challenging, interventions to better standardize donation and utilization rates would be impactful in reducing geographic heterogeneity in organ supply.