Post-transplant outcomes and financial burden of donation after circulatory death donor liver transplant after the implementation of acuity circle policy.

BACKGROUND: After implementation of the Acuity Circles (AC) allocation policy, use of DCD liver grafts has increased in the United States. METHODS: We evaluated the impact of AC on rates of DCD-liver transplants (LT), their outcomes, and medical costs in a single practice. Adult LT patients were classified into three eras: Era 1 (pre-AC, 1/01/2015-12/31/2017); Era 2 (late pre-AC era, 1/01/2018-02/03/2020); and Era 3 (AC era, 05/10/2020-09/30/2021). RESULTS: A total of 520 eligible LTs were performed; 87 were DCD, and 433 were DBD. With each successive era, the proportion of DCD increased (Era 1: 11%; Era 2: 20%; Era 3: 24%; p < .001). DCD recipients had longer ICU stays, higher re-admission/re-operation rates, and higher incidence of ischemic cholangiopathy compared to those with DBD. Direct, surgical, and ICU costs during first admission were higher with DCD than DBD (+8.0%, p < .001; +4.2%, p < .001; and +33.3%, p = .001). DCD-related costs increased after Era 1 (Direct: +4.9% [Era 2 vs. 1] and +12.4% [Era 3 vs. 1], p = .04; Surgical: +17.7% and +21.7%, p < .001). In the AC era, there was a significantly higher proportion of donors ≥50 years, and more national organ sharing. Compared to DCD from donors <50 years, DCD from donors ≥50 years was associated with significantly higher total direct, surgical, and ICU costs (+12.6%, p = .01; +9.5%, p = .01; +84.6%, p = .03). CONCLUSIONS: The proportion of DCD-LT, especially from older donors, has increased after the implementation of AC policies. These changes are likely to be associated with higher costs in the AC era.

Effects of the implementation of acuity circle policy on waitlist and post-transplant outcomes of liver re-transplantation.

BACKGROUND: Acuity circle (AC) policy implementation improved the waitlist outcomes for certain liver transplant (LT)-candidates. The impact of the policy implementation for liver retransplant (reLT) candidates is unknown. METHODS: Using Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) data from January, 2018 to September, 2021, we investigated the effect of the AC policy on waitlist and post-LT outcomes among patients who had previously received a LT. Patients were categorized by relisting date: Pre-AC (Era 1: January 1, 2018-February 3, 2020; n = 750); and Post-AC (Era 2: February 4, 2020-June 30, 2021; n = 556). Patient and donor characteristics, as well as on-waitlist and post-reLT outcomes were compared across eras. RESULTS: In Era 2, the probability of transplant within 90 days overall and among patients relisted > 14 days from initial transplant (late relisting) were significantly higher compared to Era 1 (subdistribution hazard ratio [sHR] 1.40, 95% CI 1.18-1.64, p < .001; sHR 1.52, 95% CI 1.23-1.88, p = .001, respectively). However, there was no difference by era among patients relisted ≤14 days from initial transplant (early relisting; sHR 1.21, 95% CI .93-1.57, p = .15). Likewise, among early relisting patients, risks for 180-day graft loss and mortality were significantly higher in Era 2 versus Era 1 (adjusted hazard ratio [aHR] 5.77, 95% CI 1.71-19.51, p = .004; and aHR 8.22, 95% CI 1.85-36.59, p = .005, respectively); for late relisting patients, risks for these outcomes were similar across eras. CONCLUSION: Our results show that the implementation of AC policy has improved transplant rates and reduced waiting time for reLT candidates listed > 14 days from initial transplant. However, the impact upon early relisting patients may be mixed.

The molecular phenotypes of injury, steatohepatitis, and fibrosis in liver transplant biopsies in the INTERLIVER study.

