Obesity is a worldwide epidemic and is pervasive in the liver disease community. Given that liver disease is both caused and worsened by obesity, our study assesses the risks of bariatric surgery in patients with chronic liver disease.

This retrospective study using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program 2023 database includes adult patients who underwent minimally invasive sleeve gastrectomy, Roux-en-Y gastric bypass, or gastric band placement procedures. Liver disease (LD) includes a spectrum of severity (borderline to moderate) and etiologies (including steatosis). LD and non-liver disease (non-LD) cohorts were compared using Chi-square and t-tests. Univariate and multivariate analyses were performed using logistic regression.

Our sample of 201,605 patients included 22,476 (11.2%) LD and 179,129 (88.9%) non-LD patients. Overall mean body mass index was 44.68 kg/m2 (SD 7.86). The mortality rates were no different between groups (0.07% and 0.07%, p = 0.85). While multivariate subset analyses of each procedure showed a statistically slightly elevated risk of bleeding, infection, bowel obstruction, Clavien-Dindo I-III complications, and ICU admission for the liver group patients (odds ratios ranged from 1.42-1.76), rates of complications were clinically very low (3.1% and 0.8% for Clavien-Dindo I-III and IV).

Given the low 30-day complication rate, our study shows that in the appropriate candidates with mild-to-moderate chronic liver disease, minimally invasive bariatric surgery is safe in the short-term, and the documented benefits of weight loss likely outweigh the slightly elevated risk. Bariatric surgeons can feel more comfortable and informed operating in this context.

Posttransplant diabetes mellitus (PTDM) is associated with significant morbidity and mortality in liver transplant recipients (LTRs). We used the Organ Procurement and Transplantation Network (OPTN) database to compare the incidence of developing PTDM across the United States and develop a risk prediction model for new-onset PTDM using OPTN region as well as donor-related, recipient-related, and transplant-related factors. All US adult, primary, deceased donor, LTRs between January 1, 2007, and December 31, 2016, with no prior history of diabetes noted , were identified. Kaplan-Meier estimators were used to calculate the cumulative incidence of PTDM, stratified by OPTN region. Multivariable Cox proportional hazards models were fitted to estimate hazards of PTDM in each OPTN region and build a risk prediction model, through backward selection. Cumulative incidence of PTDM at 1 year, 3 years, and 5 years after transplant was 12.0%, 16.1%, and 18.9%, respectively. Region 3, followed by regions 8, 2, and 9, had the highest adjusted hazards of developing PTDM. Inclusion of OPTN region in a risk prediction model for PTDM in LTRs (including recipient age, sex, race, education, insurance coverage, body mass index, primary liver disease, cold ischemia time, and donor history of diabetes) modestly improved performance (C-statistic = 0.60). In patients without pre-existing, confirmed diabetes mellitus, the incidence of PTDM in LTRs varied across OPTN regions, with the highest hazards in region 3, followed by regions 8, 2, and 9. The performance of a novel risk prediction model for PTDM in LTRs has improved performance with the inclusion of the OPTN region. Vigilance is recommended to centers in high-risk regions to identify PTDM and mitigate its development.

The current liver transplantation (LT) allocation policy focuses on the MELD scores, often overlooking factors like blood type and survival benefits. Understanding blood types' impact on survival benefits is crucial for optimizing the MELD 3.0 classification. This study used the United Network for Organ Sharing national registry database (2003-2020) to identify LT characteristics per ABO blood type and to determine the optimal MELD 3.0 scores for each blood type, based on survival benefits. The study included candidates of LT aged 18 years or older listed for LT (total N=150,815; A: 56,546, AB: 5841, B: 18,500, O: 69,928). Among these, 87,409 individuals (58.0%) underwent LT (A:32,156, AB: 4,362, B: 11,786, O: 39,105). Higher transplantation rates were observed in AB and B groups, with lower median MELD 3.0 scores at transplantation (AB: 21, B: 24 vs. A/O: 26, p <0.01) and shorter waiting times (AB: 101 d, B:172 d vs. A: 211 d, O: 201 d, p <0.01). A preference for donation after cardiac death (DCD) was seen in A and O recipients. Survival benefit analysis indicated that B blood type required higher MELD 3.0 scores for transplantation than A and O (donation after brain death transplantation: ≥15 in B vs. ≥11 in A/O; DCD transplantation: ≥21 in B vs. ≥11 in A, ≥15 in O). The study suggests revising the allocation policy to consider blood type for improved post-LT survival. This calls for personalized LT policies, recommending higher MELD 3.0 thresholds, particularly for individuals with type B blood.

Limited data exists regarding impact of graft type on outcomes following liver transplantation (LT) in Primary Sclerosing Cholangitis (PSC). Our goal was to evaluate the impact of graft type on outcomes following LT in PSC and determine predictors of outcomes.

Using the Scientific registry of transplant recipients (SRTR), retrospective cohorts were constructed of recipients with PSC over the time period 2010-2020, divided into 2 eras: 2010-2014, 2015-2020, stratified by graft type: living donor (LDLT), donation after circulatory death (DCD) and donation after brain death (DBD). Outcome measures evaluated were graft and patient survival. Survival comparison was performed using Kaplan-Meier method and multivariable analysis using Cox proportional hazard models.

