Orbitrap Mass Spectrometry and High-Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) Enable the in-Depth Analysis of Human Serum Proteoforms.

Blood serum and plasma are arguably the most commonly analyzed clinical samples, with dozens of proteins serving as validated biomarkers for various human diseases. Top-down proteomics may provide additional insights into disease etiopathogenesis since this approach focuses on protein forms, or proteoforms, originally circulating in blood, potentially providing access to information about relevant post-translational modifications, truncations, single amino acid substitutions, and many other sources of protein variation. However, the vast majority of proteomic studies on serum and plasma are carried out using peptide-centric, bottom-up approaches that cannot recapitulate the original proteoform content of samples. Clinical laboratories have been slow to adopt top-down analysis, also due to higher sample handling requirements. In this study, we describe a straightforward protocol for intact proteoform sample preparation based on the depletion of albumin and immunoglobulins, followed by simplified protein fractionation via polyacrylamide gel electrophoresis. After molecular weight-based fractionation, we supplemented the traditional liquid chromatography-tandem mass spectrometry (LC-MS2) data acquisition with high-field asymmetric waveform ion mobility spectrometry (FAIMS) to further simplify serum proteoform mixtures. This LC-FAIMS-MS2 method led to the identification of over 1000 serum proteoforms < 30 kDa, outperforming traditional LC-MS2 data acquisition and more than doubling the number of proteoforms identified in previous studies.

Intracardiac thrombosis and pulmonary thromboembolism during liver transplantation: A systematic review and meta-analysis.

Intracardiac thrombosis and/or pulmonary thromboembolism (ICT/PE) is a rare but devastating complication during liver transplantation. Its pathophysiology remains poorly understood, and successful treatment remains a challenge. This systematic review summarizes the available published clinical data regarding ICT/PE during liver transplantation. Databases were searched for all publications reporting on ICT/PE during liver transplantation. Data collected included its incidence, patient characteristics, the timing of diagnosis, treatment strategies, and patient outcomes. This review included 59 full-text citations. The point prevalence of ICT/PE was 1.42%. Thrombi were most often diagnosed during the neohepatic phase, particularly at allograft reperfusion. Intravenous heparin was effective in preventing early-stage thrombus from progressing further and restoring hemodynamics in 76.32% of patients it was utilized for; however, the addition of tissue plasminogen activator or sole use of tissue plasminogen activator offered diminishing returns. Despite all resuscitation efforts, the in-hospital mortality rate of an intraoperative ICT/PE was 40.42%, with nearly half of these patients dying intraoperatively. The results of our systematic review are an initial step for providing clinicians with data that can help identify higher-risk patients. The clinical implications of our results warrant the development of identification and management strategies for the timely and effective treatment of these tragic occurrences during liver transplantation.

Improved Label-Free Quantification of Intact Proteoforms Using Field Asymmetric Ion Mobility Spectrometry.

The high-throughput quantification of intact proteoforms using a label-free approach is typically performed on proteins in the 0-30 kDa mass range extracted from whole cell or tissue lysates. Unfortunately, even when high-resolution separation of proteoforms is achieved by either high-performance liquid chromatography or capillary electrophoresis, the number of proteoforms that can be identified and quantified is inevitably limited by the inherent sample complexity. Here, we benchmark label-free quantification of proteoforms of Escherichia coli by applying gas-phase fractionation (GPF) via field asymmetric ion mobility spectrometry (FAIMS). Recent advances in Orbitrap instrumentation have enabled the acquisition of high-quality intact and fragmentation mass spectra without the need for averaging time-domain transients prior to Fourier transform. The resulting speed improvements allowed for the application of multiple FAIMS compensation voltages in the same liquid chromatography-tandem mass spectrometry experiment without increasing the overall data acquisition cycle. As a result, the application of FAIMS to label-free quantification based on intact mass spectra substantially increases the number of both identified and quantified proteoforms without penalizing quantification accuracy in comparison to traditional label-free experiments that do not adopt GPF.