To extend previous molecular analyses of rejection in liver transplant biopsies in the INTERLIVER study (ClinicalTrials.gov #NCT03193151), the present study aimed to define the gene expression selective for parenchymal injury, fibrosis, and steatohepatitis. We analyzed genome-wide microarray measurements from 337 liver transplant biopsies from 13 centers. We examined expression of genes previously annotated as increased in injury and fibrosis using principal component analysis (PCA). PC1 reflected parenchymal injury and related inflammation in the early posttransplant period, slowly regressing over many months. PC2 separated early injury from late fibrosis. Positive PC3 identified a distinct mildly inflamed state correlating with histologic steatohepatitis. Injury PCs correlated with liver function and histologic abnormalities. A classifier trained on histologic steatohepatitis predicted histologic steatohepatitis with cross-validated AUC = 0.83, and was associated with pathways reflecting metabolic abnormalities distinct from fibrosis. PC2 predicted histologic fibrosis (AUC = 0.80), as did a molecular fibrosis classifier (AUC = 0.74). The fibrosis classifier correlated with matrix remodeling pathways with minimal overlap with those selective for steatohepatitis, although some biopsies had both. Genome-wide assessment of liver transplant biopsies can not only detect molecular changes induced by rejection but also those correlating with parenchymal injury, steatohepatitis, and fibrosis, offering potential insights into disease mechanisms for primary diseases.

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 90 days 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.

Liver Transplant Recipient Characteristics Associated With Worse Post-Transplant Outcomes in Using Elderly Donors.

Advanced age of liver donor is a risk factor for graft loss after transplant. We sought to identify recipient characteristics associated with negative post-liver transplant (LT) outcomes in the context of elderly donors. Using 2014-2019 OPTN/UNOS data, LT recipients were classified by donor age: ≥70, 40-69, and <40 years. Recipient risk factors for one-year graft loss were identified and created a risk stratification system and validated it using 2020 OPTN/UNOS data set. At transplant, significant recipient risk factors for one-year graft loss were: previous liver transplant (adjusted hazard ratio [aHR] 4.37, 95%CI 1.98-9.65); mechanical ventilation (aHR 4.28, 95%CI 1.95-9.43); portal thrombus (aHR 1.87, 95%CI 1.26-2.77); serum sodium <125 mEq/L (aHR 2.88, 95%CI 1.34-6.20); and Karnofsky score 10-30% (aHR 2.03, 95%CI 1.13-3.65), 40-60% (aHR 1.65, 95%CI 1.08-2.51). Using those risk factors and multiplying HRs, recipients were divided into low-risk (n = 931) and high-risk (n = 294). Adjusted risk of one-year graft loss in the low-risk recipient group was similar to that of patients with younger donors; results were consistent using validation dataset. Our results show that a system of careful recipient selection can reduce the risks of graft loss associated with older donor age.

Improvements in liver transplant outcomes in patients with HCV/HIV coinfection after the introduction of direct-acting antiviral therapies.

BACKGROUND: In recipients with HCV/HIV coinfection, the impact that the wider use of direct-acting antivirals (DAAs) has had on post-liver transplant (LT) outcomes has not been evaluated. We investigated the impact of DAAs introduction on post-LT outcome in patients with HCV/HIV coinfection. METHODS: Using Organ Procurement and Transplant Network/United Network for Organ Sharing data, we compared post-LT outcomes in patients with HCV and/or HIV pre- and post-DAAs introduction. We categorized these patients into two eras: pre-DAA (2008-2012 [pre-DAA era]) and post-DAA (2014-2019 [post-DAA era]). To study the impact of DAAs introduction, inverse probability of treatment weighting was used to adjust patient characteristics. RESULTS: A total of 17 215 LT recipients were eligible for this study (HCV/HIV [n = 160]; HIV mono-infection [n = 188]; HCV mono-infection [n = 16 867]). HCV/HIV coinfection and HCV mono-infection had a significantly lower hazard of 1- and 3-year graft loss post-DAA, compared pre-DAA (1-year: adjusted hazard ratio [aHR] 0.29, 95% confidence interval (CI) 0.16-0.53 in HIV/HCV, aHR 0.58, 95% CI 0.54-0.63, respectively; 3-year: aHR 0.30, 95% CI 0.14-0.61, aHR 0.64, 95% CI 0.58-0.70, respectively). The hazards of 1- and 3-year graft loss post-DAA in HIV mono-infection were comparable to those in pre-DAA. HCV/HIV coinfection had significantly lower patient mortality post-DAA, compared to pre-DAA (1-year: aHR 0.30, 95% CI 0.17-0.55; 3-year: aHR 0.31, 95% CI 0.15-0.63). CONCLUSIONS: Post-LT outcomes in patients with coinfection significantly improved and became comparable to those with HCV mono-infection after introducing DAA therapy. The introduction of DAAs supports the use of LT in the setting of HCV/HIV coinfection.