2966 recipients underwent LT for PSC over the study period: LDLT-PSC 153 (5.2%), DCD-PSC 131 (4.4%) and DBD-PSC 2682 (90.4%). While LDLT utilization was higher in PSC (5.2% vs. 1.3%; p < 0.001), DCD use was lower (4.4% vs. 7.2%; p < 0.001) but increased over time (era 1 vs. era 2: 3.3% vs. 5.2%; p = 0.02). Outcomes following DCD-PSC were comparable to DBD and improved over time. Compared to DBD-PSC, there was a trend toward lower short-term graft survival following LDLT-PSC (1 Yr. 85.3 vs. 91.9; p = 0.07) with higher retransplant rate (LDLT-PSC vs. DCD-PSC vs. DBD-PSC: 15% vs 11% vs 7%; p < 0.001). Compared to recipients without PSC, long-term patient survival was superior in LDLT-PSC (5 Yr. 90.1 vs. 83.7%; p = 0.05) and DCD-PSC (93.3 vs. 79.7%, p = 0.01). On multivariable analysis, LDLT but not DCD graft type, was associated with inferior graft survival in PSC (adjusted hazard Ratio = 1.65 (1.16-2.34); p = 0.005).

In PSC, utilization of LDLT is higher, while DCD use is lower but increased over time. Outcomes following DCD LT in PSC are comparable to DBD and superior to recipients without PSC. Reduced graft survival and higher re-transplant rate following LDLT in PSC warrants further study. Consideration of DCD could help expand the donor pool in PSC.

To investigate the incidence and potential predictors of immune tolerance among adult living donor liver transplant (LDLT) recipients.

This case-control study included adult recipients who underwent LDLT between May 2004 and January 2018, with at least a 5-year follow-up after LDLT. We divided the study recipients into two groups: Group 1 (Tolerance Group) included recipients who achieved operational or prope tolerance for at least one year; Group 2 (Control Group) included recipients who did not achieve tolerance. We used logistic regression analysis to study the potential predictors of tolerance after LDLT.

We included 368 recipients, 275 (74.7%) in Group 1 and 93 (25.3%) in Group 2. Operational tolerance occurred in 13/275 (4.7%) recipients and prope tolerance in 262/275 (95.3%) recipients. Age was significantly higher in Group 1. The median time for tolerance among the study recipients was 60 months (36-168). During follow-up, Group 1 showed lower serum levels of bilirubin, liver enzymes, alkaline phosphatase, and gamma-glutamyl transferase. Group 1 had a lower incidence of acute cellular rejection (ACR), recurrent viral hepatitis, and biliary complications. Logistic regression identified preoperative MELD, indication for LDLT, ACR, recurrent viral hepatitis, and biliary complications as significant predictors for allograft tolerance after LDLT.

Allograft tolerance occurred in 74.7% of this cohort. We suggest that the MELD score, indication for LT, ACR, recurrent viral hepatitis, and biliary complications are predictors of allograft tolerance after LDLT.

Primary sclerosing cholangitis (PSC) is among the most common indications for liver transplantation in the Nordic countries and with an increasing trend in Europe and North America. Due to post-transplant complications and high prevalence of disease recurrence this group is at risk of requiring retransplantation (re-LTX). Results from re-LTX for PSC are not extensively studied and there is a lack of knowledge regarding prognosis after re-LTX in this population.

Graft and patient survival after re-LTX for patients with PSC and a comparable comparison group from the Nordic liver transplant registry were analysed. One-hundred and eighty-five patients with PSC and 208 patients in the comparison group were included.

The graft and patient survival were better for patients with PSC compared to the comparison group (p < 0.001). Re-LTX for recurrence of PSC (rPSC) compared to other aetiologies had similar and better outcomes for graft and patient survival (p = 0.093 and p = 0.023, respectively). Moreover, re-LTX for rPSC compared to the comparison group had a lower 30-day and 5-year mortality (p < 0.001 and p = 0.041, respectively).

Outcomes after retransplantation for PSC were similar or better compared to the comparison group. Retransplantation represents a treatment option with the potential for excellent outcomes in patients with PSC and should be considered in transplanted PSC patients with graft failure.

Prostaglandin E1 (PGE1), or alprostadil, is a potent vasodilator that improves hepatic blood flow and reduces ischemia-reperfusion injury post-liver transplantation (LT). However, the benefits of PGE1 on renal function after LT have not yet been well described.

To assess the impact of PGE1 administration on renal function in patients who underwent liver or liver-kidney transplant.

This retrospective study included all patients who underwent liver or liver-kidney transplant at our institution from January, 2011 to December, 2021. Patients were classified based on whether they received PGE1. PGE1 was administered post-LT to those with transaminases > 1000 U/L in the immediate postoperative period. Demographics, post-LT treatments and/or complications, renal function, and survival were analyzed. Multivariable logistic regression analysis was performed, and a two-tailed P value < 0.05 was considered statistically significant.

