Waiting List For Liver Transplantation Research Articles

Use of endoscopic band ligation alone and in combination with nonselective beta blockers for prevention of variceal bleeding in ascites patients on the liver transplant waiting list

Objective: to conduct a comparative analysis of the effectiveness of two methods – endoscopic band ligation (EBL) alone and in combination with nonselective beta blockers (NSBB) – used for prevention of variceal bleeding (VB); to evaluate their impact on patient survival in severe ascites during long-term stay on the liver transplant waiting list (LTWL). Materials and methods. A retrospective comparative study of two groups of patients with decompensated liver disease, ascites and varices included in the LTWL, who received EBL (n = 41, group 1) and EBL + NSBB (n = 45, group 2). Results. The groups being compared did not differ in demographics, clinical parameters, MELD and Child–Turcotte–Pugh scores. There were no significant differences in the incidence of severe ascites, particularly diuretic-resistant ascites. The study groups did not differ in the incidence of mediumand large-sized varices. Incidence of bleeding did not differ in both groups. Overall mortality was significantly higher in the EBL + NSBB group than in the EBL group. Patient survival was lower, while mortality was higher in the EBL + NSBB group. The combined therapy group had a significantly higher number of acute kidney injury (AKI) than the EBL group. Conclusion. The compared methods are equivalently effective in preventing VB in patients with decompensated cirrhosis with a prolonged stay on the waiting list. Survival rate is significantly lower, while mortality is significantly higher in the EBL + NSBB group than in the EBL group.

Low Utilization of External Beam Radiation Therapy for Patients With Unresectable Hepatocellular Carcinoma: An Analysis of the United Network for Organ Sharing Database

External beam radiation therapy (EBRT) is a safe and emerging bridging liver-directed therapy (LDT) to liver transplant (LT) for patients with hepatocellular carcinoma (HCC). The prevalence and clinical characteristics of patients receiving EBRT as an LDT for LT have not been evaluated. Our aim was to describe the utilization of EBRT in patients with HCC evaluated for LT in the United States. We analyzed United Network for Organ Sharing data from October 2013 to June 2020 and identified patients with HCC who applied for model for end-stage liver disease (MELD) exceptions for LT wait list prioritization. The primary outcome was the period prevalence of EBRT. We examined associations between clinical variables and EBRT and fit survival models with EBRT as a time-varying predictor. We identified 18,543 patients with HCC with MELD exception applications. EBRT was used in 658 patients (3.5%) either alone (1.2%) or combined with other LDT (2.3%). Transarterial chemoembolization was the most used LDT (59.3%), followed by thermal ablation (27.9%) and radioembolization (15.2%). EBRT prevalence rose by an average of 12.2% per year (P=.001). Use of EBRT differed by geographic region, ranging from 2% to 8% (P < .001). EBRT and no EBRT groups had similar initial MELD score, portal vein thrombosis, tumor diameter, number of tumors, bilirubin, and α-fetoprotein (P > .05). Median time-to-transplant from wait list registration for EBRT versus no EBRT groups was 10 months (95% confidence interval, 9.4-10.9) versus 11.9 months (95% confidence interval, 11.7-12.2; P < .001). Evaluated as a time-varying predictor, EBRT increased the risk of LT by 30% (sub-hazard ratio, 1.30; P < .001), while the effect of EBRT on the risk of wait list removal due to clinical deterioration or death (sub-hazard ratio, 1.07; P=.489) was nonsignificant. In the United States, EBRT is rarely used compared with other LDTs and exhibits geographic variation. Low EBRT utilization highlights a gap in the treatment armamentarium for HCC.

Use of neural network models to predict liver transplantation waitlist mortality.

Current liver transplantation (LT) organ allocation relies on Model for End-Stage Liver Disease-sodium scores to predict mortality in patients awaiting LT. This study aims to develop neural network (NN) models that more accurately predict LT waitlist mortality. The study evaluates patients listed for LT between February 27, 2002, and June 30, 2021, using the Organ Procurement and Transplantation Network/United Network for Organ Sharing registry. We excluded patients listed with Model for End-Stage Liver Disease (MELD) exception scores and those listed for multiorgan transplant, except for liver-kidney transplant. A subset of data from the waiting list was used to create a mortality prediction model at 90days after listing with 105,140 patients. A total of 28 variables were selected for model creation. The data were split using random sampling into training, validation, and test data sets in a 60:20:20 ratio. The performance of the model was assessed using area under the receiver operating curve (AUC-ROC) and area under the precision-recall curve (AUC-PR). AUC-ROC for 90-day mortality was 0.936 (95% confidence interval [CI], 0.934-0.937), and AUC-PR was 0.758 (95% CI, 0.754-0.762). The NN 90-day mortality model outperformed MELD-based models for both AUC-ROC and AUC-PR. The 90-day mortality model specifically identified more waitlist deaths with a higher recall (sensitivity) of 0.807 (95% CI, 0.803-0.811) versus 0.413 (95% CI, 0.409-0.418; p<0.001). The performance metrics were compared by breaking the test data set into multiple patient subsets by ethnicity, gender, region, age, diagnosis group, and year of listing. The NN 90-day mortality model outperformed MELD-based models across all subsets in predicting mortality. In conclusion, organ allocation based on NN modeling has the potential to decrease waitlist mortality and lead to more equitable allocation systems in LT.