Retransplantation outcomes for hepatitis C in the United States before and after direct-acting antiviral introduction.

The success of direct-acting antiviral (DAA) therapy has led to near-universal cure for patients chronically infected with hepatitis C virus (HCV) and improved post-liver transplant (LT) outcomes. We investigated the trends and outcomes of retransplantation in HCV and non-HCV patients before and after the introduction of DAA. Adult patients who underwent re-LT were identified in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Multiorgan transplants and patients with >2 total LTs were excluded. Two eras were defined: pre-DAA (2009-2012) and post-DAA (2014-2017). A total of 2112 re-LT patients were eligible (HCV: n = 499 pre-DAA and n = 322 post-DAA; non-HCV: n = 547 pre-DAA and n = 744 post-DAA). HCV patients had both improved graft and patient survival after re-LT in the post-DAA era. One-year graft survival was 69.8% pre-DAA and 83.8% post-DAA (P < .001). One-year patient survival was 73.1% pre-DAA and 86.2% post-DAA (P < .001). Graft and patient survival was similar between eras for non-HCV patients. When adjusted, the post-DAA era represented an independent positive predictive factor for graft and patient survival (hazard ratio [HR]: 0.67; P = .005, and HR: 0.65; P = .004) only in HCV patients. The positive post-DAA era effect was observed only in HCV patients with first graft loss due to disease recurrence (HR: 0.31; P = .002, HR 0.32; P = .003, respectively). Among HCV patients, receiving a re-LT in the post-DAA era was associated with improved patient and graft survival.

Outcomes in Living Donor Compared With Deceased Donor Primary Liver Transplantation in Lower Acuity Patients With Model for End-Stage Liver Disease Scores <30.

Although recent studies have reported favorable outcomes in living donor liver transplantation (LDLT), it remains unclear which populations benefit most from LDLT. This study aims to evaluate LDLT outcomes compared with deceased donor LT (DDLT) according to Model for End-Stage Liver Disease (MELD) score categories. Using data from the United Network for Organ Sharing registry, outcomes were compared between 1486 LDLTs; 13,568 donation after brain death (DBD)-DDLTs; and 1171 donation after circulatory death (DCD)-DDLTs between 2009 and 2018. Because LDLT for patients with MELD scores >30 was rare, all patients with scores >30 were excluded to equalize LDLT and DDLT cohorts. Risk factors for 1-year graft loss (GL) were determined separately for LDLT and DDLT. Compared with LDLT, DBD-DDLT had a lower risk of 30-day (adjusted hazard ratio [aHR], 0.60; P < 0.001) and 1-year GL (aHR, 0.57; P < 0.001). The lower risk of GL was more prominent in the mid-MELD score category (score 15-29). Compared with LDLT, DCD-DDLT had a lower risk of 30-day GL but a comparable risk of 1-year GL, regardless of MELD score category. In LDLT, significant ascites was an independent risk for GL in patients with mid-MELD scores (aHR, 1.68; P = 0.02), but not in the lower-MELD score group. The risk of 1-year GL in LDLT patients with ascites who received a left liver was higher than either those who received a right liver or those without ascites who received a left liver. In LDLT, combinations of MELD scores of 15 to 29, moderate/severe ascites, and the use of a left liver are associated with worse outcomes. These findings help calibrate appropriate patient and graft selection in LDLT.