A total of 145 patients underwent LT, with 44 (30%) receiving PGE1. Baseline patient characteristics were comparable, except the PGE1 group had significantly higher aspartate aminotransferase (AST) (1961.9 U/L ± 1862.3 U/L vs 878 U/L ± 741.4 U/L, P = 0.000), alanine aminotransferase (1070.6 U/L ± 895 U/L vs 547.7 U/L ± 410 U/L, P = 0.000), international normalized ratio on post-LT day 1 (2 ± 0.74 vs 1.8 ± 0.4, P = 0.03), a longer intensive care unit stay (8.1 days ± 11.8 days vs 3.8 days ± 4.6 days, P = 0.003), more vasopressor use (55.53 hours ± 111 hours vs 16.33 hours ± 26.3 hours, P = 0.002), and higher immediate postoperative complications (18.6% vs 4.9%, P = 0.04). The PGE1 group also had a significantly higher 90-day readmission rate (29.6% vs 13.1%, P = 0.02) and lower 1-year liver graft survival (87.5% vs 98.9%, P = 0.005). However, 30-day readmission (31.6% vs 27.4%, P = 0.64), LT complications (hepatic artery thrombosis, biliary complications, rejection of liver graft, cardiomyopathy), 1-year patient survival (96.9% vs 97.8%, P = 0.77), overall liver graft survival, and overall patient survival were similar between the two groups (95.4% vs 93.9%, P = 0.74 and 88.4% vs 86.9%, P = 0.81 respectively). Although the PGE1 group had a significantly lower glomerular filtration rate (eGFR) on post-LT day 7 (46.3 mL/minute ± 26.7 mL/minute vs 62.5 mL/minute ± 34 mL/minute, P = 0.009), the eventual need for renal replacement therapy (13.6% vs 5.9%, P = 0.09), the number of dialysis sessions (0.91 vs 0.27, P = 0.13), and eGFR at 1-month (37.2 mL/minute ± 35.9 mL/minute vs 42 mL/minute ± 36.9 mL/minute, P = 0.49), 6-months (54.8 mL/minute ± 21.6 mL/minute vs 62 mL/minute ± 21.4 mL/minute, P = 0.09), and 12-months (63.7 mL/minute ± 20.7 mL/minute vs 62.8 mL/minute ± 20.3 mL/minute, P = 0.85) post-LT were similar to those in the non-PGE1 group.

In patients who received PGE1 for ischemia-reperfusion injury, despite immediate acute renal injury post-LT, the renal function at 1-month, 6-months, and 12-months post-LT was similar compared to those without ischemia-reperfusion injury. Prospective clinical trials are needed to further elucidate the benefits of PGE1 use in renal function.

WD repeat domain 83 opposite strand (WDR83OS) encodes the 106-aa (amino acid) protein Asterix, which heterodimerizes with CCDC47 to form the PAT (protein associated with ER translocon) complex. This complex functions as a chaperone for large proteins containing transmembrane domains to ensure proper folding. Until recently, little was known about the role of WDR83OS or CCDC47 in human disease traits. However, biallelic variants in CCDC47 were identified in four unrelated families with trichohepatoneurodevelopmental syndrome, characterized by a neurodevelopmental disorder (NDD) with liver dysfunction. Three affected siblings in an additional family share a homozygous truncating WDR83OS variant and a phenotype of NDD, dysmorphic features, and liver dysfunction. Using family-based rare variant analyses of exome sequencing (ES) data and case matching through GeneMatcher, we describe the clinical phenotypes of 11 additional individuals in eight unrelated families (nine unrelated families, 14 individuals in total) with biallelic putative truncating variants in WDR83OS. Consistent clinical features include NDD (14/14), facial dysmorphism (13/14), intractable itching (9/14), and elevated bile acids (5/6). Whereas bile acids were significantly elevated in 5/6 of individuals tested, bilirubin was normal and liver enzymes were normal to mildly elevated in all 14 individuals. In three of six individuals for whom longitudinal data were available, we observed a progressive reduction in relative head circumference. A zebrafish model lacking Wdr83os function further supports its role in the nervous system, craniofacial development, and lipid absorption. Taken together, our data support a disease-gene association between biallelic loss-of-function of WDR83OS and a neurological disease trait with hypercholanemia.

In this research, it was aimed to evaluate of social and community factors effective in increasing the number of liver donors. Descriptive and relational scanning models were used to conduct the research. Data on liver donors was gathered from the USA Health Resources & Services Administration's Organ Procurement and Transplantation Network between 1988 and 2023. The United States (USA) World Bank Country Reports provided the mortality rates. The data was analyzed using Spearman rho correlation, year-controlled partial correlation, and Generalized Linear Model-Logit analysis. Deceased donor numbers were significantly and negatively correlated with government health expenditure (r = -0.816; P < .01), current health expenditure (r = -0.768; P < .01), female education attainment (r = -0.804; P < .01) and Gini index (r = 0.434; P < .05). Living donor numbers were significantly and negatively correlated with government health expenditure (r = -0.731; P < .01), current health expenditure (r = -0.781; P < .01), male percentage (r = -0.786; P < .01), female education attainment (r = -0.640; P < .05), employment (r = 0.751; P < .01), GDP (r = -0.792; P < .01) and Gini index (r = -0.486; P < .01). Living donor numbers were significantly and positively correlated with age dependency (r = 0.815; P < .01). Generalized Linear Model-Logit (GLM-L) results showed that effect of female education attainment had significant contribution on deceased liver donor (B = -3290.605; P < .01). Effects of significantly correlated community factors on living liver donor numbers were found to be statistically insignificant (P > .05). Research findings reveal that among community factors, especially women's participation in education has a statistically significant effect on liver donors. These results show that the health expenditures made over the years do not provide any added value for liver donors, and role of women on liver donor is significantly dominant.