Outcomes Analyses of Pediatric Acute Liver Failure Subjects Listed for Liver Transplantation.

We characterized recent outcomes in US pediatric acute liver failure (PALF) subjects listed for liver transplantation (LT) using the Scientific Registry of Transplant Recipients (SRTR) database. Pediatric subjects listed for LT from 2002 to 2015 were assigned to the "PALF" group based on status 1/1A listing, INR >2, no hepatic artery thrombosis, and no primary graft nonfunction (N = 397). Subjects were assigned to the "non-PALF" group if listed with any status other than 1/1A (N = 4509). The PALF group had more infants <3 months of age and males at listing for LT compared to the non-PALF group. Two-thirds of PALF subjects had an indeterminate etiology. LT waitlist survival was significantly worse in the PALF group compared to the non-PALF group. Likelihood of removal from the LT waitlist for being "too sick" was higher, while that of removal for "spontaneous recovery" was lower in PALF subjects. Post-LT short-term (30 days) and long-term (60 months) outcomes were also significantly worse in PALF versus non-PALF subjects. PALF subjects who underwent living-donor-liver-transplant (LDLT) had similar LT waitlist times and post-LT survival compared to those undergoing deceased-donor-liver-transplant (DDLT). Over the study period, we observed a decreased number of liver transplants, and increase in LT waitlist- and short-term post-LT-survival in PALF subjects. LT waitlist and post-LT outcomes are worse in PALF subjects compared to non-PALF subjects. PALF subjects who undergo LDLT have similar waitlist times and post-LT outcomes compared to those undergoing DDLT.

Early Impact of MMaT-3 Policy on Liver Transplant Waitlist Outcomes for Hepatocellular Carcinoma.

Background.To reduce the disparity in access to liver transplant (LT), United Network for Organ Sharing implemented an exception policy in May 2019, which capped hepatocellular carcinoma (HCC) exception score to the median Model for End-Stage Liver Disease (MELD) at transplant within the donor service area minus 3 points (MMaT-3) after the 6-mo wait period. We aimed to evaluate how this policy affected HCC waitlist outcomes.Methods.Using United Network for Organ Sharing data, we analyzed waitlist outcomes in HCC patients at the time they received exception points from in the pre-MMaT era (August 15, 2017, to November 15, 2018) and MMaT era (June 1, 2019, to August 30, 2020). Comparisons were made within the HCC group and HCC versus non-HCC (at time of listing) groups in the pre-MMaT and MMaT eras and regions were grouped as low, medium, and high MELD based on MMaT.Results.HCC group: LT probability within HCC patients decreased by 20% (subhazard ratio [sHR], 0.78; 95% confidence interval [CI], 0.74-0.85) between the eras and decreased by 41% in low MELD regions (sHR, 0.59; 95% CI, 0.52-0.66). Waitlist dropout was unchanged. Matched HCC versus non-HCC groups: HCC patients had 80% higher LT probability (sHR, 1.84; 95% CI, 1.71-1.99) than non-HCC patients in the pre-MMaT era; which decreased to a 14% higher LT probability in MMaT era. In low and medium regions, HCC patients had over twofold higher LT probability in the pre-MMaT era, which decreased to a ~20% higher probability (sHR, 1.14; 95% CI, 1.06-1.23) in the MMaT era. After implementation of the acuity circle policy, HCC patients had lower LT probability (sHR, 0.84; 95% CI, 0.74-0.94) than non-HCC patients.Conclusions.The geographic disparity between HCC and non-HCC patients has improved with the MMaT-3 policy. Despite lower LT probability for HCC patients, waitlist dropout was not adversely impacted.

Rising Trend in Waitlisting for Alcoholic Hepatitis With More Favorable Outcomes Than Other High Model for End-stage Liver Disease in the Current Era.

