Liver transplantation remains a life-saving therapy for a growing list of indications. Although 10,660 adult liver transplants were performed in the United States in 2023, a 50% increase over the preceding decade, the demand continues to far exceed the supply. Efforts to expand the liver donor pool by using donors that were previously considered unsuitable have remained an important strategy to help overcome shortages. We discuss the progress that has been made over the past decade, as well as potential future barriers that will need to be overcome to help successfully expand the liver donor pool.

In the United States and much of the world, prioritization for a deceased donor liver transplant focuses on sickest-first, based on allocating organs using the MELD score. There have been calls to instead allocate organs based on transplant survival benefit, but the impact of such a system on the broader waitlist population is unknown.

We performed a simulation study using the Liver Simulated Allocation Model to compare the current US system of liver allocation to the one using different time horizons, focused on pretransplant survival only, posttransplant survival only, and survival benefit (difference of posttransplant survival and pretransplant survival). Changing liver allocation to a survival benefit-based system was simulated to lead to a small improvement in average patient-level posttransplant survival (mean survival over a 5-year time horizon of 4.24 y vs. 4.19 y in the current system). However, this small improvement was associated with a simulated decrease in transplants and an increase in waitlist mortality of 400 deaths per year. The resulting net benefit overall (pretransplant deaths and posttransplant survival) was negligible under a survival benefit-based allocation approach.

Our simulations predicted that survival benefit-based allocation would only increase posttransplant survival by an average of 18 days per recipient at the expense of a simulated increase in waitlist mortality of 400 deaths per year. In the current practice of liver transplantation, with the sickest-first allocation operating in a system where transplant physicians ration organs to maximize outcomes, the overall survival benefit is maintained and not compromised.

Access to liver transplantation (LT) is affected by geographic disparities. Higher waitlist mortality is observed in patients residing farther from LT centres, but the impact of distance on post-LT outcomes is unclear.

To evaluate whether the distance LT recipients reside from their LT centre affects graft and patient outcomes.

We retrospectively studied consecutive adult patients who received deceased donor LT at a statewide LT referral centre, Royal Prince Alfred Hospital (RPAH), 2006-2021. The primary outcome was overall patient survival.

A total of 973 patients who underwent LT during the study period were analysed. The median distance from patient residence to RPAH was 44.9 km (interquartile range 21.9-168.0). Of these, 64.2% lived ≤100 km from RPAH. Compared to patients living ≤100 km from RPAH, those living >100 km away were less likely to be male, have chronic hepatitis B as their cause of liver disease or have hepatocellular carcinoma as their primary indication for LT. Living >100 km from RPAH was associated with fewer face-to-face clinic visits in the first year after LT (10 vs 11 visits, P < 0.001) and fewer readmissions to RPAH (32.4% vs 67.6%, P < 0.001). Distance from RPAH, regional code and socioeconomic code did not affect long-term graft or patient survival based on Kaplan-Meier survival analysis (log-rank P > 0.1).

In our single-centre Australian study, patients living farther from their LT centre had different demographics. Distance from the LT centre was not associated with long-term inferior graft or patient survival after LT.

End stage liver disease (ESLD) represents a growing health concern characterized by elevated morbidity and mortality, particularly among individual ineligible for liver transplantation. The demand for palliative care (PC) is pronounced in patients grappling with ESLD and acute on chronic liver failure (ACLF). Unfortunately, the historical underutilization of PC in ESLD patients, despite their substantial needs and those of their family caregivers, underscores the imperative of seamlessly integrating PC principles into routine healthcare practices across the entire disease spectrum.

To comprehensively investigate the evidence surrounding the benefits of incorporating PC into the comprehensive care plan for individuals confronting ESLD and/or ACLF.

A systematic search in the Medline (PubMed) database was performed using a predetermined search command, encompassing studies published in English without any restrictions on the publication date. Subsequently, the retrieved studies were manually examined. Simple descriptive analyses were employed to summarize the results.

The search strategies yielded 721 references. Following the final analysis, 32 full-length references met the inclusion criteria and were consequently incorporated into the study. Meticulous data extraction from these 32 studies was undertaken, leading to the execution of a comprehensive narrative systematic review. The review found that PC provides significant benefits, reducing symptom burden, depressive symptoms, readmission rates, and hospital stays. Yet, barriers like the appeal of transplants and misconceptions about PC hinder optimal utilization. Integrating PC early, upon the diagnosis of ESLD and ACLF, regardless of transplant eligibility and availability, improves the quality of life for these patients.

Despite the substantial suffering and poor prognosis associated with ESLD and ACLF, where liver transplantation stands as the only curative treatment, albeit largely inaccessible, PC services have been overtly provided too late in the course of the illness. A comprehensive understanding of PC's pivotal role in treating ESLD and ACLF is crucial for overcoming these barriers, involving healthcare providers, patients, and caregivers.

Data to guide dialysis decision-making for transplant-ineligible patients with cirrhosis are lacking.

We aimed to describe the processes, predictors, and outcomes of renal replacement therapy (RRT) initiation for transplant-ineligible patients with cirrhosis at a single liver transplantation center.

We conducted a mixed-methods study of a retrospective cohort of 372 transplant-ineligible inpatients with cirrhosis with acute kidney injury (AKI) due to hepatorenal syndrome (HRS-AKI) or acute tubular necrosis (ATN) between 2008 and 2015. We performed survival analyses to evaluate 6-month survival and renal recovery and examined end-of-life care outcomes. We used a consensus-driven medical record review to characterize processes leading to RRT initiation.

We identified 266 (71.5%) patients who received RRT and 106 (28.5%) who did not receive RRT (non-RRT). Median survival was 12.5 days (RRT) vs. 2.0 days (non-RRT) (HR 0.36, 95%CI 0.28-0.46); 6-month survival was 15% (RRT) vs. 0% (non-RRT). RRT patients were more likely to die in the intensive care unit (88% vs. 32%, p < 0.001). HRS-AKI patients were more likely to be RRT dependent at 6 months than ATN patients (86% vs. 27%, p = 0.007). The most common reasons for RRT initiation were unclear etiology of AKI on presentation (32%) and belief of likely reversibility of ATN (82%).