Alcohol-related liver disease is a leading cause of liver transplantation (LT) in the United States; however, alcohol relapse remains a risk, and real-world assessment of relapse prediction scores is lacking. The primary aim of this study was to assess risk factors for alcohol relapse and compare effectiveness of pre-existing risk scores (e.g., Sustained Alcohol Use Post-Liver Transplant (SALT) and Harmful Alcohol Use Post-Liver Transplant (HALT) scores).

This was a retrospective chart review of 69 adults who underwent LT for alcohol-related liver disease at Duke University Hospital from January 1, 2018, to January 1, 2021. Outcome variables included relapse post-LT, severity of relapse, and graft dysfunction.

Sixty-seven patients with a median follow-up time of 43 months were included. Eighteen (27%) experienced alcohol relapse. Of those, 16 (89%) had heavy alcohol use and 3 of those patients (17%) experienced graft dysfunction. Factors significantly associated with relapse included younger age, prior relapse, significant psychiatric comorbidities, alcohol use after cirrhosis diagnosis, shorter abstinence before LT listing, and prior alcohol treatment program. When applying SALT and HALT scores, the area under the curve was 0.69 (95% confidence interval 0.53-0.85) and 0.66 (95% confidence interval 0.50-0.81), respectively.

In our cohort, heavy alcohol use before transplantation and legal issues did not predict relapse, which are common components of prediction scores. Less than 5% of patients had graft dysfunction due to relapse, suggesting good graft outcomes. While the HALT and SALT scores were validated in our cohort, our finding of additional significant predictors of relapse, in addition to previously reported risk factors providing protective effect, suggests opportunity for further optimization of prediction scores.

To study the effects of routine HLA screening and the policy of avoiding donor-dominant one-way HLA match to prevent graft-versus-host disease (GVHD) after living donor liver transplantation (LDLT).

The records of potential living liver donors and recipients who attended our center between 2007 and 2018 were reviewed retrospectively.

Of the 149 patients who underwent LDLT and survived longer than 3 months, two developed GVHD despite our strict policy. The first patient presented with grade II GVHD limited to the skin. She was treated successfully by briefly discontinuing immunosuppression and switching to everolimus. In the second case, the policy had been relaxed due to the availability of a single donor for ABO-incompatible transplantation without any intervention to decrease anti-A antibody levels (special case: A2 to O). Nevertheless, the patient presented with grade I GVHD limited to skin and was treated successfully by adding oral methylprednisolone to tacrolimus and mycophenolate mofetil. To the best of our information, this is the second reported case who recovered from GVHD after LDLT from a donor, homozygous at HLA A, B and DR and a recipient, heterozygous for all. Sixteen potential donors (1.2% of all candidates) of 14 recipients were disqualified solely on the basis of the HLA results; five of these patients died due to unavailability of another donor.

The results support the policy of avoiding HLA combinations that preclude immune recognition of graft lymphocytes as foreign to decrease the risk of GVHD after LDLT.

Since the first liver transplant was performed over six decades ago, the landscape of liver transplantation in the US has seen dramatic evolution. Numerous advancements in perioperative and operative techniques have resulted in major improvements in graft and patient survival rates. Despite the increase in transplants performed over the years, the waitlist mortality rate continues to remain high. The obesity epidemic and the resultant metabolic sequelae continue to result in more marginal donors and challenging recipients. In this review, we aim to highlight the changing characteristics of liver transplant recipients and liver allograft donors. We focus on issues relevant in successfully transplanting a high model for end stage liver disease recipient. We provide insights into the current use of terms and definitions utilized to discuss marginal allografts, discuss the need to look into more consistent ways to describe these organs and propose two new concepts we coin as "Liver Allograft Variables" (LAV) and "Liver Allograft Composite Score" (LACS) for this. We discuss the development of spectrum of risk indexes as a dynamic tool to characterize an allograft in real time. We believe that this concept has the potential to optimize the way we allocate, utilize and transplant livers across the US.

Obesity is frequent among organ transplant recipients, increasing the risk of acute graft rejection and overall morbimortality. Laparoscopic sleeve gastrectomy (LSG) effectively improves graft survival and associated comorbidities. We first compared 30-d outcomes between chronic immunosuppressed (CI) and nonchronic immunosuppressed (non-CI) patients. Then, between organ transplant and non-organ transplant CI patients who underwent LSG.

Patients who underwent LSG within the metabolic and bariatric surgery accreditation and quality improvement program 2017-2019 were included. Using 1:1 and 1:4 propensity score matching analysis, the cohorts were matched for 30 characteristics. We then compared 30-d outcomes between CI and non-CI (analysis 1) and between organ transplant and non-organ transplant CI patients who underwent LSG (analysis 2).