In the appropriate candidate, liver transplantation (LT) is a viable treatment for alcoholic hepatitis (AH). We compared the waitlisting trends and outcomes of AH patients in the context of others with high Model for End-stage Liver Disease (MELD) score. LT listings for AH between January 1, 2008, and June 12, 2020 were identified in the United Network for Organ Sharing database. Temporal trends in listings for AH were assessed. Covariate adjusted competing risks models evaluated waitlist mortality and LT rates between AH candidates and others with listing native MELD ≥30. Between 2008 and 2019, waitlist additions for AH increased 6.5-fold. Waiting time for AH candidates was short (median 10 d). Delisting for clinical improvement was infrequent in AH, albeit higher than MELD ≥30 patients (3.3% versus 0.8%; P < 0.001). Among 99 centers with ≥1 AH listing, AH patients accounted for 0.2%-18.2% of all alcohol-related listings and 0.6%-25.0% of those with native listing MELD ≥30. Overall listing volume was larger at these 99 centers than the 40 with no AH listings (P < 0.001). AH candidates in 2014-2020 experienced improved waitlist survival (adjusted subhazard ratio, 0.67; 95% confidence interval, 0.52-0.86; P = 0.002) and higher transplant rates (adjusted subhazard ratio, 1.14; 95% confidence interval, 1.04-1.25; P = 0.006) versus other MELD ≥30 candidates. There has been a rising trend in waitlisting patients with AH and high MELD score. Liver disease causes influence waitlist outcomes and those of AH candidates are more favorable. Further research and allocation adjustments may be needed to ensure equitable organ allocation, based on liver disease cause, for those on the LT waitlist.

Sarcopenia HIBA score predicts sarcopenia and mortality in patients on the liver transplant waiting list.

Sarcopenia is a prevalent condition that predicts prognosis in patients awaiting liver transplantation (LT). The gold standard for the diagnosis of sarcopenia is the assessment of the muscular area at L3 with computed tomography (CT) scan (skeletal muscle index [SMI]), but the routine use of CT scan is limited in clinical practice. Thus, we designed a single‐center observational study aimed to evaluate the clinical factors associated with the presence of sarcopenia by SMI, and to build a score capable of predicting or excluding the presence of sarcopenia in patients on the LT waiting list (WL). Binary logistic regression analysis was performed to establish the factors independently associated with sarcopenia, and the Sarcopenia Hospital Italiano de Buenos Aires (HIBA) score was built from the resulting model after internal validation analysis by bootstrapping and correction for optimism. The predictive capability of mortality on the WL was evaluated with competing risk regression analysis. A total of 215 patients with cirrhosis on the LT WL were included. The independent factors associated with the presence of sarcopenia were male sex (odds ratio [OR]: 6.09, p < 0.001), body mass index (OR: 0.74, p < 0.001), Child Pugh (OR: 1.44, p < 0.001), and the ratio creatinine/Cystatin C (OR: 0.03, p = 0.007). The Sarcopenia HIBA score constructed with these variables showed an area under the curve of 0.862. During follow‐up, 77 (36%) patients underwent LT, 46 (21%) died, and 92 (43%) remained alive. After adjusting for Model for End‐Stage Liver Disease–Sodium, Sarcopenia HIBA score was an independent predictor of WL mortality (subhazard ratio: 1.19; 95% confidence interval 1.01–1.40; p = 0.042). Sarcopenia HIBA score is an easy‐to‐use, objective, and reliable diagnostic and predictive tool that can be useful to improve the prognostic evaluation and allow identifying a group of patients with a higher risk of death while awaiting LT.

OPTN/SRTR 2020 Annual Data Report: Liver

This year was marked by the COVID-19 pandemic, which altered transplant program activity and affected waitlist and transplant outcomes. Still, 8906 liver transplants were performed, an all-time high, across 142 centers in the United States, and pretransplant as well as graft and patient survival metrics, continued to improve. Living donation activity decreased after several years of growth. As of June 30, 2020, 98989 liver transplant recipients were alive with a functioning graft, and in the context of increasing liver transplant volume, the size of both the adult and pediatric liver transplant waitlists have decreased. On February 4, 2020, shortly before the pandemic began, a new liver distribution policy based on acuity circles was implemented, replacing donor service area- and region-based boundaries. A policy change to direct pediatric livers to pediatric recipients led to an increase in deceased donor transplant rates and a decrease in pretransplant mortality rate among children, although the absolute number of pediatric transplants did not increase in 2020. Among adults, alcohol-associated liver disease became the predominant indication for liver transplant in 2020. After implementation of the National Liver Review Board and lower waitlist priority for most exception cases in 2019, fewer liver transplants were being performed via exception points, and the transplant rate between those with and without hepatocellular carcinoma has equalized. Women continue to experience higher pretransplant mortality and lower rates of liver transplant than men.

Liver transplant allocation policies and outcomes in United States: A comprehensive review.