Most transplant-ineligible patients who were initiated on RRT experienced very short-term mortality and received intensive end-of-life care. However, approximately 1 in 6 were alive at 6 months. Our findings underscore the critical need for structured clinical processes to support high-quality serious illness communication and RRT decision-making for this population.

A new liver allocation policy was implemented by United Network for Organ Sharing (UNOS) in February 2020 with the stated intent of improving access to liver transplant (LT). There are growing concerns nationally regarding the implications this new system may have on LT costs, as well as access to a chance for LT, which have not been captured at a multicenter level.

To characterize LT volume and cost changes across the US and within specific center groups and demographics after the policy implementation.

This cross-sectional study collected and reviewed LT volume from multiple centers across the US and cost data with attention to 8 specific center demographics. Two separate 12-month eras were compared, before and after the new UNOS allocation policy: March 4, 2019, to March 4, 2020, and March 5, 2020, to March 5, 2021. Data analysis was performed from May to December 2022.

Center volume, changes in cost.

A total of 22 of 68 centers responded comparing 1948 LTs before the policy change and 1837 LTs postpolicy, resulting in a 6% volume decrease. Transplants using local donations after brain death decreased 54% (P < .001) while imported donations after brain death increased 133% (P = .003). Imported fly-outs and dry runs increased 163% (median, 19; range, 1-75, vs 50, range, 2-91; P = .009) and 33% (median, 3; range, 0-16, vs 7, range, 0-24; P = .02). Overall hospital costs increased 10.9% to a total of $46 360 176 (P = .94) for participating centers. There was a 77% fly-out cost increase postpolicy ($10 600 234; P = .03). On subanalysis, centers with decreased LT volume postpolicy observed higher overall hospital costs ($41 720 365; P = .048), and specifically, a 122% cost increase for liver imports ($6 508 480; P = .002). Transplant centers from low-income states showed a significant increase in hospital (12%) and import (94%) costs. Centers serving populations with larger proportions of racial and ethnic minority candidates and specifically Black candidates significantly increased costs by more than 90% for imported livers, fly-outs, and dry runs despite lower LT volume. Similarly, costs increased significantly (>100%) for fly-outs and dry runs in centers from worse-performing health systems.

Based on this large multicenter effort and contrary to current assumptions, the new liver distribution system appears to place a disproportionate burden on populations of the current LT community who already experience disparities in health care. The continuous allocation policies being promoted by UNOS could make the situation even worse.

Patients with mental illnesses face unique disparities in access to liver transplantation. We sought to compare rates of evaluation, transplantation, and post-transplant outcomes among patients with and without mental illnesses.

Patients aged 18-75 with decompensated cirrhosis or hepatocellular carcinoma were identified from the Medicare Standard Analytic Files from 2014-2020. Regression analyses were used to examine the association between mental illness and evaluation by a transplant surgeon, receipt of transplant, and post-transplant outcomes.

Among 274,252 liver transplant candidates, 34,269 (12.5%) patients had depression and/or anxiety disorders and 8,184 (3.0%) had severe mental illnesses. The proportion of patients evaluated by a transplant surgeon was lower among patients with severe mental illnesses (14.1%), as well as individuals with depression and/or anxiety disorders (16.0%) versus the general population (18.5%) (p < 0.001). Similarly, utilization of transplantation rates was lower among patients with severe mental illness (1.1%) compared with depression and/or anxiety disorders (2.0%), as well as individuals without mental illnesses (3.8%) (p < 0.001). On multivariable regression analyses, mental illness remained independently associated with lower odds of evaluation and transplantation among patients with mental illnesses. In contrast, on adjusted analyses there were no differences in postoperative outcomes including perioperative complications, biliary complications, graft rejection, graft failure, and overall survival.

Despite lower rates of evaluation and transplant, patients with mental illnesses did not experience differences in most postoperative outcomes compared with patients without a mental illness.

We aimed to identify variations in liver transplant access across transplant referral regions (TRRs), accounting for differences in population characteristics and practice environments. Adult end-stage liver disease (ESLD) deaths and liver waitlist additions from 2015 to 2019 were included. The primary outcome was listing-to-death ratio (LDR). We modeled the LDR as a continuous variable and obtained adjusted LDR estimates for each TRR, accounting for clinical and demographic characteristics of ESLD decedents, socioeconomic and health care environment within the TRR, and characteristics of the transplant environment. The overall mean LDR was 0.24 (range: 0.10-0.53). In the final model, proportion of patients living in poverty and concentrated poverty was negatively associated with LDR; organ donation rate was positively associated with LDR. The R2 was 0.60, indicating that 60% of the variability in LDR was explained by the model. Approximately 40% of this variation remained unexplained and may be due to transplant center behaviors amenable to intervention to improve access to care for patients with ESLD.

Background: Liver transplant is the only cure for cirrhosis. We studied the impact of palliative care on patient care by conducting a population-based cohort study. Methods: We queried the Explorys database (IBM, New York) database for a diagnosis of 'cirrhosis' followed by 'palliative care consultation' and collected demographic and clinical data. Results: We identified 316,970 patients with cirrhosis. Palliative care was consulted for 10.9% (n = 34,600) of patients. Patients aged >65 [OR 1.33 (1.30-1.36), P < .0001], men [OR 1.13 (1.11-1.16), P < .0001], a diagnosis of hepatocellular carcinoma (HCC) [OR 2.53 (2.45-2.60), P < .0001] were more likely to receive a palliative care consultation. Patients for whom palliative care were consulted were less likely to undergo surgical procedures [OR .49 (.47-.50)]. Conclusion: Only about 1 in 10 cirrhotics received a palliative care consultation. Older patients, males, and patients with a diagnosis of HCC are more likely to receive palliative care.

Patients require a clear understanding of their prognosis to make informed decisions about their care. The aim of this study was to compare the perceptions of prognosis and transplant candidacy between patients with cirrhosis and their hepatologists.