A total of 486,576 patients were included. The matched cohorts in analysis 1 (n = 8978) and analysis 2 (n = 1152, n = 371) had similar preoperative characteristics. Propensity score matching in analysis 1 showed that patients in the CI group had significantly higher rates of renal complications (0.4% versus 0.2%, P = 0.006), unplanned intensive care unit admission (1.1% versus 0.7%, P = 0.003), blood transfusions (1.1% versus 0.7%, P = 0.003), readmissions (4.6% versus 3.5%, P < 0.001), reoperations (1.4% versus 1.0%, P = 0.033), interventions (1.3% versus 1.0%, P = 0.026), and postoperative bleeding (0.6% versus 0.4%, P = 0.013). In analysis 2, patients with organ transplant CI had a higher rate of pulmonary complications (1.1% versus 0.3%, P = 0.043), renal complications (2.4% versus 0.2%, P < 0.001), blood transfusions (6.5% versus 1.3%, P < 0.001), and readmissions (10.0% versus 4.6%, P < 0.001).

Patients with transplant-related CI who underwent LSG have higher 30-d postoperative complication rates compared to nontransplant-related CI patients; however, there were no differences in terms of mortality, intensive care unit admissions, staple line leaks, or bleeding. LSG is safe and feasible in this high-risk population.

Cardiovascular disease (CVD) is a leading complication after liver transplantation and has a significant impact on patients' outcomes posttransplant. The major risk factors for post-liver transplant CVD are age, preexisting CVD, nonalcoholic fatty liver disease, chronic kidney disease, and metabolic syndrome. This review explores the contemporary strategies and approaches to minimizing cardiometabolic disease burden in liver transplant recipients. We highlight areas for potential intervention to reduce the mortality of patients with metabolic syndrome and CVD after liver transplantation.

Tacrolimus is a potent macrolide immunosuppressant frequently used to prevent graft rejection in organ transplantation. Despite the known side effect of hemorrhage, there are no extensive descriptive series of patients who experience hemorrhage events associated with tacrolimus. We sought to review and describe tacrolimus-related hemorrhage events reported by healthcare professionals to the United States Food and Drug Association Adverse Event Reporting System (FAERS) database.

The FAERS database (2004q1-2022q4) was retrospectively analyzed to characterize reporting of hemorrhage adverse events (AEs) with tacrolimus. Subgroup analysis was completed on the hemorrhage.

A total of 75,310 tacrolimus-associated AEs were identified, of which 1,511 cases met specific inclusion/exclusion criteria with most occurring in the gastrointestinal tract (422 cases, 27.93% of all included cases). Death was reported in 558 patients (36.93% of hemorrhage cases), the most of which occurred in cases of brain hemorrhage (219 cases, 39.25% of death cases). Among definitive organ transplants, renal transplant was the most common indication for tacrolimus (62 cases, 4.10%) followed by bone marrow transplant (44 cases, 2.91%) and liver transplant (30 cases, 1.99%).

This study presents the largest collective description of tacrolimus-related hemorrhage events. We additionally described a number of previously unreported tacrolimus-related hemorrhage events.

Remote ischemic conditioning (RIC) has shown great advantages in protecting organs from ischemia-reperfusion loss and applied research on RIC continues to increase. We performed a systematic review and meta-analysis to comprehensively investigate the value of RIC for different organ transplantation.

We searched PubMed, EMBASE, and the Cochrane Library from inception to November 1, 2023, for randomized controlled trials investigating whether RIC has an advantage in organ transplantation (including heart, lung, liver, and kidney) compared with controls. The primary outcomes varied according to the transplanted organ, including liver transplantation (graft loss, early allograft dysfunction, acute kidney injury, days in hospital, and mortality); kidney transplantation (delayed graft function, acute rejection (AR), graft loss, 50% decrease in serum creatinine, glomerular filtration rate, days in hospital, and mortality); heart and lung transplantation (AR, mortality). Two investigators independently selected suitable trials, assessed trial quality, and extracted the data.

A total of 11 randomized controlled trials were included in this study, including six kidney transplants, three liver transplants, and one heart and lung transplant each, with 561 RIC cases and 564 controls, and a total of 1125 patients. The results showed that RIC did not reduce mortality in transplant patients compared with controls (liver transplant: RR0.9, 95% confidence interval [0.31-2.66]; kidney transplant: RR 0.76, 95% confidence interval [0.17-3.33]), graft failure rate (liver transplantation: RR 0.3, 95% confidence interval [0.07, 1.19]; kidney transplantation: RR 0.89, 95% confidence interval [0.35, 2.27]), length of hospital stay (liver transplantation: standard mean difference [SMD] 0.14, 95% confidence interval [-0.15, 0.42]; kidney transplantation: SMD -0.1, 95% confidence interval [-0.3, 0.11]). In addition, RIC did not improve early liver function after liver transplantation (RR 0.97, 95% confidence interval [0.55,1.7]), acute kidney injury after liver transplantation (RR 1.17 95% confidence interval [0.9, 1.54]), delayed functional recovery after renal transplantation (RR 0.84, 95% confidence interval [0.62, 1.15]), AR rate (RR 1.04, 95% confidence interval [0.72, 1.49]), 50% serum creatinine decline rate (RR 1.1, 95% confidence interval [0.88, 1.37]), glomerular filtration rate 3 months after surgery (SMD 0.13, 95% confidence interval [-0.05, 0.31]) and postoperative 12 months glomerular filtration rate (SMD 0.13, 95% confidence interval [-0.06, 0.31]).

Remote ischemic modulation does not improve clinical outcomes in patients undergoing organ transplantation (heart, lung, liver, and kidney).