Liver transplant allocation policies in the United States has evolved over 3 decades. The donor liver organs are matched, allocated and procured by the Organ Procurement and Transplantation Network which is administered by the United Network of Organ Sharing (UNOS), a not-for-profit organization governed by the United States human health services. We reviewed the evolution of liver transplant allocation policies. Prior to 2002, UNOS used Child-Turcotte-Pugh score to list and stratify patients for liver transplantation (LT). After 2002, UNOS changed its allocation policy based on model for end-stage liver disease (MELD) score. The serum sodium is the independent indicator of mortality risk in patients with chronic liver disease. The priority assignment of MELD-sodium score resulted in LT and prevented mortality on waitlist. MELD-Sodium score was implemented for liver allocation policy in 2016. Prior to the current and most recent policy, livers from adult donors were matched first to the status 1A/1B patients located within the boundaries of the UNOS regions and donor-service areas (DSA). We reviewed the disadvantages of the DSA-based allocation policies and the advantages of the newest acuity circle allocation model. We then reviewed the standard and non-standard indications for MELD exceptions and the decision-making process of the National Review Liver Review Board. Finally, we reviewed the liver transplant waitlist, donation and survival outcomes in the United States.

Machine learning to predict waitlist dropout among liver transplant candidates with hepatocellular carcinoma.

BackgroundAccurate prediction of outcome among liver transplant candidates with hepatocellular carcinoma (HCC) remains challenging. We developed a prediction model for waitlist dropout among liver transplant candidates with HCC.MethodsThe study included 18,920 adult liver transplant candidates in the United States listed with a diagnosis of HCC, with data provided by the Organ Procurement and Transplantation Network. The primary outcomes were 3‐, 6‐, and 12‐month waitlist dropout, defined as removal from the liver transplant waitlist due to death or clinical deterioration.ResultsUsing 1,181 unique variables, the random forest model and Spearman's correlation analyses converged on 12 predictive features involving 5 variables, including AFP (maximum and average), largest tumor size (minimum, average, and most recent), bilirubin (minimum and average), INR (minimum and average), and ascites (maximum, average, and most recent). The final Cox proportional hazards model had a concordance statistic of 0.74 in the validation set. An online calculator was created for clinical use and can be found at: http://hcclivercalc.cloudmedxhealth.com/.ConclusionIn summary, a simple, interpretable 5‐variable model predicted 3‐, 6‐, and 12‐month waitlist dropout among patients with HCC. This prediction can be used to appropriately prioritize patients with HCC and their imminent need for transplant.

Liver transplant in children and adults with cystic fibrosis: Impact of growth failure and nutritional status

Nutritional status is known to strongly predict health outcomes in people with cystic fibrosis (CF), but the prevalence of and consequences for CF children with growth failure and underweight CF adults on the liver transplant (LT) waitlist has not been delineated. We utilized UNOS registry data from 2003 to 2017 to investigate the impact of growth failure and underweight on outcomes in liver transplant candidates with CF. Almost 1 in 3 children and adults with CF had growth failure or were underweight, respectively, at listing. Body mass index under-estimated growth failure compared to height and weight z-scores for children. In multivariate analysis of children, growth failure (HR 2.1, 95% CI 1.7-2.6), and CF (HR 2.7, 95% CI 1.6-4.6, vs. Non-CF) were independent risk factors for waitlist death among children; having both increased death risk almost fourfold (SHR 3.88, 95% CI 1.42-10.58). However, among children who did receive a LT, CF was not associated with death within 1-year post-LT. Underweight adult CF candidates were less likely to receive LT, again suggesting the importance of nutritional evaluation and early intervention in this at-risk cohort.

Oncofetal Protein CRIPTO Is Involved in Wound Healing and Fibrogenesis in the Regenerating Liver and Is Associated with the Initial Stages of Cardiac Fibrosis.