Trends and Health Care Outcomes Among Living Liver Donors: Are We Ready to Expand the Donor Pool With Living Liver Donations?

We studied the trends and various outcomes, including the readmission rates, health care utilization, and complications among living liver donors (LLDs) in the United States. We queried the National Database for data from 2010 to 2017 for all LLDs. The primary outcomes were 30-day and 90-day readmission rates. The secondary outcomes included health care use (length of stay [LOS], cost of care), index admission, and calendar-year mortality. Logistic regression models were fit for various outcomes. A total of 1316 LLDs underwent hepatectomy during the study period. The median donor age was 35.0 years (interquartile range, 27.4-43.6), and donors were predominantly women (54.2%). The trend of LLD surgeries remained stable at large medical centers (85.3%). The 30-day and 90-day readmission rates were low at 5% and 5.9%, respectively. Older age (50 years and older; 8%; confidence interval [CI], 0.6%-15.9%; P = 0.03) and hepatectomy at small to medium-sized hospitals were associated with increased index LOS (13.4%; 95% CI, 3.1%-24.7%; P = 0.01). Moreover, older age of donor (-11.3%; 95% CI, -20.3% to -1.4%; P = 0.03), Elixhauser score ≥3 (17%; 95% CI, 1.2%-35.3%; P = 0.03), and Medicaid insurance (24.5%; 95% CI, 1.2%-53.1%; P = 0.04) were also associated with increased cost. The overall rate of any complications during index admission was 42.8%. Male sex (odds ratio [OR], 1.63; 95% CI, 1.19-2.23) was an independent predictor of post-LLD complications. There was no index admission or calendar-year mortality reported during the study period. This is the largest national report of LLDs to date, showing that the trend of LLD surgeries is stable in the United States. With established safety, fewer complications, and less health care utilization, LLDs can be a potential source of continuation of liver transplantation in the context of changing liver allocation policies in the United States.

Levels of polybrominated diphenyl ethers (PBDEs) in water and sediment from open city drains in Makurdi Metropolitan Area, North Central Nigeria.

Polybrominated diphenyl ethers (PBDEs) have been classified as persistent organic pollutants (POPs) as well as endocrine-disrupting compounds (EDCs). This study determined the concentrations of six PBDE congeners (BDE 47, BDE 99, BDE 100, BDE 153, BDE 154, and BDE 183) in water and sediment samples from open city drains, in the Makurdi Metropolitan Area, North Central Nigeria, using gas chromatogragh-mass spectrometer. These congeners are components of the penta- and octa-BDE formulations that have been banned by the European Union. The samples were collected from the drains, bi-monthly, for 1 year across dry and wet seasons. All the congeners considered were found to be present in both water and sediment. The levels of Σ6PBDEs in water ranged from 0.05 to 0.28 ng L-1 during dry season and 0.02 to 0.36 ng L-1 during wet season, while their levels in sediment during dry and wet seasons ranged from 3.22 to 26.26 ng g-1 and 7.51 to 27.41 ng g-1, respectively. The percentage recoveries from solid phase and Soxhlet extractions ranged from 69 to 104% and 70 to 112%, respectively. It was concluded that the presence of all the congeners in both water and sediment posed a pollution risk to the river in which the drains discharge and require further monitoring and necessary preventive measures.

Validation of Risk Score in Predicting Early Readmissions in Decompensated Cirrhotic Patients: A Model Based on the Administrative Database.