Liver transplantation is an alternative treatment for patients with nonresectable colorectal cancer liver-only metastases (CRLM); however, the potential effects on wait-list time and life expectancy to other patients on the transplant waiting list have not been considered. We explored the potential effects of expanding liver transplantation eligibility to include patients with CRLM on wait-list time and life expectancy in Norway.

We developed a discrete event simulation model to reflect the Norwegian liver transplantation waiting list process and included 2 groups: 1) patients currently eligible for liver transplantation and 2) CRLM patients. Under 2 alternative CRLM-patient transplant eligibility criteria, we simulated 2 strategies: 1) inclusion of only currently eligible patients (CRLM patients received standard-of-care palliative chemotherapy) and 2) expanding waiting list eligibility to include CRLM patients under 2 eligibility criteria. Model outcomes included median waiting list time, life expectancy, and total life-years.

For every additional CRLM patient listed per year, the overall median wait-list time, initially 52 d, increased by 8% to 11%. Adding 2 additional CRLM patients under the most restrictive eligibility criteria increased the CRLM patients' average life expectancy by 10.64 y and decreased the average life expectancy for currently eligible patients by 0.05 y. Under these assumptions, there was a net gain of 149.61 life-years over a 10-y programmatic period, which continued to increase under scenarios of adding 10 CRLM patients to the wait-list. Health gains were lower under less restrictive CRLM eligibility criteria. For example, adding 4 additional CRLM patients under the less restrictive eligibility criteria increased the CRLM patients' average life expectancy by 5.64 y and decreased the average life expectancy for currently eligible patients by 0.12 y. Under these assumptions, there was a net gain of 96.36 life-years over a 10-y programmatic period, which continued to increase up to 7 CRLM patients.

Our model-based analysis enabled the consideration of the potential effects of enlisting Norwegian CRLM patients for liver transplantation on wait-list time and life expectancy. Enlisting CRLM patients is expected to increase the total health effects, which supports the implementation of liver transplantation for CRLM patients in Norway.

Given the Norwegian donor liver availability, adding patients with nonresectable colorectal cancer liver-only metastases (CRLM) to the liver transplantation waiting list had an overall modest, but varying, impact on total waiting list time.Survival gains for selected CRLM patients treated with liver transplantation would likely outweigh the losses incurred to patients listed currently.To improve the total life-years gained in the population, Norway should consider expanding the treatment options for CRLM patients to include liver transplantation.Other countries may also have an opportunity to gain total life-years by extending the waiting list eligibility criteria; however, country-specific analyses are required.

Long-term medical and quality of life (QOL) outcomes in voluntary liver donors remain under investigated. The objective of the current study was to report long-term medical outcomes and re-evaluate QOL in living liver donors.

This was a single-center retrospective cohort study of donors who underwent donor hepatectomy between 2012 and 2018. We investigated long-term outcomes in 7 domains. These include medical problems, surgical procedures, work-related issues, pregnancy outcomes, psychiatric interventions, willingness to donate again, and long-term mortality. QOL was evaluated using short-form 36.

The median follow-up time was 61.4 months (53.3-83.7). Among 698 donors, 80 (11.5%) experienced medical problems, 4 (0.6%) had work-related issues, and 20 (2.9%) needed psychiatric assistance. Surgery was performed in 49 donors (7%), and females were more likely to have undergone incisional hernia repair (5.8% vs 1.9%, P = .006). There were 79 postdonation pregnancies including 41 normal vaginal deliveries (51.9%), 35 cesarean sections (44.3%), and 3 miscarriages (3.8%). Willingness to donate again was reported by 658 donors (94.3%). Donors whose recipients were alive were more likely to donate again (95.5% vs 90.5%, P = .01). There were 3 deaths (0.4%) in the long-term. The mean physical composite score at initial and follow-up evaluation was 86.7 ± 13.9 and 76.5 ± 20.9 (P = .001), and the mean mental composite score at initial and follow-up evaluation was 92.1 ± 13.5 and 80.7 ± 16 (P = .001).

The overall long-term outlook in living liver donors is promising. QOL parameters might deteriorate over time and frequent re-evaluation might be considered.

New deceased donor liver allocation policy using an acuity circle (AC)-based model was implemented on February 4th, 2020. The effect of AC policy on simultaneous liver-kidney transplantation (SLKT) remains unknown. The aim of this study was to assess the effect of AC policy on SLKT waitlist mortality, transplant probability, and post-transplant outcomes.

Using the United Network for Organ Sharing database, 4908 adult SLKT candidates during two study periods, pre-AC (Aug-2017 to Feb-2020, N = 2770) and post-AC (Feb-2020 to Dec-2021, N = 2138) were analyzed. Outcomes included 90-day waitlist mortality, transplant probability, and post-transplant patient and graft survival.