Oncofetal protein, CRIPTO, is silenced during homeostatic postnatal life and often re-expressed in different neoplastic processes, such as hepatocellular carcinoma. Given the reactivation of CRIPTO in pathological conditions reported in various adult tissues, the aim of this study was to explore whether CRIPTO is expressed during liver fibrogenesis and whether this is related to the disease severity and pathogenesis of fibrogenesis. Furthermore, we aimed to identify the impact of CRIPTO expression on fibrogenesis in organs with high versus low regenerative capacity, represented by murine liver fibrogenesis and adult murine heart fibrogenesis. Circulating CRIPTO levels were measured in plasma samples of patients with cirrhosis registered at the waitlist for liver transplantation (LT) and 1 year after LT. The expression of CRIPTO and fibrotic markers (αSMA, collagen type I) was determined in human liver tissues of patients with cirrhosis (on a basis of viral hepatitis or alcoholic disease), in cardiac tissue samples of patients with end-stage heart failure, and in mice with experimental liver and heart fibrosis using immuno-histochemical stainings and qPCR. Mouse models with experimental chronic liver fibrosis, induced with multiple shots of carbon tetrachloride (CCl4) and acute liver fibrosis (one shot of CCl4), were evaluated for CRIPTO expression and fibrotic markers. CRIPTO was overexpressed in vivo (Adenoviral delivery) or functionally sequestered by ALK4Fc ligand trap in the acute liver fibrosis mouse model. Murine heart tissues were evaluated for CRIPTO and fibrotic markers in three models of heart injury following myocardial infarction, pressure overload, and ex vivo induced fibrosis. Patients with end-stage liver cirrhosis showed elevated CRIPTO levels in plasma, which decreased 1 year after LT. Cripto expression was observed in fibrotic tissues of patients with end-stage liver cirrhosis and in patients with heart failure. The expression of CRIPTO in the liver was found specifically in the hepatocytes and was positively correlated with the Model for End-stage Liver Disease (MELD) score for end-stage liver disease. CRIPTO expression in the samples of cardiac fibrosis was limited and mostly observed in the interstitial cells. In the chronic and acute mouse models of liver fibrosis, CRIPTO-positive cells were observed in damaged liver areas around the central vein, which preceded the expression of αSMA-positive stellate cells, i.e., mediators of fibrosis. In the chronic mouse models, the fibrosis and CRIPTO expression were still present after 11 weeks, whereas in the acute model the liver regenerated and the fibrosis and CRIPTO expression resolved. In vivo overexpression of CRIPTO in this model led to an increase in fibrotic markers, while blockage of CRIPTO secreted function inhibited the extent of fibrotic areas and marker expression (αSMA, Collagen type I and III) and induced higher proliferation of residual healthy hepatocytes. CRIPTO expression was also upregulated in several mouse models of cardiac fibrosis. During myocardial infarction CRIPTO is upregulated initially in cardiac interstitial cells, followed by expression in αSMA-positive myofibroblasts throughout the infarct area. After the scar formation, CRIPTO expression decreased concomitantly with the αSMA expression. Temporal expression of CRIPTO in αSMA-positive myofibroblasts was also observed surrounding the coronary arteries in the pressure overload model of cardiac fibrosis. Furthermore, CRIPTO expression was upregulated in interstitial myofibroblasts in hearts cultured in an ex vivo model for cardiac fibrosis. Our results are indicative for a functional role of CRIPTO in the induction of fibrogenesis as well as a potential target in the antifibrotic treatments and stimulation of tissue regeneration.

Comments on "Regulations and Procurement Surgery in DCD Liver Transplantation: Expert Consensus Guidance From the International Liver Transplantation Society".

To the Editor: We read with great interest the article by Hessheimer et al titled “Regulations and Procurement Surgery in DCD Liver Transplantation: Expert Consensus Guidance From the International Liver Transplantation Society.”1 The authors summarize relevant literature and provide guidelines for donation after circulatory death (DCD) liver transplant procurement on behalf of the International Liver Transplantation Society (ILTS). Our research group recently emphasized the variations in DCD organ procurement policies in the United States with a national organ procurement organization (OPO) survey.2 We discovered tremendous disparities across regions that frequently diverged from American Society for Transplant Surgeons (ASTS) recommendations for DCD procurement and the latest consensus in the literature. It is paramount to optimize graft utilization and outcomes to meet the high demand for transplantable organs and growing waitlist. We commend the authors for their important contributions. We highlight the role of asystolic wait time in DCD liver procurement that was not addressed in the work and provide observations on DCD liver transplant (LT) and machine perfusion (MP) from the United States. Our OPO survey underscored the variations in the mandatory asystolic observation period. Despite current ASTS recommendation of a 2-min waiting time, there is little standardization across institutions that vary between 2 and 5 min. Similarly, other publications have demonstrated the lack of standardization in the declaration of circulatory death.3 Additional guidance by the ILTS on these topics would optimize DCD liver procurement process to further reduce warm ischemic times and ultimately improve patient outcomes. Currently, 11 high-volume transplant centers perform nearly half (46.3%) of all DCD LT in the United States.4 However, recent changes to the allocation policies will result in wider sharing of DCD organs and increase distribution to lower volume centers. This will undoubtedly place greater emphasis on procedures to maintain outcomes, such as broader use of hypothermic machine perfusion and normothermic machine perfusion in LT. Machine perfusion with LT has shown promising results in the United States. One investigation discovered no difference in patient survival in ex vivo MP despite substantially longer CIT.5 MP has the potential to significantly improve DCD liver procurement and reduce discard rates. In 2019 alone, 1945 potential DCD livers were not transplanted including 306 grafts, which were discarded after recovery. The trend of increasing DCD LT in the United States has been accompanied with 30% discard rate compared with 7.1% for DBD LT.5 Furthermore, one center reported that only 47.9% of DCD liver offers resulted in a successful procurement, compared with 92.3% for DBD.6 Nasralla et al demonstrated 50% reduction in graft injury, discard, and postreperfusion injury rates in an normothermic machine perfusion clinical trial.7 A publication by the Groningen group on dual hypothermic oxygenated MP highlighted lower rates of nonanastomotic biliary strictures, postreperfusion syndrome, and early graft dysfunction compared with static cold storage in DCD LT.8 MP could remarkably impact the American LT waitlist by increasing potential DCD livers that are transplanted. We congratulate Hessheimer et al on their valuable contributions. We are pleased to see the growing support for procurement procedures such as withdrawal of life support treatment in the operating room and premortem heparin administration. Despite strong surgeon preference for both of these, our survey revealed that 26 OPO did not have specific regulations on the location of withdrawal of life support treatment and 3 OPO prohibited heparin use.2,3 We hope that the ILTS recommendations lead to updates in DCD procurement protocol and regulations to comply with the latest evidence in the literature. We hope to see more analyses of liver perfusion solutions and the various additives. We anticipate similar best practice guidance by the ASTS for normothermic and hypothermic regional perfusion in liver transplantation in the near future. Reduction in variable DCD liver recovery will be tremendously impactful in increasing the utilization of DCD livers and reducing graft discard rates.