Patients with cirrhosis and their hepatologists were prospectively recruited at an urban liver transplant center. Patients and hepatologists were asked about transplant candidacy and about how many years patients would live with and without a liver transplant. Agreement between patients and hepatologists was assessed with the weighted kappa statistic. Associations between patient/hepatologists' prognostic estimates and those predicted by patients' Model for End-Stage Liver Disease-Sodium (MELD-Na) score were estimated using the Pearson correlation coefficient.

Seventy patients and 6 hepatologists were enrolled in the study. Patients were predominantly male (61.4%) and white (68.6%), with a mean MELD-Na score of 19 ± 9. There was no-slight agreement between patients and hepatologists regarding survival without and with a liver transplant (κ = 0.1 and 0.2, respectively), with patients more optimistic than their hepatologists. There was greater agreement between patients and hepatologists about transplant candidacy (κ = 0.6). There was a negligible association between MELD-Na and patient estimates (r = -0.24, P = .05) but a moderate association between MELD-Na and hepatologist estimates (r = -0.51, P < .001), with higher MELD-Na scores associated with lower predicted survival.

Patients with cirrhosis are more optimistic and less accurate in their predictions of survival compared with hepatologists, although they are more realistic about their transplant candidacy. Aligning patient and provider expectations may increase the likelihood that patients receive value-concordant care.

Cirrhosis is a major cause of death and is associated with extensive health care use. Patients with cirrhosis have complex treatment choices due to risks of morbidity and mortality. To optimally counsel and treat patients with cirrhosis requires tools to predict their longer-term liver-related survival. We sought to develop and validate a risk score to predict longer-term survival of patients with cirrhosis.

We conducted a retrospective cohort study of adults with cirrhosis with no major life-limiting comorbidities. Adults with cirrhosis within the Veterans Health Administration were used for model training and internal validation, and external validation used the OneFlorida Clinical Research Consortium. We used four model-building approaches including variables predictive of cirrhosis-related mortality, focused on discrimination at key time points (1, 3, 5, and 10 years). Among 30,263 patients with cirrhosis ≤75 years old without major life-limiting comorbidities and complete laboratory data during the baseline period, the boosted survival tree models had the highest discrimination, with 1-year, 3-year, 5-year, and 10-year survival rates of 0.77, 0.81, 0.84, and 0.88, respectively. The 1-year, 3-year, and 5-year discrimination was nearly identical in external validation. Secondary analyses with imputation of missing data and subgroups by etiology of liver disease had similar results to the primary model.

We developed and validated (internally and externally) a risk score to predict longer-term survival of patients with cirrhosis. This score would transform management of patients with cirrhosis in terms of referral to specialty care and treatment decision-making for non-liver-related care.

Much of our understanding regarding geographic issues in transplantation is based on statistical techniques that do not formally account for geography and is based on obsolete boundaries such as donation service area.

We applied spatial epidemiological techniques to analyze liver-related mortality and access to liver transplant services at the county level using data from the Centers for Disease Control and Prevention and Scientific Registry of Transplant Recipients from 2010 to 2018.

There was a significant negative spatial correlation between transplant rates and liver-related mortality at the county level (Moran's I, -0.319; P  = 0.001). Significant clusters were identified with high transplant rates and low liver-related mortality. Counties in geographic clusters with high ratios of liver transplants to liver-related deaths had more liver transplant centers within 150 nautical miles (6.7 versus 3.6 centers; P  < 0.001) compared with all other counties, as did counties in geographic clusters with high ratios of waitlist additions to liver-related deaths (8.5 versus 2.5 centers; P  < 0.001). The spatial correlation between waitlist mortality and overall liver-related mortality was positive (Moran's I, 0.060; P  = 0.001) but weaker. Several areas with high waitlist mortality had some of the lowest overall liver-related mortality in the country.

These data suggest that high waitlist mortality and allocation model for end-stage liver disease do not necessarily correlate with decreased access to transplant, whereas local transplant center density is associated with better access to waitlisting and transplant.

Acute-on-chronic liver failure (ACLF) is an acute decompensation of chronic liver disease leading to multiorgan failure and mortality. The objective of this study was to evaluate characteristics and outcomes of children with ACLF who are at the highest priority for liver transplantation (LT) on the United Network for Organ Sharing (UNOS) database-listed as status 1B. The characteristics and outcomes of 478 children with ACLF listed as status 1B on the UNOS LT waiting list from 2007-2019 were compared with children with similar or higher priority listing for transplant: 929 with acute liver failure (ALF) listed as status 1A and 808 with metabolic diseases and malignancies listed as status 1B (termed "non-ACLF"). Children with ACLF had comparable rates of cumulative organ failures compared with ALF (45% vs. 44%; p > 0.99) listings, but higher than non-ACLF (45% vs. 1%; p < 0.001). ACLF had the lowest LT rate (79%, 84%, 95%; p < 0.001), highest pre-LT mortality (20%, 11%, 1%; p < 0.001), and longest waitlist time (57, 3, 56 days; p < 0.001), and none recovered without LT (0%, 4%, 1%; p < 0.001). In survival analyses, ACLF was associated with an increased adjusted hazard ratio (HR) for post-LT mortality (HR, 1.50 vs. ALF [95% confidence interval, CI, 1.02-2.19; p = 0.04] and HR, 1.64 vs. non-ACLF [95% CI, 1.15-2.34; p = 0.01]). ACLF has the least favorable waitlist and post-LT outcomes of all patients who are status 1A/1B. Increased prioritization on the LT waiting list may offer children with ACLF an opportunity for enhanced outcomes.