Effect of Mandatory 6-Month Waiting Period on Waitlist and Transplant Outcomes in Patients With Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) policy mandates a 6-month waiting period before exception scores are granted to liver transplant candidates with hepatocellular carcinoma (HCC). This study aims to evaluate waitlist and posttransplant outcomes in patients with HCC, before and after implementation of the 6-month waiting rule. APPROACH AND RESULTS: We examined two groups from the UNOS registry: Group 1 (pre-6-month rule) consisted of patients registered as transplant candidates with HCC from January 1, 2013, to October 7, 2015 (n = 4,814); group 2 (post-6-month rule) consisted of patients registered from October 8, 2015, to June 30, 2018 (n = 3,287). As expected, the transplant probability was higher in the first 6 months after listing in group 1 than group 2 at 42.0% versus 6.3% (P < 0.001). However, the 6-month waitlist mortality/dropout rate was lower in group 2 at 1.2% than group 1 at 4.1% (P < 0.001). To assess regional parity of transplant, UNOS regions were categorized into three groups based on Model for End-Stage Liver Disease score at transplant: lower-score (regions 3, 10, and 11), middle-score (1, 2, 6, 8, and 9), and higher-score region groups (4, 5, and 7). Outcomes were compared from the time exception points were given, which we defined as conditional waitlist outcomes. Conditional waitlist mortality/dropout decreased, and transplant probability increased in all region groups, but the benefits of the policy were more pronounced in the higher and middle-score groups, compared with the lower-score group. The decline in waitlist mortality/dropout was only significant in the high Model for End-Stage Liver Disease group (P < 0.001). No effect was observed on posttransplant mortality or percent of patients within Milan criteria on explant. CONCLUSIONS: The HCC policy change was associated with decreased waitlist mortality/dropout and increased transplant probability. The policy helped to decrease but did not eliminate regional disparities in transplant opportunity without an effect on posttransplant outcomes.

Disease-specific waitlist outcomes in liver transplantation - a retrospective study.

This study aimed to evaluate possible discrepancies in waitlist outcomes between liver diseases, including alcohol-related liver disease (ALD), nonalcoholic steatohepatitis (NASH), hepatitis C virus infection (HCV), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). Patients registered for liver transplantation from January 11, 2016, to June 30, 2018, were evaluated using OPTN/UNOS registry. Waitlist outcomes were compared between the five-disease groups. Patients were categorized by initial MELD-Na-score (6-20, 21-29, and ≥30) to identify outcome variations. Prognostic impact of transplantation was assessed according to final MELD-Na scores using Cox regression analysis modeling transplantation as a time-dependent covariate. 6053 with ALD, 3814 with NASH, 1558 with HCV, 602 with PBC, and 819 with PSC were eligible. Compared to ALD with comparable MELD-Na-scores, NASH with lower [adjusted hazard ratio (aHR) = 1.30, P = 0.042] and mid-scores (aHR = 1.35, P = 0.008) showed significantly higher risk of 1-year waitlist mortality, and PBC with higher scores showed significantly higher risk of 90-day (aHR = 1.69, P = 0.03) and 1-year waitlist mortality (aHR = 1.69, P = 0.02). Positive prognostic impact of transplantation was not seen until score of 24-27 in ALD, 18-20 in HCV, 15-17 in NASH, and 24-27 in PBC and PSC. There are significant differences in waitlist outcomes among etiologies, which may differ the optimal transplant timing.

Extreme hyponatremia as a risk factor for early mortality after liver transplantation in the MELD-sodium era.