Recovery From Dialysis-Treated Acute Kidney Injury in Patients With Cirrhosis: A Population-Based Study

The decision to initiate kidney replacement therapy (KRT) for acute kidney injury (AKI) in cirrhosis remains controversial because it is unclear which patients will benefit. We sought to characterize factors associated with recovery from KRT-treated AKI in patients with cirrhosis to inform shared clinical decision-making. Population-based retrospective cohort study. Adult patients from Ontario, Canada, identified using administrative data to have cirrhosis at the time of hospital admission with AKI (based on serum creatinine level) who were treated with KRT (January 1, 2009, to December 31, 2016) and followed up until the end of2017. Demographic characteristics and comorbidities before admission. Kidney recovery defined as the absence of KRT for at least 30 days. The cumulative incidences of kidney recovery, death, and liver transplant were calculated at 1, 3, 6, and 12 months, and independent predictors of kidney recovery were evaluated using Fine and Gray competing risk regression models that generated subdistribution hazards ratios (sHRs). Overall, 722 patients were included (median age, 61 [interquartile range, 54-68] years; Model for End-Stage Liver Disease (MELD)-Na score, 26 [interquartile range, 22-34]; 66% were male; 52% had viral hepatitis, 25% nonalcoholic fatty liver disease, 18% alcohol-associated liver disease). The cumulative incidences of kidney recovery at 1, 3, 6, and 12 months were 3%, 22%, 25%, and 26%, respectively. Higher MELD-Na score (sHR per 5 units greater, 0.72 [95% CI, 0.65-0.80]), acute-on-chronic liver failure (sHR, 0.61 [95% CI, 0.43-0.86]), and sepsis (sHR, 0.57 [95% CI, 0.41-0.81]) were associated with a lower hazard of kidney recovery, whereas those on a liver transplant waitlist (sHR, 3.10 [95% CI, 1.96-4.88]) and who were admitted to a teaching hospital (sHR, 1.48 [95% CI, 1.05-2.08]) were more likely to experience kidney recovery. Observational design, AKI etiology not identified. Kidney recovery from KRT occurred in only one quarter of patients and was very unlikely after 3 months. These findings provide information regarding prognosis that may guide decisions regarding KRT initiation and continuation.

Inactive status is an independent predictor of liver transplant waitlist mortality and is associated with a transplant centers median meld at transplant.

BackgroundApproximately 30% of patients on the liver transplant waitlist experience at least one inactive status change which makes them temporarily ineligible to receive a deceased donor transplant. We hypothesized that inactive status would be associated with higher mortality which may differ on a transplant centers’ or donor service areas’ (DSA) Median MELD at Transplant (MMaT).MethodsMulti-state models were constructed (OPTN database;06/18/2013-06/08/2018) using DSA-level and transplant center-level data where MMaT were numerically ranked and categorized into tertiles. Hazards ratios were calculated between DSA and transplant center tertiles, stratified by MELD score, to determine differences in inactive to active transition probabilities.Results7,625 (30.2% of sample registrants;25,216 total) experienced at least one inactive status change in the DSA-level cohort and 7,623 experienced at least one inactive status change in the transplant-center level cohort (30.2% of sample registrants;25,211 total). Inactive patients with MELD≤34 had a higher probability of becoming re-activated if they were waitlisted in a low or medium MMaT transplant center or DSA. Transplant rates were higher and lower re-activation probability was associated with higher mortality for the MELD 26–34 group in the high MMaT tertile. There were no significant differences in re-activation, transplant probability, or waitlist mortality for inactivated patients with MELD≥35 regardless of a DSA’s or center’s MMaT.ConclusionThis study shows that an inactive status change is independently associated with waitlist mortality. This association differs by a centers’ and a DSAs’ MMaT. Prioritization through care coordination to resolve issues of inactivity is fundamental to improving access.