Early readmission in patients with decompensated liver cirrhosis leads to an enormous burden on health care use. A retrospective cohort study using the 2013 and 2014 Nationwide Readmission Database (NRD) was conducted. Patients with a diagnoses of cirrhosis and at least one feature of decompensation were included. The primary outcome was to develop a validated risk model for early readmission. Secondary outcomes were to study the 30-day all-cause readmission rate and the most common reasons for readmission. A multivariable logistic regression model was fit to identify predictors of readmissions. Finally, a risk model, the Mumtaz readmission risk score, was developed for prediction of 30-day readmission based on the 2013 NRD and validated on the 2014 NRD. A total of 123,011 patients were included. The 30-day readmission rate was 27%, with 79.6% of patients readmitted with liver-related diagnoses. Age <65 years; Medicare or Medicaid insurance; nonalcoholic etiology of cirrhosis; ≥3 Elixhauser score; presence of hepatic encephalopathy, ascites, variceal bleeding, hepatocellular carcinoma, paracentesis, or hemodialysis; and discharge against medical advice were independent predictors of 30-day readmission. This validated model enabled patients with decompensated cirrhosis to be stratified into groups with low (<20%), medium, (20%-30%), and high (>30%) risk of 30-day readmissions. Conclusion: One third of patients with decompensated cirrhosis are readmitted within 30 days of discharge. The use of a simple risk scoring model with high generalizability, based on demographics, clinical features, and interventions, can bring refinement to the prediction of 30-day readmission in high-risk patients; the Mumtaz readmission risk score highlights the need for targeted interventions in order to decrease rates of readmission within this population.

County Rankings Have Limited Utility When Predicting Liver Transplant Outcomes.

BACKGROUND: Evidence of geographical differences in liver transplantation (LT) outcomes has been proposed as a reason to include community characteristics in risk adjustment of transplant quality metrics. However, consistency and utility of rankings in LT outcomes for counties have not been demonstrated. AIMS: We sought to evaluate the utility of county rankings (county socioeconomic status (SES) or county health scores (CHS)) on outcomes after LT. METHODS: Using the United Network for Organ Sharing Registry, adults ≥ 18 years of age undergoing LT between 2002 and 2014 were identified. County-specific 1-year survival was calculated using the Kaplan-Meier method for counties with ≥ 5 LT performed during this period. Agreement between high-risk designation by 1-year mortality rate and county ranking was calculated using the Spearman correlation coefficient. RESULTS: The analysis included 47,769 LT recipients in 1092 counties. County 1-year mortality rates were not correlated with county CHS (Spearman ρ = 0.01, p = 0.694) or county SES (Spearman ρ = - 0.01, p = 0.734). After controlling for individual-level covariates, a statistically significant variability in mortality hazards across counties (p < 0.001) persisted. Although both CHS and SES measures improved the model fit (p = 0.004 and p = 0.048, respectively), an unexplained residual variation in mortality hazard across counties continued. CONCLUSIONS: There is poor agreement between county rankings on various socioeconomic indicators and LT outcomes. Although there is variability in outcomes across counties, this appears not to be due to county-level socioeconomic indices.

Pull-Down of Metalloproteins in Their Native States by Using Desthiobiotin-Based Probes.

One-third of all proteins are estimated to require metals for structural stability and/or catalytic activity. Desthiobiotin probes containing metal binding groups can be used to capture metalloproteins with exposed active-site metals under mild conditions so as to prevent changes in metallation state. The proof-of-concept was demonstrated with carbonic anhydrase (CA), an open active site, Zn2+ -containing protein. CA was targeted by using sulfonamide derivatives. Linkers of various lengths and structures were screened to determine the optimal structure for capture of the native protein. The optimized probes could selectively pull down CA from red blood cell lysate and other protein mixtures. Pull-down of differently metallated CAs was also investigated.

Intrahepatic Delivery of Pegylated Catalase Is Protective in a Rat Ischemia/Reperfusion Injury Model.

