Portable hypothermic oxygenated machine perfusion for organ preservation in liver transplantation: A randomized, open-label, clinical trial.

BACKGROUND AND AIMS: In liver transplantation, cold preservation induces ischemia, resulting in significant reperfusion injury. Hypothermic oxygenated machine perfusion (HMP-O 2 ) has shown benefits compared to static cold storage (SCS) by limiting ischemia-reperfusion injury. This study reports outcomes using a novel portable HMP-O 2 device in the first US randomized control trial. APPROACH AND RESULTS: The PILOT trial (NCT03484455) was a multicenter, randomized, open-label, noninferiority trial, with participants randomized to HMP-O 2 or SCS. HMP-O 2 livers were preserved using the Lifeport Liver Transporter and Vasosol perfusion solution. The primary outcome was early allograft dysfunction. Noninferiority margin was 7.5%. From April 3, 2019, to July 12, 2022, 179 patients were randomized to HMP-O 2 (n=90) or SCS (n=89). The per-protocol cohort included 63 HMP-O 2 and 73 SCS. Early allograft dysfunction occurred in 11.1% HMP-O 2 (N=7) and 16.4% SCS (N=12). The risk difference between HMP-O 2 and SCS was -5.33% (one-sided 95% upper confidence limit of 5.81%), establishing noninferiority. The risk of graft failure as predicted by Liver Graft Assessment Following Transplant score at seven days (L-GrAFT 7 ) was lower with HMP-O 2 [median (IQR) 3.4% (2.4-6.5) vs. 4.5% (2.9-9.4), p =0.024]. Primary nonfunction occurred in 2.2% of all SCS (n=3, p =0.10). Biliary strictures occurred in 16.4% SCS (n=12) and 6.3% (n=4) HMP-O 2 ( p =0.18). Nonanastomotic biliary strictures occurred only in SCS (n=4). CONCLUSIONS: HMP-O 2 demonstrates safety and noninferior efficacy for liver graft preservation in comparison to SCS. Early allograft failure by L-GrAFT 7 was lower in HMP-O 2 , suggesting improved early clinical function. Recipients of HMP-O 2 livers also demonstrated a lower incidence of primary nonfunction and biliary strictures, although this difference did not reach significance.

A modified liver donor risk index for pediatric liver transplant recipients.

The liver donor risk index (LDRI) was developed by Feng et al to predict the quality of donor liver allografts. However, there is currently no literature documenting the application and efficacy of Feng's LDRI specifically for the pediatric population. The goal of our study is to apply Feng's LDRI to our study population as well as develop a pediatric-specific LDRI. De-identified data from the United Network for Organ Sharing for 7836 recipients with pediatric transplant were retrospectively analyzed from January 1, 2000, to July 1, 2022. We performed a univariate and multivariate Cox regression analysis to determine the significant recipient and transplant factors impacting pediatric liver allograft survival. These significant factors were used to construct the pediatric-specific LDRI index. Receiver operator characteristic curve analysis was utilized to compare the pediatric-specific and Feng LDRI indexes at 1, 5, and 10 years.​​ Our pediatric-specific LDRI includes 4 variables found to be significant in pediatric populations: donor age: 35-50, ≥ 50; cold ischemia time ≤ 6, and aspartate aminotransferase level > 1000. In addition, our pediatric-specific LDRI had a higher receiver operator characteristic c -statistic compared to Feng's LDRI at 1 year (0.57 vs. 0.55), 5 years (0.57 vs. 0.50), and 10 years (0.58 vs. 0.47). Our findings indicate that there is a need to create a pediatric-specific LDRI as the Feng LDRI has not been shown to be efficacious in pediatric populations. Our index may serve as a starting point for the development of a comprehensive pediatric LDRI.

Risk Index Predicts Pediatric Heart Allograft Non-Utilization.