Excess liver transplant waitlist mortality for patients with primary biliary cholangitis under MELD-Na allocation.

Historically, patients with primary biliary cholangitis (PBC) experience waitlist mortality and low rates of liver transplant (LT). Herein, the impact of MELD-Na based allocation on PBC waitlist mortality was examined. Adult patients with PBC were compared to those with alcohol-related liver disease (ALD) or non-alcoholic steatohepatitis (NASH) listed for LT from 2013 to 2019 in OPTN. Competing risk regression evaluated waitlist mortality in the MELD and MELD-Na eras using propensity score weights. Overall, 1508 patients with PBC, 13581 with ALD, and 10455 with NASH were examined. In the MELD-Na era, 24-month cumulative incidence of waitlist mortality for PBC was 23.0% (95%CI 19.7-26.5%), ALD 13.9% (95%CI 13.1-14.8%), and NASH 20.0% (95%CI 18.9-21.2%). Using propensity score weights, adjusted risk of waitlist mortality was higher for PBC versus ALD (HR=1.45, 95%CI 1.22-1.71) and NASH (HR=1.32, 95%CI 1.14-1.55). Furthermore, among PBC, waitlist mortality risk per five-point elevation in MELD-Na (HR=1.22, 95%CI 1.11-1.35) and Karnofsky score ≤30% (HR=2.02, 95%CI 1.39-2.92) was significantly higher than among ALD (HR=1.08, 95%CI 1.04-1.13; HR=1.28, 95%CI 1.10-1.49) and NASH (HR=1.05, 95%CI 1.00-1.09; HR=1.16, 95%CI .99-1.37; all P-interactions<.05). The MELD-Na score continues to underestimate risk of waitlist death for patients with PBC relative to ALD and NASH and highlights need for additional score modifications or exceptions.

An Analysis of Free-Text Refusals as an Indicator of Readiness to Accept Organ Offers in Liver Transplantation.

Racial/ethnic minorities experience higher rates of wait‐list mortality and longer waiting times on the liver transplant wait list. We hypothesized that racial/ethnic minorities may encounter greater logistical barriers to maintaining “readiness” on the wait list, as reflected in offer nonacceptance. We identified all candidates who received an organ offer between 2009 and 2018 and investigated candidates who did not accept an organ offer using a free‐text refusal reason associated with refusal code 801. We isolated patients who did not accept an organ offer due to “candidate‐related logistical reasons” and evaluated their characteristics. We isolated 94,006 “no 801” patients and 677 “with 801 logistical” patients. Common reasons for offer decline among the 677 were 60% “unable to travel/distance,” 22% “cannot be contacted,” 13% “not ready/unspecified,” and 5% “financial/insurance.” Compared to “no 801,” “with 801 logistical” patients were more likely to be Hispanic (19% vs. 15%, P < 0.01). Multivariate logistic modeling showed Hispanic (odds ratio [OR] 1.44, 95% confidence interval [CI] 1.17‐1.76, P < 0.01) and multiracial/other ethnicity (OR 1.82, 95% CI 1.08‐3.05, P = 0.02) were associated with “with 801 logistical” status. The “with 801 logistical” patients were listed with higher allocation (inclusive of exception points) Model for End‐Stage Liver Disease scores (16 vs. 15, P < 0.01) and remained longer on the wait list (median 428 days vs. 187 days, P < 0.01). Conclusion: In this analysis of wait‐list candidates, we isolated 677 patients who declined an organ offer with a free‐text reason consistent with a “candidate‐related logistical reason.” Compared with non‐Hispanic Whites, Hispanics were at 1.44 odds of not accepting organ offers due to logistical reasons. These limited findings motivate further research into interventions that would improve candidates’ “readiness” to accept organ offers and may benefit racial/ethnic minorities on the liver‐transplantation wait list.