The impact of hyponatremia on waitlist and post-transplant outcomes following the implementation of MELD-Na-based liver allocation remains unclear. We investigated waitlist and postliver transplant (LT) outcomes in patients with hyponatremia before and after implementing MELD-Na-based allocation. Adult patients registered for a primary LT between 2009 and 2021 were identified in the OPTN/UNOS database. Two eras were defined; pre-MELD-Na and post-MELD-Na. Extreme hyponatremia was defined as a serum sodium concentration ≤120 mEq/l. Ninety-day waitlist outcomes and post-LT survival were compared using Fine-Gray proportional hazard and mixed-effects Cox proportional hazard models. A total of 118 487 patients were eligible (n = 64 940: pre-MELD-Na; n = 53 547: post-MELD-Na). In the pre-MELD-Na era, extreme hyponatremia at listing was associated with an increased risk of 90-day waitlist mortality ([ref: 135-145] HR: 3.80; 95% CI: 2.97-4.87; P < 0.001) and higher transplant probability (HR: 1.67; 95% CI: 1.38-2.01; P < 0.001). In the post-MELD-Na era, patients with extreme hyponatremia had a proportionally lower relative risk of waitlist mortality (HR: 2.27; 95% CI 1.60-3.23; P < 0.001) and proportionally higher transplant probability (HR: 2.12; 95% CI 1.76-2.55; P < 0.001) as patients with normal serum sodium levels (135-145). Extreme hyponatremia was associated with a higher risk of 90, 180, and 365-day post-LT survival compared to patients with normal serum sodium levels. With the introduction of MELD-Na-based allocation, waitlist outcomes have improved in patients with extreme hyponatremia but they continue to have worse short-term post-LT survival.

A Share 21 model in liver transplantation: Impact on waitlist outcomes.

With the introduction of Model for End-Stage Liver Disease-Sodium (MELD-Na)-based allocation, the score at which patients benefit from liver transplantation (LT) has shifted from a score of 15 to 21. This study aimed to evaluate waitlist outcomes in patients with MELD-Na scores <21 and explore the utility of replacing "Share 15" with "Share 21." The study uses data from the Organ Procurement and Transplantation Network/United Network for Organ Sharing registry. All adult patients registered for LT after implementation of the MELD-Na-based allocation were evaluated. Waitlist patients with initial and final scores <21 were eligible. Patients with exception scores were excluded. To explore the potential impact of a Share 21 model, patients with an initial MELD-Na score of 6-14 (Group 1) and those with a score of 15-20 (Group 2) were compared for waitlist outcomes. There were 3686 patients with an initial score of 6-14 (Group 1) and 3282 with a score of 15-20 (Group 2). Group 2, when compared to Group 1, showed comparable risk of mortality (adjusted hazard ratio [aHR] 1.00, P = .97), higher transplant probability (aHR 3.25, P < .001), and lower likelihood of removal from listing because of improvement (aHR 0.74, P = .011). Share 21 may enhance transplant opportunities and increase parity for patients with higher MELD-Na scores without compromising waitlist outcomes.

The molecular diagnosis of rejection in liver transplant biopsies: First results of the INTERLIVER study.

Molecular diagnosis of rejection is emerging in kidney, heart, and lung transplant biopsies and could offer insights for liver transplant biopsies. We measured gene expression by microarrays in 235 liver transplant biopsies from 10 centers. Unsupervised archetypal analysis based on expression of previously annotated rejection-related transcripts identified 4 groups: normal "R1normal " (N = 129), T cell-mediated rejection (TCMR) "R2TCMR " (N = 37), early injury "R3injury " (N = 61), and fibrosis "R4late " (N = 8). Groups differed in median time posttransplant, for example, R3injury 99 days vs R4late 3117 days. R2TCMR biopsies expressed typical TCMR-related transcripts, for example, intense IFNG-induced effects. R3injury displayed increased expression of parenchymal injury transcripts (eg, hypoxia-inducible factor EGLN1). R4late biopsies showed immunoglobulin transcripts and injury-related transcripts. R2TCMR correlated with histologic rejection although with many discrepancies, and R4late with fibrosis. R2TCMR , R3injury , and R4late correlated with liver function abnormalities. Supervised classifiers trained on histologic rejection showed less agreement with histology than unsupervised R2TCMR scores. No confirmed cases of clinical antibody-mediated rejection (ABMR) were present in the population, and strategies that previously revealed ABMR in kidney and heart transplants failed to reveal a liver ABMR phenotype. In conclusion, molecular analysis of liver transplant biopsies detects rejection, has the potential to resolve ambiguities, and could assist with immunosuppressive management.