BACKGROUND: Children listed for heart transplantation face the highest waitlist mortality among all solid organ transplant patients (14%). Attempts at decreasing donor allograft non-utilization (41.5%) could potentially decrease waitlist mortality for pediatric heart transplant patients. Our aim was to quantify the non-utilization risk of pediatric donor heart allografts at the time of initial offering. METHODS: Using the United Network of Organ Sharing (UNOS) database, we retrospectively analyzed 8823 deceased donors (≤18 years old) data through univariable and multivariable analysis and logistic regression models. These factors were divided into a training (n = 5882) and validation set (n = 2941). Donor clinical characteristics and laboratory values were used to predict non-utilization of donor hearts. The multivariable analysis used factors that were significant from the univariable analysis (p-value < .05), and the pediatric non-utilization risk index (pDRSI) included significant factors from the multivariable analysis, producing an overall risk score for non-utilization. With these data, we created a non-utilization risk index to predict likelihood of donor allograft non-utilization. RESULTS: From the 24 potential factors that were identified from univariable analysis, 17 were significant predictors (p < .05) of pediatric heart non-utilization in the multivariable analysis. Low left ventricular ejection fraction (odds ratio (OR)-35.3), hepatitis C positive donor (OR-23.3), high left ventricular ejection fraction (OR-3.29), and hepatitis B positive donor (OR-3.27) were the most significant risk factors. The phDSRI has a C-statistic of 0.80 for the training set and 0.80 for the validation set. CONCLUSION: Using over 8000 donors, the phDSRI uses 17 significant risk factors to predict risk of pediatric heart donor allograft non-utilization.

Constructing an Intent-to-Treat Score Index to Predict Survival Outcomes in Pediatric Liver Transplant Recipients.

BACKGROUND: Waitlist and posttransplant outcomes have been widely reported for pediatric liver transplantation. Yet, analyzing these metrics individually fails to provide a holistic perspective for patients and their families. Intent-to-treat (ITT) analysis fills this gap by studying the associations between waitlist outcomes, organ availability, and posttransplant outcomes. Our study aimed to construct a predictive index utilizing ITT analysis for pediatric liver transplant recipients (Pedi-ITT). METHODS: We performed a retrospective analysis utilizing de-identified data provided by the United Network for Organ Sharing (UNOS) from March 1, 2002, to December 31, 2021. We analyzed data for 12 926 pediatric recipients (age <18). We conducted a univariate and multivariable logistic regression to find the significant predictive factors affecting ITT survival. A scoring index was constructed to stratify outcome risk on the basis of the significant factors identified by regression analysis. RESULTS: Multivariable analysis found the following factors to be significantly associated with death on the waitlist or after transplant: gender, diagnosis, UNOS region, ascites, diabetes mellitus, age at the time of listing, serum sodium at the time of listing, total bilirubin at the time of listing, serum creatinine at the time of listing, INR at the time of listing, history of ventilator use, and history of re-transplantation. Using receiver operator characteristic analysis, the Pedi-ITT index had a c-statistic of 0.79 (95% confidence interval [CI]: 0.76-0.82). The c-statistics of the Model for End-Stage Liver Disease/Pediatric for End-Stage Liver Disease and pediatric version of the Survival Outcomes Following Liver Transplantation score indices were 0.74 (CI: 0.71-0.76) and 0.69 (CI: 0.66-0.72), respectively. CONCLUSIONS: The Pedi-ITT index provides an additional prognostic model with moderate predictive power to assess outcomes associated with pediatric liver transplantation. Further analysis should focus on increasing the predictive power of the index.

Estimating risk of prolonged mechanical ventilation after liver transplantation in children: PROVE-ALT score.

BACKGROUND: Children at high risk for prolonged mechanical ventilation (PMV) after liver transplantation (LT) need to be identified early to optimize pulmonary support, allocate resources, and improve surgical outcomes. We aimed to develop and validate a metric that can estimate risk for Prolonged Ventilation After LT (PROVE-ALT). METHODS: We identified preoperative risk factors for PMV by univariable analysis in a retrospective cohort of pediatric LT recipients between 2011 and 2017 (n = 205; derivation cohort). We created the PROVE-ALT score by mapping multivariable logistic regression coefficients as integers, with cutoff values using the Youden Index. We validated the score by C-statistic in a retrospectively collected separate cohort of pediatric LT recipients between 2018 and 2021 (n = 133, validation cohort). RESULTS: Among total 338 patients, 21% (n = 72) were infants; 49% (n = 167) had cirrhosis; 8% (n = 27) required continuous renal replacement therapy (CRRT); and 32% (n = 111) required management in hospital (MIH) before LT. Incidence of PMV post-LT was 20% (n = 69) and 3% (n = 12) required tracheostomy. Independent risk factors (OR [95% CI]) for PMV were cirrhosis (3.8 [1-14], p = .04); age <1-year (8.2 [2-30], p = .001); need for preoperative CRRT (6.3 [1.2-32], p = .02); and MIH before LT (12.4 [2.1-71], p = .004). PROVE-ALT score ≥8 [Range = 0-21] accurately predicted PMV in the validation cohort with 73% sensitivity and 80% specificity (AUC: 0.81; 95% CI: 0.71-0.91). CONCLUSION: PROVE-ALT can predict PMV after pediatric LT with a high degree of sensitivity and specificity. Once externally validated in other centers, PROVE-ALT will empower clinicians to plan patient-specific ventilation strategies, provide parental anticipatory guidance, and optimize hospital resources.