Compared to pre-AC period, SLKT recipients during post-AC period had higher median model for end-stage liver disease (MELD) score (24 vs 23, P < 0.001), and less percentage of MELD exception (4.6% vs 7.7%, P = 0.001). The 90-day waitlist mortality was same, but the probability of SLKT increased in post-AC period (P < 0.001). Post-AC period also saw increased utilization of donation after cardiac death organs (11% vs 6.4%, P < 0.001) and decreased rates of transplantation among Black candidates (7.9% vs 13%). After risk adjustment, post-AC period was not associated with any significant difference in 90-day waitlist mortality (sub-distribution hazard ratio [sHR] 0.80; 95% CI 0.56-1.16, P = 0.24), and a higher 90-day probability of SLKT (sHR 1.68; 95% CI 1.41-1.99, P < 0.001). During post-transplant period, one-year patient survival, liver and kidney graft survival were comparable between two study periods.

The AC liver allocation policy was associated with increased transplant probability of adult SLKT candidates without decreasing waitlist mortality, post-transplant patient survival, or liver and kidney graft survival.

The MELD (model for end-stage liver disease) 3.0 score was developed to replace the MELD-Na score that is currently used to prioritize liver allocation for cirrhotic patients awaiting liver transplantation in the United States. The MELD 3.0 calculator includes new inputs from patient sex and serum albumin levels and has new weights for serum sodium, bilirubin, international normalized ratio, and creatinine levels. It is expected that use of MELD 3.0 scores will reduce overall waitlist mortality modestly and improve access for female liver transplant candidates. The utility of MELD 3.0 and PELDcre (pediatric end-stage liver disease, creatinine) scores for risk stratification in cirrhotic patients undergoing major abdominal surgery, placement of a transjugular intrahepatic portosystemic shunt, and other interventions requires further study. This article reviews the background of the MELD score and the rationale to create MELD 3.0 as well as potential implications of using this newer risk stratification tool in clinical practice.

Older liver transplant recipients have a lower risk of acute rejection than younger patients (9% for patients aged ≥65 years versus 23% for those aged 18-34 years) and are more vulnerable to immunosuppression-related complications. The number of liver transplant recipients ≥65 years has risen to 22% in Europe and the US, but limited information is available on the optimal immunosuppressive regimen for these patients. In this review, we discuss the appropriate management of immunosuppressive agents in older adults to minimize adverse events while avoiding acute rejection. The way the body processes drugs greatly depends on age. In the case of calcineurin inhibitor drugs, aging reduces hepatic metabolism, leading to changes in their pharmacokinetics. Corticosteroids also show decreased clearance as the patient ages. In severe cases of hypoalbuminemia, dose adjustment of mycophenolate acid derivatives may be necessary. However, the pharmacokinetic profiles of the mammalian target of rapamycin inhibitors, basiliximab, and rabbit anti-thymocyte globulin remain unaffected by age. Furthermore, age-related frailty may impact drug metabolism and require tailored interventions and closer follow-up. Although there is limited research, elderly liver transplant recipients require less immunosuppression with double or triple-agent regimens, lower exposure to calcineurin inhibitors, and a shorter course of corticosteroids. The usage of mammalian target of rapamycin inhibitors in older transplant populations has not been specifically investigated, and thus their usage should align with indications for younger patient groups.

Ischemia-reperfusion injury (IRI) during orthotopic liver transplantation (OLT) contributes to graft rejection and poor clinical outcomes. The disulfide form of high mobility group box 1 (diS-HMGB1), an intracellular protein released during OLT-IRI, induces pro-inflammatory macrophages. How diS-HMGB1 differentiates human monocytes into macrophages capable of activating adaptive immunity remains unknown. We investigated if diS-HMGB1 binds toll-like receptor (TLR) 4 and TLR9 to differentiate monocytes into pro-inflammatory macrophages that activate adaptive immunity and promote graft injury and dysfunction. Assessment of 106 clinical liver tissue and longitudinal blood samples revealed that OLT recipients were more likely to experience IRI and graft dysfunction with increased diS-HMGB1 released during reperfusion. Increased diS-HMGB1 concentration also correlated with TLR4/TLR9 activation, polarization of monocytes into pro-inflammatory macrophages, and production of anti-donor antibodies. In vitro, healthy volunteer monocytes stimulated with purified diS-HMGB1 had increased inflammatory cytokine secretion, antigen presentation machinery, and reactive oxygen species production. TLR4 inhibition primarily impeded cytokine/chemokine and costimulatory molecule programs, whereas TLR9 inhibition decreased HLA-DR and reactive oxygen species production. diS-HMGB1-polarized macrophages also showed increased capacity to present antigens and activate T memory cells. In murine OLT, diS-HMGB1 treatment potentiated ischemia-reperfusion-mediated hepatocellular injury, accompanied by increased serum alanine transaminase levels. This translational study identifies the diS-HMGB1/TLR4/TLR9 axis as potential therapeutic targets in OLT-IRI recipients.

Many real-life treatments are of limited supply and cannot be provided to all individuals in the population. For example, patients on the liver transplant waiting list usually cannot be assigned a liver transplant immediately at the time they reach highest priority because a suitable organ is not immediately available. In settings with limited supply, investigators are often interested in the effects of treatment strategies in which a limited proportion of patients receive an organ at a given time, that is, treatment regimes satisfying resource constraints. Here, we describe an estimand that allows us to define causal effects of treatment strategies that satisfy resource constraints: incremental propensity score interventions (IPSIs) for limited resources. IPSIs flexibly constrain time-varying resource utilization through proportional scaling of patients' natural propensities for treatment, thereby preserving existing propensity rank ordering compared to the status quo. We derive a simple class of inverse-probability-weighted estimators, and we apply one such estimator to evaluate the effect of restricting or expanding utilization of "increased risk" liver organs to treat patients with end-stage liver disease.