BACKGROUND: Ischemia/reperfusion injury (IRI) can occur during liver surgery. Endogenous catalase is important to cellular antioxidant defenses and is critical to IRI prevention. Pegylation of catalase (PEG-CAT) improves its therapeutic potential by extending plasma half-life, but systemic administration of exogenous PEG-CAT has been only mildly therapeutic for hepatic IRI. Here, we investigated the protective effects of direct intrahepatic delivery of PEG-CAT during IRI using a rat hilar clamp model. MATERIALS AND METHODS: PEG-CAT was tested in vitro and in vivo. In vitro, enriched rat liver cell populations were subjected to oxidative stress injury (H2O2), and measures of cell health and viability were assessed. In vivo, rats underwent segmental (70%) hepatic warm ischemia for 1 h, followed by 6 h of reperfusion, and plasma alanine aminotransferase and aspartate aminotransferase, tissue malondialdehyde, adenosine triphosphate, and GSH, and histology were assessed. RESULTS: In vitro, PEG-CAT pretreatment of liver cells showed substantial uptake and protection against oxidative stress injury. In vivo, direct intrahepatic, but not systemic, delivery of PEG-CAT during IRI significantly reduced alanine aminotransferase and aspartate aminotransferase in a time-dependent manner (P < 0.01, P < 0.0001, respectively, for all time points) compared to control. Similarly, tissue malondialdehyde (P = 0.0048), adenosine triphosphate (P = 0.019), and GSH (P = 0.0015), and the degree of centrilobular necrosis, were improved by intrahepatic compared to systemic PEG-CAT delivery. CONCLUSIONS: Direct intrahepatic administration of PEG-CAT achieved significant protection against IRI by reducing the volume distribution and taking advantage of the substantial hepatic first-pass uptake of this molecule. The mode of delivery was an important factor for protection against hepatic IRI by PEG-CAT.

[D-Ala2, D-Leu5] Enkephalin Improves Liver Preservation During Normothermic Ex Vivo Perfusion.

BACKGROUND: Meeting the metabolic demands of donor livers using normothermic ex vivo liver perfusion (NEVLP) preservation technology is challenging. The delta opioid agonist [D-Ala2, D-Leu5] enkephalin (DADLE) has been reported to decrease the metabolic demand in models of ischemia and cold preservation. We evaluated the therapeutic potential of DADLE by investigating its ability to protect against oxidative stress and hepatic injury during normothermic perfusion. MATERIALS AND METHODS: Primary rat hepatocytes were used in an in vitro model of oxidative stress to determine the minimum dose of DADLE needed to induce protection and the mechanisms associated with protection. NEVLP was then used to induce injury in rat livers and determine the effectiveness of DADLE in preventing liver injury. RESULTS: In hepatocytes, DADLE was protective against oxidative stress and led to a decrease in phosphorylation of JNK and p38. Naltrindole, a δ-opioid receptor antagonist, blocked this effect. DADLE also activated the PI3K/Akt signaling pathway, and PI3K/Akt inhibition decreased the protective effects of DADLE treatment. In addition, DADLE treatment during NEVLP resulted in lower perfusate alanine aminotransferase and tissue malondialdehyde and better tissue adenosine triphosphate and glutathione. Furthermore, perfusion with DADLE compared with perfusate alone preserved tissue architecture. CONCLUSIONS: DADLE confers protection against oxidative stress in hepatocytes and during NEVLP. These data suggest that the mechanism of protection involved the prevention of mitochondrial dysfunction by opioid receptor signaling and subsequent increased expression of prosurvival/antiapoptotic signaling pathways. Altogether, data suggest that opioid receptor agonism may serve as therapeutic target for improved liver protection during NEVLP.

A validated risk model for prediction of early readmission in patients with hepatic encephalopathy.

INTRODUCTION AND AIM: Hepatic encephalopathy (HE) is a common complication in cirrhotics and is associated with an increased healthcare burden. Our aim was to study independent predictors of 30-day readmission and develop a readmission risk model in patients with HE. Secondary aims included studying readmission rates, cost, and the impact of readmission on mortality. MATERIALS AND METHODS: We utilized the 2013 Nationwide Readmission Database (NRD) for hospitalized patients with HE. A risk assessment model based on index hospitalization variables for predicting 30-day readmission was developed using multivariate logistic regression and validated with the 2014 NRD. Patients were stratified into Low Risk and High Risk groups. Cox regression models were fit to identify predictors of calendar-year mortality. RESULTS: Of 24,473 cirrhosis patients hospitalized with HE, 32.4% were readmitted within 30 days. Predictors of readmission included presence of ascites (OR: 1.19; 95% CI: 1.06-1.33), receiving paracentesis (OR: 1.43; 95% CI: 1.26-1.62) and acute kidney injury (OR: 1.11; 95% CI: 1.00-1.22). Our validated model stratified patients into Low Risk and High Risk of 30-day readmissions (29% and 40%, respectively). The cost of the first readmission was higher than index admission in the 30-day readmission cohort ($14,198 vs. $10,386; p-value <0.001). Thirty-day readmission was the strongest predictor of calendar-year mortality (HR: 4.03; 95% CI: 3.49-4.65). CONCLUSIONS: Nearly one-third of patients with HE were readmitted within 30 days, and early readmission adversely impacted healthcare utilization and calendar-year mortality. With our proposed simple risk assessment model, patients at high risk for early readmissions can be identified to potentially avert poor outcomes.