Predicting wait time for pediatric kidney transplant: a novel index.

BACKGROUND: Over one thousand pediatric kidney transplant candidates are added to the waitlist annually, yet the prospective time spent waiting is unknown for many. Our study fills this gap by identifying variables that impact waitlist time and by creating an index to predict the likelihood of a pediatric candidate receiving a transplant within 1 year of listing. This index could be used to guide patient management by giving clinicians a potential timeline for each candidate's listing based on a unique combination of risk factors. METHODS: A retrospective analysis of 3757 pediatric kidney transplant candidates from the 2014 to 2020 OPTN/UNOS database was performed. The data was randomly divided into a training set, comprising two-thirds of the data, and a testing set, comprising one-third of the data. From the training set, univariable and multivariable logistic regressions were used to identify significant predictive factors affecting wait times. A predictive index was created using variables significant in the multivariable analysis. The index's ability to predict likelihood of transplantation within 1 year of listing was validated using ROC analysis on the training set. Validation of the index using ROC analysis was repeated on the testing set. RESULTS: A total of 10 variables were found to be significant. The five most significant variables include the following: blood group, B (OR 0.65); dialysis status (OR 3.67); kidney disease etiology, SLE (OR 0.38); and OPTN region, 5 (OR 0.54) and 6 (OR 0.46). ROC analysis of the index on the training set yielded a c-statistic of 0.71. ROC analysis of the index on the testing set yielded a c-statistic of 0.68. CONCLUSIONS: This index is a modest prognostic model to assess time to pediatric kidney transplantation. It is intended as a supplementary tool to guide patient management by providing clinicians with an individualized prospective timeline for each candidate. Early identification of candidates with potential for prolonged waiting times may help encourage more living donation including paired donation chains.

Improved Survival After Liver Transplantation for Patients With Human Immunodeficiency Virus (HIV) and HIV/Hepatitis C Virus Coinfection in the Integrase Strand Transfer Inhibitor and Direct-Acting Antiviral Eras.

BACKGROUND: People with human immunodeficiency virus (HIV) with and without hepatitis C virus (HCV) coinfection had poor outcomes after liver transplant (LT). Integrase strand transfer inhibitors (INSTIs) and direct-acting antivirals (DAAs) have changed the treatment landscape for HIV and HCV, respectively, but their impact on LT outcomes remains unclear. METHODS: This retrospective analysis of adults with HIV monoinfection (n = 246) and HIV/HCV coinfection (n = 286) who received LT compared mortality in patients with HIV who received LT before versus after approval of INSTIs and in patients with HIV/HCV coinfection who received LT before versus after approval of DAAs. In secondary analysis, we compared the outcomes in the different eras with those of propensity score-matched control cohorts of LT recipients without HIV or HCV infection. RESULTS: LT recipients with HIV monoinfection did not experience a significant improvement in survival between the pre-INSTI and INSTI recipients with HIV (adjusted hazard ratio [aHR], 0.70 [95% confidence interval {CI}, .36-1.34]). However, recipients with HIV/HCV coinfection in the DAA era had a 47% reduction (aHR, 0.53 [95% CI, .31-9.2] in 1-year mortality compared with coinfected recipients in the pre-DAA era. Compared to recipients without HIV or HCV, HIV-monoinfected recipients had higher mortality during the pre-INSTI era, but survival was comparable between groups during the INSTI era. HIV/HCV-coinfected recipients also experienced comparable survival during the DAA era compared to recipients without HCV or HIV. CONCLUSIONS: Post-LT survival for people with HIV monoinfection and HIV/HCV coinfection has improved with the introduction of INSTI and DAA therapy, suggesting that LT has become safer in these populations.

Reduction in Racial and Ethnic Disparity in Survival Following Liver Transplant for Hepatocellular Carcinoma in the Direct-acting Antiviral Era.