Effect of Season and Climate Regions on Liver Transplant Waitlist Outcomes

Shamaa, Mhd Tayseer MBBS; Kitajima, Toshihiro MD, PhD; Ivanics, Tommy MD; Shimada, Shingo MD, PhD; Mohamed, Adhnan MD; Rizzari, Michael D. MD; Collins, Kelly M. MD; Yoshida, Atsushi MD; Abouljoud, Marwan S. MD; Nagai, Shunji MD Author Information

Неселективные β-блокаторы при циррозе печени: эффект «терапевтического окна» и выживаемость пациентов

Objectives of the study: to analyze the survival rate of patients who received and did not receive various drugs of the class of non-selective beta-blockers (NSBB) while waiting for liver transplantation (LT) on the waiting list for liver transplantation (WLLT), depending on the presence or absence of a "therapeutic window" for the appointment of NSBB; to determine risk factors for death when prescribing various representatives of the NSBB class in patients with refractory ascites (RA). Material and methods. The retrospective case-control study was conducted. The "case" group included 278 adult patients with decompensated liver diseases of various etiologies included in the WLLT, who were treated with NSBB while waiting for LT. The "control" group consisted of 72 patients with decompensated liver diseases of various etiologies included in the WLLT, who did not receive NSBB therapy during the waiting period for LT. For the subsequent analysis, the group of patients receiving NSBB (n = 278) was divided into two subgroups: with the presence of a "therapeutic window" (n = 175), and without it (n = 103). The survival rate of patients was determined by the Kaplan - Mayer method. Predictors of mortality of patients receiving NSBB in the absence of a" therapeutic window "for NSBB were determined using the Cox proportional hazards model in the groups of patients with RA (n = 103) and non-RA (n = 175). Results. The survival rate of patients receiving NSBB in the presence of a" therapeutic window "for NSBB is significantly higher than in the group of patients receiving NSBB in WLLP while waiting for LT in the absence of a" therapeutic window " for NSBB (Log-Rank &lt; 0.0001). The risk of death in patients with RA treated with NSBB was significantly higher than in patients with non-RA (HR = 2.285; CI 1.237 4.220; p = 0.008). The risk of death for patients treated with propranol was significantly different from carvedilol (HR = 2,152 and HR = 0.765; p = 0.042, respectively). Conclusion. The results of the study confirmed the hypothesis that there is a "therapeutic window" for NSBB when they are prescribed to patients with decompensated cirrhosis of the liver and included in the WLLP. The use of NSBB contributes to an increase in the mortality of patients with RA, regardless of the type of drug, in the case when the "closed therapeutic window" phase develops. In order to reduce the mortality of patients waiting for LT for several years due to acute organ deficiency, doctors who lead patients to WLLT should assess the risk and benefit of using NSBB

S1074 Evaluating Immediate Outcomes of Liver Transplantation With HCV Positive Donor Grafts

Introduction: Currently, there is a shortage of available deceased donors to meet the demands of the liver transplant (LT) waitlist, resulting in a mortality rate of 12.3 per 100 waiting list years in 20191. The advent of safe, effective treatment for hepatitis C virus (HCV) has permitted use of HCV infected grafts for LT. Here we performed a descriptive analysis comparing immediate transplant related outcomes in patients who received an HCV+ graft and those who did not. Methods: This is a single center prospective cohort study of patients listed for OLT from April 2018 - June 2020. We compared immediate transplant outcomes of (1) patients willing vs. unwilling to receive an HCV+ graft and (2) recipients of HCV+ liver (antibody or nucleic acid testing [NAT] positive) vs. all other LT recipients. Stata v14.0 software was used for descriptive statistics using Chi-squared testing for categorical variables and Kruskal-Wallis test for continuous variables. Results: 146 patients were enrolled in the study of which 111 underwent LT. 86 were willing to accept an HCV+ graft and 25 declined. 15 patients received a HCV+ graft, of which 10 were NAT positive. Among those willing to receive an HCV+ liver, there was no significant difference in patient or donor age. There was a trend toward decreased transplant wait time for patients willing to accept HCV+ livers (171 vs. 237 days; p=0.07). Patients who received an HCV+ graft had significantly shorter cold ischemic time (351 vs. 426 minutes, p=0.01) and a shorter hospital length of stay after LT (10 vs. 15 days, p=0.02). Between HCV+ vs HCV- liver recipients, there was no difference in recipient age, donor age, time to transplant, warm ischemic time, need for reoperation, post transplant diabetes, or place of disposition following LT. Conclusion: Our data demonstrates that patients who received an HCV+ graft had a shorter cold ischemic time and hospital length of stay after LT. The difference in cold ischemic time likely reflects the use of donors more local to the LT center. A shorter ischemic time might confer improved immediate allograft function which might explain the reduced hospitalization amongst our HCV+ liver recipient patients. The shorter length of stay after LT likely reflects patient selection and use of HCV+ organs in those with lower MELD score. Further work is needed to understand long-term outcomes following use of HCV+ grafts.