Top-Down Characterization of Heavily Modified Histones Using 193 nm Ultraviolet Photodissociation Mass Spectrometry.

The characterization of protein post-translational modifications (PTMs) remains a significant challenge for traditional bottom-up proteomics methods owing to the lability of PTMs and the difficulty of mapping combinatorial patterns of PTMs based on analysis of small peptides. These shortcomings have accelerated interest in top-down MS/MS methods that focus on analysis of intact proteins. Simultaneous mapping of all PTMs requires extensive sequence coverage to confidently localize modifications. 193 nm ultraviolet photodissociation (UVPD) has been shown to generate unparalleled sequence coverage for intact proteins compared to traditional MS/MS methods. This study focuses on identification and localization of PTMs of histones by UVPD, higher-energy collisional dissociation (HCD), and the hybrid method electron-transfer/higher-energy collision dissociation (EThcD) via a high throughput liquid chromatography-mass spectrometry strategy. In total, over 500 proteoforms were characterized among these three activation methods with 46% of the identifications found in common by two or more activation methods. EThcD and UVPD afforded more extensive characterization of proteoforms than HCD with average gains in sequence coverage of 15% and C-scores that doubled on average.

Extending Proteome Coverage by Combining MS/MS Methods and a Modified Bioinformatics Platform Adapted for Database Searching of Positive and Negative Polarity 193 nm Ultraviolet Photodissociation Mass Spectra.

To extend proteome coverage obtained from bottom-up mass spectrometry approaches, three complementary ion activation methods, higher energy collision dissociation (HCD), ultraviolet photodissociation (UVPD), and negative mode UVPD (NUVPD), are used to interrogate the tryptic peptides in a human hepatocyte lysate using a high performance Orbitrap mass spectrometer. The utility of combining results from multiple activation techniques (HCD+UVPD+NUVPD) is analyzed for total depth and breadth of proteome coverage. This study also benchmarks a new version of the Byonic algorithm, which has been customized for database searches of UVPD and NUVPD data. Searches utilizing the customized algorithm resulted in over 50% more peptide identifications for UVPD and NUVPD tryptic peptide data sets compared to other search algorithms. Inclusion of UVPD and NUVPD spectra resulted in over 600 additional protein identifications relative to HCD alone.

Impact of the new kidney allocation system A2/A2B → B policy on access to transplantation among minority candidates.

Blood group B candidates, many of whom represent ethnic minorities, have historically had diminished access to deceased donor kidney transplantation (DDKT). The new national kidney allocation system (KAS) preferentially allocates blood group A2/A2B deceased donor kidneys to B recipients to address this ethnic and blood group disparity. No study has yet examined the impact of KAS on A2 incompatible (A2i) DDKT for blood group B recipients overall or among minorities. A case-control study of adult blood group B DDKT recipients from 2013 to 2017 was performed, as reported to the Scientific Registry of Transplant Recipients. Cases were defined as recipients of A2/A2B kidneys, whereas controls were all remaining recipients of non-A2/A2B kidneys. A2i DDKT trends were compared from the pre-KAS (1/1/2013-12/3/2014) to the post-KAS period (12/4/2014-2/28/2017) using multivariable logistic regression. Post-KAS, there was a 4.9-fold increase in the likelihood of A2i DDKT, compared to the pre-KAS period (odds ratio [OR] 4.92, 95% confidence interval [CI] 3.67-6.60). However, compared to whites, there was no difference in the likelihood of A2i DDKT among minorities post-KAS. Although KAS resulted in increasing A2/A2B→B DDKT, the likelihood of A2i DDKT among minorities, relative to whites, was not improved. Further discussion regarding A2/A2B→B policy revisions aiming to improve DDKT access for minorities is warranted.