BACKGROUND & AIMS: Black patients with hepatocellular cancer (HCC), often attributed to hepatitis C virus (HCV) infection, have suboptimal survival following liver transplant (LT). We evaluated the impact of direct-acting antiviral (DAA) availability on racial and ethnic disparities in wait list burden post-LT survival for candidates with HCC. METHODS: Using the United Network for Organ Sharing registry, we identified patients with HCC who were listed and/or underwent LT from 2009 to 2020. Based on date of LT, patients were categorized into 2 era-based cohorts: the pre-DAA era (LT between 2009 and 2011) and DAA era (LT between 2015 and 2017, with follow-up through 2020). Kaplan-Meier and Cox proportional hazards analyses were used to compare post-LT survival, stratified by era and race and ethnicity. RESULTS: Annual wait list additions for HCV-related HCC decreased significantly in White and Hispanic patients during the DAA era, with no change (P = .14) in Black patients. Black patients had lower 3-year survival than White patients in the pre-DAA era (70.6% vs 80.1%, respectively; P < .001) but comparable survival in the DAA era (82.1% vs 85.5%, respectively; P = .16). 0n multivariable analysis, Black patients in the pre-DAA era had a 53% higher risk (adjusted hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.28-1.84), for mortality than White patients, but mortality was comparable in the DAA era (adjusted HR, 1.23; 95% CI, 0.99-1.52). In a stratified analysis in Black patients, HCV-related HCC carried more than a 2-fold higher risk of mortality in the pre-DAA era (adjusted HR, 2.86; 95% CI, 1.50-5.43), which was reduced in the DAA era (adjusted HR, 1.34; 95% CI, 0.78-2.30). CONCLUSIONS: With the availability of DAA therapy, racial disparities in post-LT survival have improved.

Cost of Care for Patients With Cirrhosis.

INTRODUCTION: There are limited longitudinal data on the cost of treating patients with cirrhosis, which hampers value-based improvement initiatives. METHODS: We conducted a retrospective cohort study of patients with cirrhosis seen in the Veterans Affairs health care system from 2011 to 2015. Patients were followed up through 2019. We identified a sex-matched and age-matched control cohort without cirrhosis. We estimated incremental annual health care costs attributable to cirrhosis for 4 years overall and in subgroups based on severity (compensated, decompensated), cirrhosis complications (ascites, encephalopathy, varices, hepatocellular cancer, acute kidney injury), and comorbidity (Deyo index). RESULTS: We compared 39,361 patients with cirrhosis with 138,964 controls. The incremental adjusted costs for caring of patients with cirrhosis were $35,029 (95% confidence interval $32,473-$37,585) during the first year and ranged from $14,216 to $17,629 in the subsequent 3 years. Cirrhosis complications accounted for most of these costs. Costs of managing patients with hepatic encephalopathy (year 1 cost, $50,080) or ascites ($50,364) were higher than the costs of managing patients with varices ($20,488) or hepatocellular cancer ($37,639) in the first year. Patients with acute kidney injury or those who had multimorbidity were the most costly at $64,413 and $66,653 in the first year, respectively. DISCUSSION: Patients with cirrhosis had substantially higher health care costs than matched controls and multimorbid patients had even higher costs. Cirrhosis complications accounted for most of the excess cost, so preventing complications has the largest potential for cost saving and could serve as targets for improvement.

Long-term outcomes and trends in liver transplantation for hereditary hemochromatosis in the United States.

There have been conflicting data regarding liver transplantation (LT) outcomes for hereditary hemochromatosis (HH), with no recent data on LT outcomes in patients with HH in the past decade. Using the United Network for Organ Sharing registry, we evaluated waitlist and post-LT survival in all adult patients listed for HH without concomitant liver disease from 2003 to 2019. Post-LT survival for HH was compared with a propensity-matched (recipient and donor factors) cohort of recipients with chronic liver disease (CLD). From 2003 to 2019, 862 patients with HH were listed for LT, of which 55.6% ( n = 479) patients underwent LT. The 1- and 5-year post-LT survival rates in patients with HH were 88.7% (95% confidence interval [CI], 85.4%-91.4%) and 77.5% (95% CI, 72.8%-81.4%), respectively, and were comparable with those in the propensity-matched CLD cohort ( p value = 0.96). Post-LT survival for HH was lower than for Wilson's disease, another hereditary metabolic liver disease with similar LT volume ( n = 365). Predictors for long-term (5-year) post-LT mortality included presence of portal vein thrombosis (hazard ratio [HR], 1.96; 95% CI, 1.07-3.58), obesity measurements greater than Class II (HR, 1.98; 95% CI, 1.16-3.39), and Karnofsky performance status (HR, 0.98; 95% CI, 0.97-0.99) at the time of LT. The leading cause of post-LT death ( n = 145) was malignancy (25.5%), whereas cardiac disease was the cause in less than 10% of recipients. In conclusion, short- and long-term survival rates for HH are excellent and comparable with those of other LT recipients. Improving extrahepatic metabolic factors and functional status in patients with HH prior to LT may improve outcomes.

Outcomes in liver transplant recipients with nonalcoholic fatty liver disease-related HCC: results from the US multicenter HCC transplant consortium.