Liver allocation policy was changed to reduce variance in median MELD scores at transplant (MMaT) in February 2020. "Acuity circles" replaced local allocation. Understanding the impact of policy change on donor utilization is important. Ideal (I), standard (S), and non-ideal (NI) donors were defined. NI donors include older, higher BMI donors with elevated transaminases or bilirubin, history of hepatitis B or C, and all DCD donors. Utilization of I, S, and NI donors was established before and after allocation change and compared between low MELD (LM) centers (MMaT ≤ 28 before allocation change) and high MELD (HM) centers (MMaT > 28). Following reallocation, transplant volume increased nationally (67 transplants/center/year pre, 74 post, p .0006) and increased for both HM and LM centers. LM centers significantly increased use of NI donors and HM centers significantly increased use of I and S donors. Centers further stratify based on donor utilization phenotype. A subset of centers increased transplant volume despite rising MMaT by broadening organ acceptance criteria, increasing use of all donor types including DCD donors (98% increase), increasing living donation, and transplanting more frequently for alcohol associated liver disease. Variance in donor utilization can undermine intended effects of allocation policy change.

Missed or inappropriate referrals of potential candidates for liver transplantation (LT) are common and traditional referral methods (tRs) do not allow for efficient triage. We investigated the effects of a website developed for electronic outpatient referral to LT (eRW-LT) on these issues.

We prospectively collected data on all consecutive outpatient referrals to 2 Italian LT centers from January 2015 to December 2019. In the second half of the study, starting from July 2017, referring physicians had the option of using eRW-LT, quickly obtaining the judgment on the appropriateness and urgency of the visit from a transplant hepatologist.

In the second half of the study, there were 99 eRW-LTs and 96 traditional referrals (new tRs), representing a 17.4% increase over the 161 traditional referrals (old tRs) of the first half. With eRW-LT, 11.1% of referrals were judged inappropriate online without booking a visit. Appropriateness, judged at the time of the first visit, was 59.6%, 56.2%, and 94.3% with old tRs, new tRs, and eRW-LT, respectively. Considering the appropriate visits, the median waiting time in days between referral date and first visit appointment was significantly shorter for urgent visits referred with eRW-LT (5.0; 95% CI, 4.8-9.3) compared with nonurgent visits sent with the same system (17.0; 95% CI, 11.5-25.0; P < .0001), those referred with old tRs (14.0; 95% CI, 8.0-23.0; P < .001) and with new tRs (16.0; 95% CI, 10.0-23.0; P < .001).

eRW-LT allows an increase in the number of referrals for LT, ensuring effective triage and better appropriateness of visits.

With advances in computing and information technology, large health care research databases are becoming increasingly accessible to investigators across the world. These rich, population-level data sources can serve many purposes, such as to generate "real-world evidence," to enhance disease phenotyping, or to identify unmet clinical needs, among others. This is of particular relevance to the study of patients with end-stage liver disease (ESLD), a socioeconomically and clinically heterogeneous population that is frequently under-represented in clinical trials. This review describes the recommended "best practices" in the execution, reporting, and interpretation of large database clinical epidemiology research in hepatology. The advantages and limitations of selected data sources are reviewed, as well as important concepts on data linkages. The appropriate classification of exposures and outcomes is addressed, and the strategies needed to overcome limitations of the data and minimize bias are explained as they pertain to patients with ESLD and/or liver transplantation (LT) recipients. Lastly, selected statistical concepts are reviewed, from model building to analytic decision making and hypothesis testing. The purpose of this review is to provide the practical insights and knowledge needed to ensure successful and impactful research using large clinical databases in the modern era and advance the study of ESLD and LT.

During the initial wave of the COVID-19 pandemic, organ transplantation was classified a CMS Tier 3b procedure which should not be postponed. The differential impact of the pandemic on access to liver transplantation was assessed.

Disparities in organ access and transplant outcomes among vulnerable populations have served as obstacles in liver transplantation.

Using UNOS STARfile data, adult waitlisted candidates were identified from March 1, 2020 to November 30, 2020 (n = 21,702 pandemic) and March 1, 2019 to November 30, 2019 (n = 22,797 pre-pandemic), and further categorized and analyzed by time periods: March to May (Period 1), June to August (Period 2), and September to November (Period 3). Comparisons between pandemic and pre-pandemic groups included: Minority status, demographics, diagnosis, MELD, insurance type, and transplant center characteristics. Liver transplant centers (n = 113) were divided into tertiles by volume (small, medium, large) for further analyses. Multivariable logistic regression was fitted to assess odds of transplant. Competing risk regression was used to predict probability of removal from the waitlist due to transplantation or death and sickness. Additional temporal analyses were performed to assess changes in outcomes over the course of the pandemic.

During Period 1 of the pandemic, Minorities showed greater reduction in both listing (-14% vs -12% Whites), and transplant (-15% vs -7% Whites), despite a higher median MELD at transplant (23 vs 20 Whites, P < 0.001). Of candidates with public insurance, Minorities demonstrated an 18.5% decrease in transplants during Period 1 (vs -8% Whites). Although large programs increased transplants during Period 1, accounting for 61.5% of liver transplants versus 53.4% pre-pandemic (P < 0.001), Minorities constituted significantly fewer transplants at these programs during this time period (27.7% pandemic vs 31.7% pre-pandemic, P = 0.04). Although improvements in disparities in candidate listings, removals, and transplants were observed during Periods 2 and 3, the adjusted odds ratio of transplant for Minorities was 0.89 (95% CI 0.83-0.96, P = 0.001) over the entire pandemic period.

COVID-19's effect on access to liver transplantation has been ubiquitous. However, Minorities, especially those with public insurance, have been disproportionately affected. Importantly, despite the uncertainty and challenges, our systems have remarkable resiliency, as demonstrated by the temporal improvements observed during Periods 2 and 3. As the pandemic persists, and the aftermath ensues, health care systems must consciously strive to identify and equitably serve vulnerable populations.

Advance care planning (ACP) has been shown to improve multiple outcomes in patients with serious illnesses; however, patients with advanced liver disease, or cirrhosis, rarely receive timely ACP. The purpose of this review is to evaluate the current state of ACP for patients with advanced liver disease and to provide practical guidance for integrating early ACP into routine outpatient hepatology care.