Posttransplant Complications Predict Alcohol Relapse in Liver Transplant Recipients.

Alcohol relapse after liver transplantation (LT) in patients with alcohol-related liver disease (ALD) is a major challenge. Although its association with pretransplant psychosocial factors was extensively studied, the impacts of posttransplant courses on alcohol relapse have not been well investigated. The aim of this study is to analyze peritransplant factors associated with posttransplant alcohol relapse in patients with ALD. This study evaluated 190 adult LT patients with ALD from 2013 to 2019. Risk factors for alcohol relapse were analyzed, focusing on posttransplant chronic complications, which were classified as Clavien-Dindo classification 3a or higher that lasted over 30 days. The posttransplant alcohol relapse rate was 13.7% (26/190) with a median onset time of 18.6 months after transplant. Multivariate Cox regression analysis revealed that posttransplant chronic complications were an independent risk factor for posttransplant alcohol relapse (hazard ratio [HR], 5.40; P = 0.001), along with psychiatric comorbidity (HR, 3.93; P = 0.001), history of alcohol relapse before LT (HR, 3.00; P = 0.008), and an abstinence period <1.5 years (HR, 12.05; P = 0.001). A risk prediction model was created using 3 pretransplant risk factors (psychiatric comorbidity, alcohol relapse before LT, and abstinence period <1.5 years). This model clearly stratified the risk of alcohol relapse into high-, moderate-, and low-risk groups (P < 0.001). Of the 26 patients who relapsed, 11 (42.3%) continued drinking, of whom 3 died of severe alcoholic hepatitis, and 13 (50.0%) achieved sobriety (outcomes for 2 patients were unknown). In conclusion, posttransplant chronic complications increased the risk of alcohol relapse. Recognition of posttransplant chronic complications in conjunction with the risk stratification model by pretransplant psychosocial factors would help with the prediction of posttransplant alcohol relapse.

Center Experience Affects Liver Transplant Outcomes in Patients with Hilar Cholangiocarcinoma.

BACKGROUND: Based on favorable outcomes reported by experienced centers, perihilar cholangiocarcinoma (Ph-CCA) has become an accepted indication for liver transplantation (LT). What is less clear is if the reported outcomes have been reproduced nationwide in the US. OBJECTIVE: The aim of this study was to evaluate post-transplant outcomes in patients with Ph-CCA and to determine prognostic factors. METHODS: Patients who underwent LT with Model for End-stage Liver Disease exception scores for Ph-CCA between 2010 and 2017 were evaluated. Transplant centers were classified into well- and less-experienced groups: Group 1 [well-experienced (≥ 6 LTs), 7 centers]; Group 2 [less-experienced (< 6 LTs), 23 centers]. Post-transplant mortality due to all-cause and recurrence of Ph-CCA were set as endpoints. RESULTS: Post-transplant outcomes were significantly better in Group 1 than in Group 2, with 1-, 3-, and 5-year patient survival rates of 91.8%, 56.9%, and 45.8%, versus 65.6%, 48.8%, and 26.0%, respectively. Group 2 showed a significantly higher risk of 1-, 3-, and 5-year all-cause mortality and 1-year mortality associated with Ph-CCA recurrence. Center experience was an independent risk factor for post-transplant mortality. In intention-to-treat analysis, a positive prognostic effect of LT was significant and LT decreased the mortality risk by 86% in the well-experienced group [hazard ratio (HR) 0.14, p < 0.001], whereas this effect was not observed in the less-experienced group (HR 1.35, p = 0.47). CONCLUSIONS: Risk of recurrence of malignancy and mortality was significantly higher in the less-experienced center group. Center effects on post-transplant outcomes in patients with Ph-CCA should be recognized, and the introduction of center approval for LT for Ph-CCA may be justified to achieve comparable outcomes between centers.

Liver transplant waitlist outcomes in alcoholic hepatitis compared with other liver diseases: An analysis of UNOS registry.