NAFLD will soon be the most common indication for liver transplantation (LT). In NAFLD, HCC may occur at earlier stages of fibrosis and present with more advanced tumor stage, raising concern for aggressive disease. Thus, adult LT recipients with HCC from 20 US centers transplanted between 2002 and 2013 were analyzed to determine whether NAFLD impacts recurrence-free post-LT survival. Five hundred and thirty-eight (10.8%) of 4981 total patients had NAFLD. Patients with NAFLD were significantly older (63 vs. 58, p<0.001), had higher body mass index (30.5 vs. 27.4, p<0.001), and were more likely to have diabetes (57.3% vs. 28.8%, p<0.001). Patients with NAFLD were less likely to receive pre-LT locoregional therapy (63.6% vs. 72.9%, p<0.001), had higher median lab MELD (15 vs. 13, p<0.001) and neutrophil-lymphocyte ratio (3.8 vs. 2.9, p<0.001), and were more likely to have their maximum pre-LT alpha fetoprotein at time of LT (44.1% vs. 36.1%, p<0.001). NAFLD patients were more likely to have an incidental HCC on explant (19.4% vs. 10.4%, p<0.001); however, explant characteristics including tumor differentiation and vascular invasion were not different between groups. Comparing NAFLD and non-NAFLD patients, the 1, 3, and 5-year cumulative incidence of recurrence (3.1%, 9.1%, 11.5% vs. 4.9%, 10.1%, 12.6%, p=0.36) and recurrence-free survival rates (87%, 76%, and 67% vs. 87%, 75%, and 67%, p=0.97) were not different. In competing risks analysis, NAFLD did not significantly impact recurrence in univariable (HR: 0.88, p=0.36) nor in adjusted analysis (HR: 0.91, p=0.49). With NAFLD among the most common causes of HCC and poised to become the leading indication for LT, a better understanding of disease-specific models to predict recurrence is needed. In this NAFLD cohort, incidental HCCs were common, raising concerns about early detection. However, despite less locoregional therapy and high neutrophil-lymphocyte ratio, explant tumor characteristics and post-transplant recurrence-free survival were not different compared to non-NAFLD patients.

Development and validation of a REcurrent Liver cAncer Prediction ScorE (RELAPSE) following liver transplantation in patients with hepatocellular carcinoma: Analysis of the US Multicenter HCC Transplant Consortium.

HCC recurrence following liver transplantation (LT) is highly morbid and occurs despite strict patient selection criteria. Individualized prediction of post-LT HCC recurrence risk remains an important need. Clinico-radiologic and pathologic data of 4981 patients with HCC undergoing LT from the US Multicenter HCC Transplant Consortium (UMHTC) were analyzed to develop a REcurrent Liver cAncer Prediction ScorE (RELAPSE). Multivariable Fine and Gray competing risk analysis and machine learning algorithms (Random Survival Forest and Classification and Regression Tree models) identified variables to model HCC recurrence. RELAPSE was externally validated in 1160 HCC LT recipients from the European Hepatocellular Cancer Liver Transplant study group. Of 4981 UMHTC patients with HCC undergoing LT, 71.9% were within Milan criteria, 16.1% were initially beyond Milan criteria with 9.4% downstaged before LT, and 12.0% had incidental HCC on explant pathology. Overall and recurrence-free survival at 1, 3, and 5 years was 89.7%, 78.6%, and 69.8% and 86.8%, 74.9%, and 66.7%, respectively, with a 5-year incidence of HCC recurrence of 12.5% (median 16 months) and non-HCC mortality of 20.8%. A multivariable model identified maximum alpha-fetoprotein (HR = 1.35 per-log SD, 95% CI,1.22-1.50, p < 0.001), neutrophil-lymphocyte ratio (HR = 1.16 per-log SD, 95% CI,1.04-1.28, p < 0.006), pathologic maximum tumor diameter (HR = 1.53 per-log SD, 95% CI, 1.35-1.73, p < 0.001), microvascular (HR = 2.37, 95%-CI, 1.87-2.99, p < 0.001) and macrovascular (HR = 3.38, 95% CI, 2.41-4.75, p < 0.001) invasion, and tumor differentiation (moderate HR = 1.75, 95% CI, 1.29-2.37, p < 0.001; poor HR = 2.62, 95% CI, 1.54-3.32, p < 0.001) as independent variables predicting post-LT HCC recurrence (C-statistic = 0.78). Machine learning algorithms incorporating additional covariates improved prediction of recurrence (Random Survival Forest C-statistic = 0.81). Despite significant differences in European Hepatocellular Cancer Liver Transplant recipient radiologic, treatment, and pathologic characteristics, external validation of RELAPSE demonstrated consistent 2- and 5-year recurrence risk discrimination (AUCs 0.77 and 0.75, respectively). We developed and externally validated a RELAPSE score that accurately discriminates post-LT HCC recurrence risk and may allow for individualized post-LT surveillance, immunosuppression modification, and selection of high-risk patients for adjuvant therapies.