Due to multiple patient-, physician-, and systems-level barriers, patients with advanced liver disease have low rates of timely ACP engagement. Early identification and preparation of a surrogate decision-maker, enhancing clinician ACP communication skills, use of patient-centered educational tools, optimizing outpatient processes for ACP documentation, and early referral to specialty palliative care may help to improve current deficits in ACP for this population.

Provision of early ACP to patients with advanced liver disease may better ensure that patients receive medical care that is consistent with their goals and values.

This study aims to identify clinical and imaging prognosticators associated with the successful bridging or downstaging to liver transplantation (LT) in patients undergoing Yttrium-90 radioembolization (Y90-RE) for hepatocellular carcinoma (HCC).

Retrospectively, patients with Y90-RE naïve HCC who were candidates or potential candidates for LT and underwent Y90-RE were included. Patients were then divided into favorable (maintained or achieved Milan criteria (MC) eligibility) or unfavorable (lost eligibility or unchanged MC ineligibility) cohorts based on changes to their MC eligibility after Y90-RE. Penalized logistic regression analysis was performed to identify the significant baseline prognosticators.

Between 2013 and 2018, 135 patients underwent Y90-RE treatment. Among the 59 (42%) patients within MC, LT eligibility was maintained in 49 (83%) and lost in 10 (17%) patients. Within the 76 (56%) patients outside MC, eligibility was achieved in 32 (42%) and unchanged in 44 (58%). Among the 81 (60%) patients with a favorable response, 16 (20%) went on to receive LT. Analysis of the baseline characteristics revealed that lower Albumin-Bilirubin score, lower Child-Pugh class, lower Barcelona Clinic Liver Cancer stage, HCC diagnosis using dynamic contrast-enhanced imaging on CT or MRI, normal/higher albumin levels, decreased severity of tumor burden, left lobe HCC disease, and absence of HBV-associated cirrhosis, baseline abdominal pain, or fatigue were all associated with a higher likelihood of bridging or downstaging to LT eligibility (p's < 0.05).

Certain baseline clinical and tumor characteristics are associated with the successful bridging or downstaging of potential LT candidates with HCC undergoing Y90-RE.

The burden of end-of-life care for patients with cirrhosis is increasing in the US, and most of these patients, many of whom are not candidates for liver transplant, die in institutions receiving aggressive care. Advance care planning (ACP) has been associated with improved end-of-life outcomes for patients with other chronic illnesses, but it has not been well-characterized in patients with decompensated cirrhosis.

To describe the experience of ACP in patients with decompensated cirrhosis at liver transplant centers.

For this multicenter qualitative study, face-to-face semistructured interviews were conducted between July 1, 2017, and May 30, 2018, with clinicians and patients with decompensated cirrhosis at 3 high-volume transplant centers in California. Patient participants were adults and had a diagnosis of cirrhosis, at least 1 portal hypertension-related complication, and current or previous Model for End-Stage Liver Disease with sodium score of 15 or higher. Clinician participants were health care professionals who provided care during the illness trajectory.

Experiences with ACP reported by patients and clinicians. Participants were asked about the context, behaviors, thoughts, and decisions concerning elements of ACP, such as prognosis, health care preferences, values and goals, surrogate decision-making, and documentation.

The study included 42 patients (mean [SD] age, 58.2 [11.2] years; 28 men [67%]) and 46 clinicians (13 hepatologists [28%], 11 transplant coordinators [24%], 9 hepatobiliary surgeons [20%], 6 social workers [13%], 5 hepatology nurse practitioners [11%], and 2 critical care physicians [4%]). Five themes that represent the experiences of ACP were identified: (1) most patient consideration of values, goals, and preferences occurred outside outpatient visits; (2) optimistic attitudes from transplant teams hindered the discussions about dying; (3) clinicians primarily discussed death as a strategy for encouraging behavioral change; (4) transplant teams avoided discussing nonaggressive treatment options with patients; and (5) surrogate decision makers were unprepared for end-of-life decision-making.

This study found that, despite a guarded prognosis, patients with decompensated cirrhosis had inadequate ACP throughout the trajectory of illness until the end of life. This finding may explain excessively aggressive life-sustaining treatment that patients receive at the end of life.

Data have demonstrated state-wide variability in mortality rates from liver disease (cirrhosis + hepatocellular carcinoma), but data are lacking at the local level (eg, county) to identify factors associated with variability in liver disease-related mortality and hotspots of liver disease mortality.

We used Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research data from 2009 to 2018 to calculate county-level, age-adjusted liver disease-related death rates. We fit multivariable linear regression models to adjust for county-level covariates related to demographics (ie, race and ethnicity), medical comorbidities (eg, obesity), access to care (eg, uninsured rate), and geographic (eg, distance to closest liver transplant center) variables. We used optimized hotspot analysis to identify clusters of liver disease mortality hotspots based on the final multivariable models.

In multivariable models, 61% of the variability in among-county mortality was explained by county-level race/ethnicity, poverty, uninsured rates, distance to the closest transplant center, and local rates of obesity, diabetes, and alcohol use. Despite adjustment, significant within-state variability in county-level mortality rates was found. Of counties in the top fifth percentile (ie, highest mortality) of fully adjusted mortality, 60% were located in 3 states: Oklahoma, Texas, and New Mexico. Adjusted mortality rates were highly spatially correlated, representing 5 clusters: South Florida; Appalachia and the eastern part of the Midwest; Texas and Oklahoma; New Mexico, Arizona, California, and southern Oregon; and parts of Washington and Montana.

Our data demonstrate significant intrastate differences in liver disease-related mortality, with more than 60% of the variability explained by patient demographics, clinical risk factors for liver disease, and access to specialty liver care.

Differences in local organ supply and demand have introduced geographic inequities in the Model for End-stage Liver Disease (MELD) score-based liver allocation system, prompting national debate and patient-initiated lawsuits. No study to our knowledge has quantified the sex disparities in allocation associated with clinical vs geographic characteristics.

To estimate the proportion of sex disparity in wait list mortality and deceased donor liver transplant (DDLT) associated with clinical and geographic characteristics.