There is growing interest in performing liver transplantation (LT) in patients with alcoholic hepatitis (AH) without a mandated abstinence period. The aim of this study is to investigate waitlist outcomes in AH patients compared to those with other liver diseases. Using data from the UNOS registry, adult patients listed for LT between 2009 and 2018 were evaluated. Waitlist outcomes were compared among liver diseases. A total of 64 646 patients were eligible, including 286 with AH, 16 871 with alcoholic cirrhosis (AC), 13 730 with hepatitis C (HCV), 10 315 with non-alcoholic steatohepatitis (NASH), and 5841 with cholestatic liver disease (CLD). In comparison with AH patients, patients with HCV, NASH, and CLD had a significantly higher risk of waitlist mortality and a lower likelihood of recovery on the waitlist. These trends were more prominent in the waiting-time period of 91-365 days than in shorter periods. In intention-to-treat analysis, positive prognostic effect of LT was significant in AH patients with MELD score ≥35 (HR 0.04, P < .001). AH patients showed lower mortality risk and a higher chance of recovery while on waitlist than other liver diseases, especially when waiting time exceeded 90 days. These results indicate the importance of continuous evaluation of disease progression in AH patients awaiting LT.

Effects of Allocating Livers for Transplantation Based on Model for End-Stage Liver Disease-Sodium Scores on Patient Outcomes.

BACKGROUND & AIMS: The Model for End-stage Liver Disease and Sodium (MELD-Na) score was introduced for liver allocation in January 2016. We evaluated the effects of liver allocation, based on MELD-Na score, on waitlist and post-transplantation outcomes. METHODS: We examined 2 patient groups from the United Network for Organ Sharing registry; the MELD-period group was composed of patients who were registered as transplant candidates from June 18, 2013 through January 10, 2016 (n = 18,850) and the MELD-Na period group was composed of patients who were registered from January 11, 2016 through September 30, 2017 (n = 14,512). We compared waitlist and post-transplantation outcomes and association with serum sodium concentrations between groups. RESULTS: Mortality within 90 days on the liver waitlist decreased (hazard ratio [HR] 0.738, P < .001) and transplantation probability increased significantly (HR 1.217, P < .001) in the MELD-Na period. Although mild, moderate, and severe hyponatremia (130-134, 125-129, and <125 mmol/L) were independent risk factors for waitlist mortality in the MELD period (HR 1.354, 1.762, and 2.656; P < .001, P < .001, and P < .001, respectively) compared with the reference standard (135-145 mmol/L), these adverse outcomes were decreased in the MELD-Na period (HR 1.092, 1.271 and 1.374; P = .27, P = .018, and P = .037, respectively). The adjusted survival benefit of transplant recipients vs patients placed on the waitlist in the same score categories was definitive for patients with MELD-Na scores of 21-23 in the MELD-Na era (HR 0.336, P < .001) compared with MELD scores of 15-17 in the MELD era (HR 0.365, P < .001). CONCLUSIONS: Liver allocation based on MELD-Na score successfully improved waitlist outcomes and provided significant benefit to hyponatremic patients. Given the discrepancy in transplantation survival benefit, the current rules for liver allocation might require revision.

Increased Risk of Death in First Year After Liver Transplantation Among Patients With Nonalcoholic Steatohepatitis vs Liver Disease of Other Etiologies.