The utility of machine learning for predicting donor discard in abdominal transplantation.

BACKGROUND: Increasing access and better allocation of organs in the field of transplantation is a critical problem in clinical care. Limitations exist in accurately predicting allograft discard. Potential exists for machine learning to provide a balanced assessment of the potential for an organ to be used in a transplantation procedure. METHODS: We accessed and utilized all available deceased donor United Network for Organ Sharing data from 1987 to 2020. With these data, we evaluated the performance of multiple machine learning methods for predicting organ use. The machine learning methods trialed included XGBoost, random forest, Naïve Bayes (NB), logistic regression, and fully connected feedforward neural network classifier methods. The top two methods, XGBoost and random forest, were fully developed using 10-fold cross-validation and Bayesian optimization of hyperparameters. RESULTS: The top performing model at predicting liver organ use was an XGBoost model which achieved an AUC-ROC of .925, an AUC-PR of .868, and an F1 statistic of .756. The top performing model for predicting kidney organ use classification was an XGBoost model which achieved an AUC-ROC of .952, and AUC-PR of .883, and an F1 statistic of .786. CONCLUSIONS: The XGBoost method demonstrated a significant improvement in predicting donor allograft discard for both kidney and livers in solid organ transplantation procedures. Machine learning methods are well suited to be incorporated into the clinical workflow; they can provide robust quantitative predictions and meaningful data insights for clinician consideration and transplantation decision-making.

A novel risk score for predicting prolonged length of stay following pediatric kidney transplant.

BACKGROUND: Kidney transplants (KT) are accepted as the kidney replacement therapy of choice for children with kidney failure. The surgery itself may be more difficult especially in small children, and often leads to significant hospital stays. There is little research on predicting prolonged length of stay (LOS) in children. We aim to examine the factors associated with prolonged LOS following pediatric KT to help clinicians make informed decisions, better counsel families, and potentially reduce preventable causes of prolonged stay. METHODS: We retrospectively analyzed the United Network for Organ Sharing database for all KT recipients less than 18 years old between January 2014 and July 2022 (n = 3693). Donor and recipient factors were tested in univariate and multivariate logistic analysis using stepwise elimination of non-significant factors to create a final regression model predicting LOS longer than 14 days. Values were assigned to significant factors to create risk scores for each individual patient. RESULTS: In the final model, only primary diagnosis of focal segmental glomerulosclerosis, dialysis prior to KT, geographic region, and recipient weight prior to KT were significant predictors of LOS longer than 14 days. The C-statistic of the model is 0.7308. The C-statistic of the risk score is 0.7221. CONCLUSIONS: Knowledge of the risk factors affecting prolonged LOS following pediatric KT can help identify patients at risk of increased resource use and potential hospital-acquired complications. Using our index, we identified some of these specific risk factors and created a risk score that can stratify pediatric recipients into low, medium, or high risk groups. A higher resolution version of the Graphical abstract is available as Supplementary information.

A modified Kidney Donor Risk Index for pediatric kidney transplant recipients.

BACKGROUND: The Kidney Donor Risk Index (KDRI) by Rao et al. was developed to measure the quality of kidney allografts. While Rao's KDRI has been found to be a robust measure of kidney allograft survival for adult kidney transplant recipients, many studies have indicated the need to create a distinct pediatric KDRI. METHODS: Our retrospective study utilized data from the United Network for Organ Sharing database. We examined 9295 deceased donor recipients' data for age < 18 years from 1990 to 2020. We performed a multivariate Cox regression to determine the significant recipient and transplant factors impacting pediatric kidney allograft survival. RESULTS: Multivariate analysis found 5 donor factors to be independently associated with graft failure or recipient death: age, female sex, anoxia as the cause of death, history of cigarette use, and cold ischemia time. Using receiver operator characteristic (ROC) curve analysis and analyzing the predictive value of each KDRI at 1, 5, and 10 years, the proposed pediatric KDRI had a statistically significant and higher predictive value for pediatric recipients at 5 (0.60 versus 0.57) and 10 years (0.61 versus 0.57) than the Rao KDRI. CONCLUSIONS: The proposed pediatric KDRI may provide a more accurate and simpler index to assess the quality of kidney allografts for pediatric recipients. However, due to the mild increase in predictive capabilities over the Rao index, the study serves as a proof of concept to develop a pediatric KDRI. Further studies should focus on increasing the index's predictive capabilities. A higher resolution version of the Graphical abstract is available as Supplementary information.