This retrospective cohort study used adult (age ≥18 years) liver-only transplant listings reported to the Organ Procurement and Transplantation Network from June 18, 2013, through March 1, 2018.

Liver transplant waiting list.

Primary outcomes included wait list mortality and DDLT. Multivariate Cox proportional hazards regression models were constructed, and inverse odds ratio weighting was used to estimate the proportion of disparity across geographic location, MELD score, and candidate anthropometric and liver measurements.

Among 81 357 adults wait-listed for liver transplant only, 36.1% were women (mean [SD] age, 54.7 [11.3] years; interquartile range, 49.0-63.0 years) and 63.9% were men (mean [SD] age, 55.7 [10.1] years; interquartile range, 51.0-63.0 years). Compared with men, women were 8.6% more likely to die while on the waiting list (adjusted hazard ratio [aHR], 1.11; 95% CI, 1.04-1.18) and were 14.4% less likely to receive a DDLT (aHR, 0.86; 95% CI, 0.84-0.88). In the geographic domain, organ procurement organization was the only variable that was significantly associated with increased disparity between female sex and wait list mortality (22.1% increase; aHR, 1.22; 95% CI, 1.09-1.30); no measure of the geographic domain was associated with DDLT. Laboratory and allocation MELD scores were associated with increases in disparities in wait list mortality: 1.14 (95% CI, 1.09-1.19; 50.1% increase among women) and DDLT: 0.87 (95% CI, 0.86-0.88; 10.3% increase among women). Candidate anthropometric and liver measurements had the strongest association with disparities between men and women in wait list mortality (125.8% increase among women) and DDLT (49.0% increase among women).

Our findings suggest that addressing geographic disparities alone may not mitigate sex-based disparities, which were associated with the inability of the MELD score to accurately estimate disease severity in women and to account for candidate anthropometric and liver measurements in this study.

Over the past several years, single- and multi-center case series have reported on the successful use of livers from hepatitis C virus (HCV)-antibody positive and HCV-viremic donors to HCV-negative recipients. Several authors have studied not only the efficacy of this practice but also its cost-effectiveness of transplanting HCV-infected organs to HCV-negative donors. However, previous studies had limited follow-up and had not examined transplants beyond the beginning of 2018. Using national data from 2014-2018, Thuluvath et al. demonstrated that post-transplant outcomes of recipients from either HCV-antibody and/or HCV-viremic donors were not different than those using livers from HCV-negative donors.

As the coronavirus disease 2019 (COVID-19) outbreak has rapidly evolved into a global pandemic, abdominal organ transplantation programs are currently facing multiple challenges. Transplant candidates and recipients are considered high-risk populations for severe disease and death due to COVID-19 as a result of their numerous underlying comorbidities, advanced age and impaired immune function. Emerging reports of atypical and delayed clinical presentations in these patients generate further concerns for widespread disease transmission to medical personnel and the community. The striking similarities between COVID-19 and other outbreaks that took place over the past two decades, like Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome, highlight the severity of the situation and dictate that extra measures should be taken by the transplant programs to avoid adverse outcomes. Transplant organizations are currently calling for strict screening and isolation protocols to be established in all transplant programs, for both organ donors and recipients. As the situation escalates, more radical measures might be necessary, including a temporary hold on non-urgent transplantations, resulting in serious ethical dilemmas between the survival of these patients and the safety of the community. Further data about these special populations could result in more individualized guidelines for abdominal organ transplantation in the era of COVID-19.

Despite significant morbidity and mortality among patients with decompensated cirrhosis, reported rates of advance directive (AD) completion and goals of care discussions (GCDs) between patients and providers are very low. We aimed to improve these rates by implementing a hepatologist-led advance care planning (ACP) intervention.

Rates of AD and GCD completion, as well as self-reported barriers to ACP.

Provider-led ACP in patients with decompensated cirrhosis without a prior documented AD.

Sixty-two patients were seen over 115 clinic visits. After the intervention, AD completion rates increased from 8% to 31% and GCD completion rates rose from 0% to 51%. Women (P = 0.048) and nonmarried adults (P = 0.01) had greater changes in AD completion compared to men and married adults, respectively. Needing more time during visits was seen as the major barrier to ACP among providers.

Addressing provider and system-specific barriers dramatically improved documentation rates of ACP.

The Organ Procurement and Transplantation Network implemented Share 35 on June 18, 2013, to broaden deceased donor liver sharing within regional boundaries. We investigated whether increased sharing under Share 35 impacted geographic disparity in deceased donor liver transplantation (DDLT) across donation service areas (DSAs).

Using Scientific Registry of Transplant Recipients June 2009 to June 2017, we identified 86 083 adult liver transplant candidates and retrospectively estimated Model for End-Stage Liver Disease (MELD)-adjusted DDLT rates using nested multilevel Poisson regression with random intercepts for DSA and transplant program. From the variance in DDLT rates across 49 DSAs and 102 programs, we derived the DSA-level median incidence rate ratio (MIRR) of DDLT rates. MIRR is a robust metric of heterogeneity across each hierarchical level; larger MIRR indicates greater disparity.

MIRR was 2.18 pre-Share 35 and 2.16 post-Share 35. Thus, 2 candidates with the same MELD in 2 different DSAs were expected to have a 2.2-fold difference in DDLT rate driven by geography alone. After accounting for program-level heterogeneity, MIRR was attenuated to 2.10 pre-Share 35 and 1.96 post-Share 35. For candidates with MELD 15-34, MIRR decreased from 2.51 pre- to 2.27 post-Share 35, and for candidates with MELD 35-40, MIRR increased from 1.46 pre- to 1.51 post-Share 35, independent of program-level heterogeneity in DDLT. DSA-level heterogeneity in DDLT rates was greater than program-level heterogeneity pre- and post-Share 35.

Geographic disparity substantially impacted DDLT rates before and after Share 35, independent of program-level heterogeneity and particularly for candidates with MELD 35-40. Despite broader sharing, geography remains a major determinant of access to DDLT.