Extensive Characterization of Heavily Modified Histone Tails by 193 nm Ultraviolet Photodissociation Mass Spectrometry via a Middle-Down Strategy.

The ability to map combinatorial patterns of post-translational modifications (PTMs) of proteins remains challenging for traditional bottom-up mass spectrometry workflows. There are also hurdles associated with top-down approaches related to limited data analysis options for heavily modified proteoforms. These shortcomings have accelerated interest in middle-down MS methods that focus on analysis of large peptides generated by specific proteases in conjunction with validated bioinformatics strategies to allow quantification of isomeric histoforms. Mapping multiple PTMs simultaneously requires the ability to obtain high sequence coverage to allow confident localization of the modifications, and 193 nm ultraviolet photodissociation (UVPD) has been shown to cause extensive fragmentation for large peptides and proteins. Histones are an ideal system to test the ability of UVPD to characterize multiple modifications, as the combinations of PTMs are the underpinning of the biological significance of histones and at the same time create an imposing challenge for characterization. The present study focuses on applying 193 nm UVPD to the identification and localization of PTMs on histones by UVPD and comparison to a popular alternative, electron-transfer dissociation (ETD), via a high-throughput middle-down LC/MS/MS strategy. Histone Coder and IsoScale, bioinformatics tools for verification of PTM assignments and quantification of histone peptides, were adapted for UVPD data and applied in the present study. In total, over 300 modified forms were identified, and the distributions of PTMs were quantified between UVPD and ETD. Significant differences in patterns of PTMs were found for histones from HeLa cells prior to and after treatment with a deacetylase inhibitor. Additional fragment ion types generated by UVPD proved essential for extensive characterization of the most heavily modified forms (>5 PTMs).

Outcomes of domino liver transplantation compared to deceased donor liver transplantation: a propensity-matching approach.

Domino liver transplantation (DLT) utilizes the explanted liver of one liver transplant recipient as a donor graft in another patient. While there may be unique risks associated with DLT, it is unclear if DLT has less favorable long-term outcomes than deceased donor liver transplantation (DDLT). We used a propensity score matching approach to compare the outcomes of DLT recipients to DDLT recipients. The United Network for Organ Sharing (UNOS) registry was queried for patients undergoing DLT or DDLT in 2002-2016. Each DLT recipient was matched to a unique DDLT recipient to compare mortality and graft failure. There were 126 DLT and 62 835 DDLT recipients meeting inclusion criteria. After propensity score matching on recipient pre-transplant characteristics, 123 DLT cases were matched to DDLT controls from the same UNOS region. On stratified Cox proportional hazards regression, DLT incurred no increase in the hazard of mortality [hazard ratio (HR) = 1.4; 95% confidence interval (CI): 0.8, 2.7; P = 0.265] or graft failure (HR = 1.2; 95% CI: 0.7, 2.1; P = 0.556) compared to DDLT. Using a large national registry, a propensity-matched analysis found no increased risk of mortality or graft failure associated with DLT compared to DDLT.

County socioeconomic characteristics and pediatric renal transplantation outcomes.