Survival Benefit of Solid-Organ Transplantation: 10-Year Update.

IMPORTANCE: Transplantation has transformed into a burgeoning field that is rapidly evolving to optimize organ distribution and survival outcomes. The years since 2012 (the last comprehensive study) have seen changes in transplantation, such as advances in immunotherapy and novel indices, that necessitate an updated analysis of survival benefit. DESIGN: Our goal was to determine the survival benefit for solid-organ transplants in the United Network for Organ Sharing (UNOS) database for a three decade period and provide updates on advancements since 2012. Our retrospective analysis examined data containing U.S. patient records from September 1, 1987, to September 1, 2021. RESULTS: We found that 3,430,272 life-years were saved over our transplant period (4.33 life-years saved per patient); kidney-1,998,492 life-years; liver -767,414; heart-435,312; lung-116,625; pancreas-kidney-123,463; pancreas-30,575; intestine-7901. After matching, 3,296,851 life-years were saved. Life-years saved and median survival increased for all organs between 2012 and 2021. Compared to 2012, median survival increased in kidney (from 12.4 to 14.76 years), liver (from 11.6 to 14.59), heart (9.5 to 11.73), lung (5.2 to 5.63), pancreas-kidney (from 14.5 to 16.88), pancreas (from 13.3 to 16.10). When compared to 2012, the percent transplanted increased in kidney, liver, heart, lung, and intestine, while pancreas-kidney and pancreas show decreased percent transplanted. CONCLUSION: Our study underscores the tremendous survival benefits of solid organ transplantation (over 3.4 million life-years saved) and shows improvements since 2012. Our study also highlights areas of transplantation, notably pancreas transplants, that may necessitate reinvigorated attention.

Clinical Course and Outcomes of Patients with Nonalcoholic Fatty Liver Disease-Related Hepatocellular Cancer (NAFLD-HCC).

BACKGROUND & AIMS: Among etiologies for hepatocellular (HCC), nonalcoholic fatty liver disease (NAFLD) carries a high risk of competing non-cancer mortality. The effect of cancer and non-cancer factors on risk of death after NAFLD-HCC diagnosis remains unclear. We aimed to evaluate the role of non-cancer mortality with NAFLD-HCC. METHODS: Using a retrospective cohort of patients with NAFLD diagnosed at 130 facilities in the Veterans Administration, we identified patients with incident HCC diagnosed between January 1, 2005 and June 30, 2018. We determined cause of death as HCC-related, non-HCC liver-related, and non-liver-related after HCC diagnosis. We used Cox proportional hazards regression models to evaluate the effect of clinical factors on cause-specific mortality after NAFLD-HCC diagnosis. RESULTS: We identified 776 patients with incident HCC. Mean age at HCC diagnosis was 70.1 year, 22.2% had Barcelona Clinic Liver Cancer (BCLC) stage 0-A, and 67.0% had more than one comorbidity. 1- and 3-year mortality rates were 47.0% and 69.6%, respectively. Most deaths (72.2% at 3 years) were attributable to HCC. In HCC patients who received curative treatment, non-cancer mortality accounted for 40% of all deaths between 3 and 5 years after treatment. Poor performance status (ECOG 3/4, HR 5.03, 95% CI: 2.59-9.77) and older age (65-75, HR 1.94, 95% CI: 1.06-3.54) were strongly associated with non-cancer mortality. CONCLUSION: Although most patients with NAFLD-HCC die of HCC, non-cancer mortality represents a clinically meaningful competing event for patients receiving curative treatment, underscoring the importance of assessing and managing risk factors of non-cancer morbidity and mortality. TRIAL AND REGISTRATION: N/A.

Low-dose aspirin confers protection against acute cellular allograft rejection after primary liver transplantation.