Recent OPTN proposals to address geographic disparity in liver allocation have involved circular boundaries: the policy selected 12/17 allocated to 150-mile circles in addition to DSAs/regions, and the policy selected 12/18 allocated to 150-mile circles eliminating DSA/region boundaries. However, methods to reduce geographic disparity remain controversial, within the OPTN and the transplant community. To inform ongoing discussions, we studied center-level supply/demand ratios using SRTR data (07/2013-06/2017) for 27 334 transplanted deceased donor livers and 44 652 incident waitlist candidates. Supply was the number of donors from an allocation unit (DSA or circle), allocated proportionally (by waitlist size) to the centers drawing on these donors. We measured geographic disparity as variance in log-transformed supply/demand ratio, comparing allocation based on DSAs, fixed-distance circles (150- or 400-mile radius), and fixed-population (12- or 50-million) circles. The recently proposed 150-mile radius circles (variance = 0.11, P = .9) or 12-million-population circles (variance = 0.08, P = .1) did not reduce the geographic disparity compared to DSA-based allocation (variance = 0.11). However, geographic disparity decreased substantially to 0.02 in both larger fixed-distance (400-mile, P < .001) and larger fixed-population (50-million, P < .001) circles (P = .9 comparing fixed distance and fixed population). For allocation circles to reduce geographic disparities, they must be larger than a 150-mile radius; additionally, fixed-population circles are not superior to fixed-distance circles.

Allocation of livers for transplantation faces regulatory pressure to move toward broader sharing. A current proposal supported by the United Network for Organ Sharing Board of Directors relies on concentric circles, but its effect on socioeconomic inequities in access to transplant services is poorly understood. In this article, we offer a proposal that uses the state of donation as a unit of distribution, given that the state is a recognized unit of legal jurisdiction and socioeconomic health in many contexts. The Scientific Registry of Transplant Recipients liver simulated allocation model algorithm was used to generate comparative estimates of regional transplant volume and the impact of these considered changes with regard to vulnerable and high-risk patients on the waiting list and to disparities in wait-list access. State-based liver distribution outperforms the concentric circle models in overall system efficiency, reduced discards, and minimized flights for organs. Furthermore, the efflux of organs from areas of greater sociodemographic vulnerability and lesser wait-list access is more than 2-fold lower in a state-based model than in concentric circle alternatives. In summary, we propose that a state-based system offers a legally defensible, practical, and ethically sound alternative to geometric zones of organ distribution.

Liver transplantation was made a reality through the bravery, innovation, and persistence of Dr. Thomas Starzl. His death in 2017, at the age of 90, makes us pause to consider how far the field has come since its inception by this remarkable pioneer. It also is an opportunity to evaluate the continued novel innovations which contribute to the growth and potential for liver transplantation in the future. The liver transplant community in 2017 continued to be most significantly challenged by an overwhelming disparity between the need for liver transplant and the shortage of donor organs. The many ways in which this critical shortage are being addressed are examined in this article. The continued debate about equitable and efficacious organ allocation, "the liver wars," has dominated much of the recent past, while efforts to optimize current organ availability have also been aggressively pursued. Efforts to optimize the use of marginal and expanded criteria organs have escalated in recent years and have been accompanied by rigorous scientific evaluation. The ongoing opioid epidemic, combined with the approval and availability of highly effective hepatitis C treatment options, has allowed the increased use of HCV positive organs in HCV positive and negative recipients. Machine perfusion, both cold and warm, has moved solidly into the liver transplant world potentiating optimization of marginal donors and also offering potential modulation of liver grafts (ie, gene therapy, stem cell therapy, and defatting). Finally, pharmacological and mechanical interventions in DCD procurement techniques have contributed to improved outcomes in DCD transplants. All of these are explored in this article as a tribute to innovative spirit of Dr. Starzl and his continued impact on liver transplant today.

The present document is a second contribution collecting the recommendations of an expert panel of transplant hepatologists appointed by the Italian Association for the Study of the Liver (AISF) concerning the management of certain aspects of liver transplantation, including: the issue of prompt referral; the management of difficult candidates; malnutrition; living related liver transplants; hepatocellular carcinoma; and the role of direct acting antiviral agents before and after transplantation. The statements on each topic were approved by participants at the AISF Transplant Hepatology Expert Meeting organized by the Permanent Liver Transplant Commission in Mondello on 12-13 May 2017. They are graded according to the GRADE grading system.

While regional organ availability dominates discussions of distribution policy, community-level disparities remain poorly understood. We studied micro-geographic determinants of survival risk and their distribution across Donor Service Areas (DSAs). Scientific Registry of Transplant Recipients records for all adults waitlisted for liver transplantation 2002-2014 were reviewed. The primary exposure variables were county-level sociodemographic risk, as measured by the Community Health Score (CHS), a previously-validated composite index local health conditions, and distance to listing transplant center. Among 114 347 patients, the median CHS was 19.4 (range: 0-40). Compared the lowest risk counties (CHS 1-10), highest-risk counties (CHS 31-40) had more black (14.6% vs. 5.4%), publicly insured (44.9% vs. 33.0), and remote candidates (34.0% vs. 15.1% living >100 miles away). Higher-CHS candidates had greater waitlist mortality in Cox multivariable (HR 1.16 for CHS 31-40, 95% CI 1.11-1.21) and competing risks analysis (sHR 1.07, 95% CI 0.99-1.14). Post-transplant survival was similar across CHS quartiles. Living >25 miles from the transplant center conferred excess mortality risk (sHR 1.08, 95% CI 1.03-1.12). Proposed distribution changes would disproportionately impact DSAs with more high-CHS or distant candidates. Low-income, rural and minority patients experience excess mortality while awaiting transplant, and risk disproportionately worse outcomes with reduced organ availability under current proposals.

Policymakers are deliberating reforms to reduce geographic disparity in liver allocation. Public comments and the United Network for Organ Sharing Liver and Intestinal Committee have expressed interest in refining the neighborhoods approach. Share 35 and Share 15 policies affect geographic disparity.