BACKGROUND & AIMS: An increasing number of patients with non-alcoholic steatohepatitis (NASH) require liver transplantation. We compared outcomes of patients with liver diseases of different etiologies (NASH, hepatitis C virus [HCV]-associated liver disease, and alcohol-associated liver disease [ALD]). METHODS: We analyzed data from the United Network for Organ Sharing registry on 6344 patients who underwent liver transplantation for NASH, 17,037 for cirrhosis from chronic HCV infection, and 9279 for ALD. We collected data from patients who underwent liver transplantation during the following time periods: 2008-2010, 2011-2013, 2014-2015, 2016-2017. We compared outcomes of different groups using Cox regression models, adjusting for donor and recipient characteristics. RESULTS: For patients who underwent liver transplantation during 2016-2017, a significantly lower proportion of patients with NASH survived for 1 year after transplantation than patients with HCV (P = .004) or ALD (P < .001). During this time period, the adjusted risk of death within 1 year was significantly higher for patients with NASH than with ALD (hazard ratio, 1.37; P = .03), regardless of the presence of hepatocellular carcinoma. The effects of increasing age were greatest among patients with NASH: compared to patients younger than 50 years, hazard ratios for overall mortality were 1.31 for patients 50-59 years (P = .02), 1.66 for patients 60-64 years (P < .001), 2.08 for patients 65-69 years (P < .001), and 2.66 and for patients and ≥70 years (P < .001). Mortality from cardiovascular or cerebrovascular disease(s) was highest among patients with NASH, accounting for 11.5% of deaths, compared to 7.0% of deaths in patients with HCV infection and 9.6% in patients with ALD (P < .001). CONCLUSIONS: In an analysis of data from patients who underwent liver transplantation during 2016-2017, we found the risk of death within 1 year after transplant was higher among patients with NASH than HCV-associated liver disease or ALD. Risk of death increased with age, and patients with NASH have a higher risk of death from cardiovascular or cerebrovascular disease.

Racial disparities in patient selection for liver transplantation: An ongoing challenge.

Ample evidence suggests continued racial disparities once listed for liver transplantation, though few studies examine disparities in the selection process for listing. The objective of this study, via retrospective chart review, was to determine whether listing for liver transplantation was influenced by socioeconomic status and race/ethnicity. We identified 1968 patients with end-stage liver disease who underwent evaluation at a large, Midwestern center from January 1, 2004 through December 31, 2012 (72.9% white, 19.6% black, and 7.5% other). Over half (54.6%) of evaluated patients were listed; the three most common reasons for not listing were medical contraindications (11.9%), patient expired during evaluation (7.0%), and psychosocial contraindications (5.9%). In multivariable logistic regressions (listed vs not listed), across the three racial categories, the odds of being listed were lower for alcohol-induced hepatitis (±hepatitis C), unmarried, more than one insurance, inadequate insurance, and lower annual household income quartile. Similar factors predicted time to transplant listing, including being identified as black race. Black race, even when adjusting for the above mentioned medical and socioeconomic factors, was associated with 26% lower odds of being listed and a longer time to listing decision compared to all other patients.

Liver alone or simultaneous liver-kidney transplant? Pretransplant chronic kidney disease and post-transplant outcome - a retrospective study.

The new Organ Procurement and Transplant Network/United Organ Sharing Network (OPTN/UNOS) simultaneous liver-kidney transplant (SLK) policy has been implemented. The aim of this study was to review liver transplant outcomes utilizing the new SLK policy. Liver transplant alone (LTA) and SLK patients between 2009 and 2015 were reviewed. Graft survival and post-transplant kidney function were investigated among LTA patients meeting the chronic kidney disease (CKD) criteria of the new policy (LTA-CKD group). To validate our findings, we reviewed and applied our analysis to the OPTN/UNOS registry. A total of 535 patients were eligible from our series. The LTA-CKD group (n = 27) showed worse 1-year graft survival, compared with the SLK group (n = 44), but not significant (81% vs. 93%, P = 0.15). The LTA-CKD group significantly increased a risk of post-transplant dialysis (odds ratio = 5.59 [95% CI = 1.27-24.7], P = 0.02 [Ref. normal kidney function]). Post-transplant dialysis was an independent risk factor for graft loss (hazard ratio = 7.25, 95% CI = 3.3-15.91, P < 0.001 [Ref. SLK]). In the validation analysis based on the OPTN/UNOS registry, the hazard of 1-year-graft loss in the LTA-CKD group (n = 751) was 34.8% higher than the SLK group (n = 2856) (hazard ratio = 1.348, 95% CI = 1.157-1.572, P < 0.001). Indicating SLK for patients who meet the CKD criteria may significantly improve transplant outcomes.