This study investigated the effect of low-dose aspirin in primary adult liver transplantation (LT) on acute cellular rejection (ACR) as well as arterial patency rates. The use of low-dose aspirin after LT is practiced by many transplant centers to minimize the risk of hepatic artery thrombosis (HAT), although solid recommendations do not exist. However, aspirin also possesses potent anti-inflammatory properties and might mitigate inflammatory processes after LT, such as rejection. Therefore, we hypothesized that the use of aspirin after LT has a protective effect against ACR. This is an international, multicenter cohort study of primary adult deceased donor LT. The study included 17 high-volume LT centers and covered the 3-year period from 2013 to 2015 to allow a minimum 5-year follow-up. In this cohort of 2365 patients, prophylactic antiplatelet therapy with low-dose aspirin was administered in 1436 recipients (61%). The 1-year rejection-free survival rate was 89% in the aspirin group versus 82% in the no-aspirin group (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.63-0.94; p = 0.01). The 1-year primary arterial patency rates were 99% in the aspirin group and 96% in the no-aspirin group with an HR of 0.23 (95% CI, 0.13-0.40; p < 0.001). Low-dose aspirin was associated with a lower risk of ACR and HAT after LT, especially in the first vulnerable year after transplantation. Therefore, low-dose aspirin use after primary LT should be evaluated to protect the liver graft from ACR and to maintain arterial patency.

Impact of COVID-19 Pandemic on Liver Transplantation and Alcohol-Associated Liver Disease in the USA.

BACKGROUND AND AIMS: The surge in unhealthy alcohol use during the COVID-19 pandemic may have detrimental effects on the rising burden of alcohol-associated liver disease (ALD) on liver transplantation (LT) in the USA. We evaluated the effect of the pandemic on temporal trends for LT including ALD. APPROACH AND RESULTS: Using data from United Network for Organ Sharing, we analyzed wait-list outcomes in the USA through March 1, 2021. In a short-period analysis, patients listed or transplanted between June 1, 2019, and February 29, 2020, were defined as the "pre-COVID" era, and after April 1, 2020, were defined as the "COVID" era. Interrupted time-series analyses using monthly count data from 2016-2020 were constructed to evaluate the rate change for listing and LT before and during the COVID-19 pandemic. Rates for listings (P = 0.19) and LT (P = 0.14) were unchanged during the pandemic despite a significant reduction in the monthly listing rates for HCV (-21.69%, P < 0.001) and NASH (-13.18%; P < 0.001). There was a significant increase in ALD listing (+7.26%; P < 0.001) and LT (10.67%; P < 0.001) during the pandemic. In the COVID era, ALD (40.1%) accounted for more listings than those due to HCV (12.4%) and NASH (23.4%) combined. The greatest increase in ALD occurred in young adults (+33%) and patients with severe alcohol-associated hepatitis (+50%). Patients with ALD presented with a higher acuity of illness, with 30.8% of listings and 44.8% of LT having a Model for End-Stage Liver Disease-Sodium score ≥30. CONCLUSIONS: Since the start of COVID-19 pandemic, ALD has become the most common indication for listing and the fastest increasing cause for LT. Collective efforts are urgently needed to stem the rising tide of ALD on health care resources.

Trends in marginal lung allograft survival: Advanced-age donors improve.

INTRODUCTION: Although lung demand continues to outpace supply, 75% of potential donor lungs are discarded without being transplanted in the United States. To identify the discarded cohorts best suited to alleviate the lung shortage and reduce waitlist mortality, we explored changes in survival over time for five marginal donor definitions: age >60 years, smoking history >20 pack-years, PaO2 /FiO2  < 300 mmHg, purulent bronchoscopic secretions, and chest radiograph infiltrates. METHODS: Our retrospective cohort study separated 27 803 lung recipients in the UNOS Database into three 5-year eras by transplant date: 2005-2009, 2010-2014, and 2015-2019. Multivariable Cox proportional hazards regression and Kaplan-Meier analysis with log-rank test were used to compare survival across the eras. RESULTS: Three definitions-low PaO2 /FiO2 , purulent bronchoscopic secretions, and abnormal chest radiographs-did not bear out as truly marginal, demonstrating lack of significantly elevated risk. Advanced donor age demonstrated considerable survival improvement (HR (95% CI): 1.47 (1.26-1.72) in 2005-2009 down to 1.14 (.97-1.35) for 2015-2019), with protective factors being recipients <60 years, moderate recipient BMI, and low Lung Allocation Score (LAS). Donors with smoking history failed to demonstrate any significant improvement (HR (95% CI): 1.09 (1.01-1.17) in 2005-2009 increasing to 1.22 (1.08-1.38) in 2015-2019). CONCLUSIONS: Advanced donor age, previously the most significant risk factor, has improved to near-benchmark levels, demonstrating the possibility for matching older donors to healthier non-elderly recipients in selected circumstances. Low PaO2 /FiO2 , bronchoscopic secretions, and abnormal radiographs demonstrated survival on par with standard donors. Significant donor smoking history, a moderate risk factor, has failed to improve.