We construct concentric neighborhoods superimposing the current 11 regions. Using concepts from concentric circles, we construct neighborhoods for each donor service area (DSA) that consider all DSAs within 400, 500, or 600 miles as neighbors. We consider limiting each neighborhood to 10 DSAs and use no metrics for liver supplies and demands. We change Model for End-Stage Liver Disease (MELD) thresholds for the Share 15 policy to 18 or 20 and apply 3- and 5-point MELD proximity boosts to enhance local priority, control travel distances, and reduce disparity. We conduct simulations comparing current allocation with the neighborhoods and sharing policies.

Concentric neighborhoods structures provide an array of solutions where simulation results indicate that they reduce geographic disparity, annual mortalities, and the airplane travel distances by varying degrees. Tuning of the parameters and policy combinations can lead to beneficial improvements with acceptable transplant volume loss and reductions in geographic disparity and travel distance. Particularly, the 10-DSA, 500-mile neighborhood solution with Share 35, Share 15, and 0-point MELD boost achieves such while limiting transplant volume losses to below 10%.

The current 11 districts can be adapted systematically by adding neighboring DSAs to improve geographic disparity, mortality, and airplane travel distance. Modifications to Share 35 and Share 15 policies result in further improvements. The solutions may be refined further for implementation.

Recently, a redistricting proposal intended to equalize Model for End-stage Liver Disease score at transplant recommended expanding liver sharing to mitigate geographic variation in liver transplantation. Yet, it is unclear whether variation in liver availability is arbitrary and a disparity requiring rectification or reflects differences in access to care. We evaluate the proposal's claim that organ supply is an "accident of geography" by examining the relationship between local organ supply and the uneven landscape of social determinants and policies that contribute to differential death rates across the United States. We show that higher mortality leading to greater availability of organs may in part result from disproportionate risks incurred at the local level. Disparities in public safety laws, health care infrastructure, and public funding may influence the risk of death and subsequent availability of deceased donors. These risk factors are disproportionately prevalent in regions with high organ supply. Policies calling for organ redistribution from high-supply to low-supply regions may exacerbate existing social and health inequalities by redistributing the single benefit (greater organ availability) of greater exposure to environmental and contextual risks (e.g. violent death, healthcare scarcity). Variation in liver availability may not be an "accident of geography" but rather a byproduct of disadvantage.

Geographic variation in liver transplantation has been the subject of extensive scrutiny, reflecting concerns that location is unfairly determinative for people needing organ transplantation. Drawing upon a number of established ethical approaches, we examine whether geographic differences in access to livers are inherently unethical.

We posit that the ethical imperative for redistribution largely hinges upon the belief that access to organs systematically disadvantages certain identifiable groups of patients over others. Yet, our data suggest that regions likely to be net-contributors may suffer from less access to transplantation and other health services, fewer social protections and greater burden of liver disease. Drawing upon a number of ethical approaches, including strict egalitarianism, utilitarianism, Maximin, Reciprocity, Sen's Impartial Spectator and a health equity framework, we demonstrate that the current proposal has significant weaknesses, and may not achieve its goals of improving equity and efficiency.

Formulating effective policies and programs to ameliorate health inequalities requires an understanding of the interrelated causes of mortality disparities and specific interventions to mitigate these causes. Although our analysis does not indicate how ethically distribute livers, but it suggests that this be done with consideration for population-based health measures.

Concurrent to development of more effective drugs for treatment of hepatitis C virus (HCV) infection, there has been an increase in the incidence of nonalcoholic fatty liver disease. Data indicate that liver transplantation prolongs survival times of patient with acute hepatitis associated with alcoholic liver disease (ALD). We compared data on disease prevalence in the population with data from liver transplantation waitlists to evaluate changes in the burden of liver disease in the United States.

We collected data on the prevalence of HCV from the 2010 and 2013-2014 cycles of the National Health and Nutrition Examination Survey. We also collected data from the HealthCore Integrated Research Database on patients with cirrhosis and chronic liver failure (CLF) from 2006 through 2014, and data on patients who received transplants from the United Network for Organ Sharing from 2003 through 2015. We determined percentages of new waitlist members and transplant recipients with HCV infection, stratified by indication for transplantation, modeling each calendar year as a continuous variable using the Spearman rank correlation, nonparametric test of trends, and linear regression models.

In an analysis of data from the National Health and Nutrition Examination Survey (2013-2014), we found that the proportion of patients with a positive HCV antibody who had a positive HCV RNA was 0.5 (95% confidence interval, 0.42-0.55); this value was significantly lower than in 2010 (0.64; 95% confidence interval, 0.59-0.73) (P = .03). Data from the HealthCore database revealed significant changes (P < .05 for all) over time in percentages of patients with compensated cirrhosis (decreases in percentages of patients with cirrhosis from HCV or ALD, but increase in percentages of patients with cirrhosis from nonalcoholic steatohepatitis [NASH]), CLF (decreases in percentages of patients with CLF from HCV or ALD, with an almost 3-fold increase in percentage of patients with CLF from NASH), and hepatocellular carcinoma (HCC) (decreases in percentages of patients with HCC from HCV or ALD and a small increase in HCC among persons with NASH). Data from the United Network for Organ Sharing revealed that among patients new to the liver transplant waitlist, or undergoing liver transplantation, for CLF, there was a significant decrease in the percentage with HCV infection and increases in percentages of patients with nonalcoholic fatty liver disease or ALD. Among patients new to the liver transplant waitlist or undergoing liver transplantation for HCC, proportions of those with HCV infection, nonalcoholic fatty liver disease, or ALD did not change between 2003 and 2015.

In an analysis of 3 different databases (National Health and Nutrition Examination Survey, HealthCore, and United Network for Organ Sharing), we found the proportion of patients on the liver transplant waitlist or undergoing liver transplantation for chronic HCV infection to be decreasing and fewer patients to have cirrhosis or CLF. However, the percentages of patients on the waitlist or receiving liver transplants for NASH or ALD are increasing, despite different relative burdens of disease among the entire population of patients with cirrhosis.