BACKGROUND: Existing risk adjustment models for solid organ transplantation omit socioeconomic status (SES). With limited data available on transplant candidates' SES, linkage of transplant outcomes data to geographic SES measures has been proposed. We investigate the utility of county SES for understanding differences in pediatric kidney transplantation (KTx) outcomes. METHODS: We identified patients < 18 years of age receiving first-time KTx using United Network for Organ Sharing registry data in two eras: 2006-2010 and 2011-2015, corresponding to periods of county SES data collection. In each era, counties were ranked by 1-year rates of survival with intact graft, and by county SES score. We used Spearman correlation (ρ) to evaluate the association between county rankings on SES and transplant outcomes in each era and consistency between these measures across eras. We also evaluated the utility of county SES for improving prediction of individual KTx outcomes. RESULTS: The analysis included 2972 children and 108 counties. County SES and transplant outcomes were not correlated in either 2006-2010 (ρ = 0.06; p = 0.525) or 2011-2015 (ρ = 0.162, p = 0.093). County SES rankings were strongly correlated between eras (ρ = 0.99, p < 0.001), whereas county rankings of transplant outcomes were not correlated between eras (ρ = 0.16, p = 0.097). Including county SES quintile in individual-level models of transplant outcomes did not improve model predictive utility. CONCLUSIONS: Pediatric kidney transplant outcomes are unstable from period to period at the county level and are not correlated with county-level SES. Appropriate adjustment for SES disparities in transplant outcomes could require further collection of detailed individual SES data.

Change in Health Insurance Coverage After Liver Transplantation Can Be Associated with Worse Outcomes.

BACKGROUND: Health insurance coverage changes for many patients after liver transplantation, but the implications of this change on long-term outcomes are unclear. AIMS: To assess post-transplant patient and graft survival according to change in insurance coverage within 1 year of transplantation. METHODS: We queried the United Network for Organ Sharing for patients between ages 18-64 years undergoing liver transplantation in 2002-2016. Patients surviving > 1 year were categorized by insurance coverage at transplantation and the 1-year transplant anniversary. Multivariable Cox regression characterized the association between coverage pattern and long-term patient or graft survival. RESULTS: Among 34,487 patients in the analysis, insurance coverage patterns included continuous private coverage (58%), continuous public coverage (29%), private to public transition (8%) and public to private transition (4%). In multivariable analysis of patient survival, continuous public insurance (HR 1.29, CI 1.22, 1.37, p < 0.001), private to public transition (HR 1.17, CI 1.07, 1.28, p < 0.001), and public to private transition (HR 1.14, CI 1.00, 1.29, p = 0.044), were associated with greater mortality hazard, compared to continuous private coverage. After disaggregating public coverage by source, mortality hazard was highest for patients transitioning from private insurance to Medicaid (HR vs. continuous private coverage = 1.32; 95% CI 1.14, 1.52; p < 0.001). Similar differences by insurance category were found for death-censored graft failure. CONCLUSION: Post-transplant transition to public insurance coverage is associated with higher risk of adverse outcomes when compared to retaining private coverage.

Patients From Appalachia Have Reduced Access to Liver Transplantation After Wait-Listing.

BACKGROUND: The Appalachian region is medically underserved and characterized by high morbidity and mortality. We investigated disparities among patients listed for liver transplantation (LT) in wait-list outcomes, according to residence in the Appalachian region. METHODS: Data on adult patients listed for LT were obtained from the United Network for Organ Sharing for July 2013 to December 2015. Wait-list outcomes were compared using cause-specific hazard models by region of residence (Appalachian vs non-Appalachian) among patients listed at centers serving Appalachia. Posttransplant patient and graft survival were also compared. The study included 1835 LT candidates from Appalachia and 5200 from non-Appalachian regions, of whom 1016 patients experienced wait-list mortality or were delisted; 3505 received liver transplants. RESULTS: In multivariable analyses, patients from Appalachia were less likely to receive LT (hazard ratio [HR] = 0.86; 95% confidence interval [CI]: 0.79-0.93; P < .001), but Appalachian residence was not associated with wait-list mortality or delisting (HR = 1.03; 95% CI: 0.89-1.18; P = .696). Among liver transplant recipients, patient and graft survival did not differ by Appalachian versus non-Appalachian residence. CONCLUSION: Appalachian residence was associated with lower access to transplantation after listing for LT. This geographic disparity should be addressed in the current debate over reforming donor liver allocation and patient priority for LT.