Introduction: Previous research has shown limited palliative care (PC) utilization among patients evaluated for liver transplantation (LT) despite the cohort's significant symptom burden, high frequency of hospitalization and risk of rapid decompensation. Our aim was to evaluate patient characteristics and end-of-life (EOL) outcomes (i.e. ICU utilization, code status, advance care planning) associated with the use of PC services in patients who were evaluated for LT. Methods: We performed a single-center cross-sectional study comprised of 223 deceased patients evaluated for LT between 1/1/2017 and 12/31/2021. We evaluated demographic characteristics and EOL outcomes for differences between patients who received PC consultation and those who did not. EOL outcomes associated with PC use were assessed using logistic and linear regression analysis adjusted for patient demographics. Results: Patients who received PC consultation were younger (mean 57 vs. 61; P = 0.048), had higher Model for end-stage Liver Disease (MELD) scores (27.5 vs. 22; P = 0.001), higher rates of hepatic encephalopathy (96% vs. 84%, P = 0.005), and were more frequently declined for LT (77% vs. 57%; P = 0.008). Patients who received PC services were less likely to die in the ICU (OR = 0.07 [0.02-0.18]) and were more likely to have documented advance care planning (OR = 3.16 [1.47-6.97]), family meetings (OR = 6.58 [2.72-17.08]), and goals-of-care discussions (OR = 14.83 [4.39-69.29]). Conclusion: For patients being evaluated for LT, PC utilization differed based on demographics, disease complications and severity, and transplant status. Those who received PC services had higher quality EOL care planning and fewer ICU admissions.

The post-operative course after Liver Transplantation (LT) can be complicated by early allograft dysfunction (EAD), primary nonfunction (PNF) and death. A lactate concentration at the end of transplant of ≥5 mmol/L was recently proposed as a predictive marker of PNF, EAD, and mortality; this study aimed to validate these previous reports in a large single center cohort.

This retrospective cohort study included adult liver transplant recipients who received grafts from deceased donors at our center between June 2012 and May 2021. Receiver operating characteristic (ROC) curves for the lactate concentration at the end of transplantation were computed to determine the AUC for PNF, EAD and mortality at 90 days.

In our cohort of 1137 cases, the AUCs for lactate to predict EAD, PNF and mortality were respectively .56 (95% confidence interval [CI]: .53-.60), .69 (95% CI: .52-.85), and .74 (95% CI: .63-.84).

The clinical value of lactate concentration at the end of transplantation to predict PNF, EAD and mortality at 90 days was, at best, modest, as shown by the relatively low AUCs. Our findings cannot validate previous reports that the lactate level alone is a good predictor of poor outcomes after liver transplantation.

Liver transplantation is a life-saving procedure for end-stage liver disease. However, post-transplant medication regimens are complex and non-adherence is common. Post-transplant medication non-adherence is associated with graft rejection, which can have long-term adverse consequences. Transplant centres are equipped with clinical staff that monitor patients post-transplant; however, digital health tools and proactive immunosuppression adherence monitoring has potential to improve outcomes.

This is a patient-randomised prospective clinical trial at three transplant centres in the Northeast, Midwest and South to investigate the effects of a remotely administered adherence programme compared with usual care. The programme monitors potential non-adherence largely levering text message prompts and phenotypes the nature of the non-adhere as cognitive, psychological, medical, social or economic. Additional reminders for medications, clinical appointments and routine self-management support are incorporated to promote adherence to the entire medical regimen. The primary study outcome is medication adherence via 24-hour recall; secondary outcomes include additional medication adherence (ASK-12 self-reported scale, regimen knowledge scales, tacrolimus values), quality of life, functional health status and clinical outcomes (eg, days hospitalised). Study implementation, acceptability, feasibility, costs and potential cost-effectiveness will also be evaluated.

The University of Pennsylvania Review Board has approved the study as the single IRB of record (protocol # 849575, V.1.4). Results will be published in peer-reviewed journals and summaries will be provided to study funders.

NCT05260268.

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

Liver transplantation (LT) is being increasingly performed for alcohol-related liver disease (ALD). It is unclear whether the increasing frequency of LTs in ALD patients has a negative impact on deceased-donor (DDLT) allocation and whether the current policy of 6 months of abstinence before transplantation effectively prevents recidivism after transplantation or improves long-term outcomes.

A total of 506 adult LT recipients, including 97 ALD patients, were enrolled. The outcomes of ALD patients were compared with those of non-ALD patients. The 97 ALD patients were further divided into group A (6-month abstinence) and group N (nonabstinence) based on the pretransplant alcohol withdrawal period. The incidence of relapsed drinking and the long-term outcomes were compared between the two groups.

The prevalence of LT for ALD significantly increased after 2016 (27.0% vs 14.0%; p < 0.01), but the frequency of DDLT for ALD remained unchanged (22.6% vs 34.1%, p = 0.210). After a median follow-up of 56.9 months, patient survival was comparable between the ALD and non-ALD patients (1, 3, and 5 years posttransplant: 87.6%, 84.3%, and 79.5% vs 82.8%, 76.6%, and 72.2%, respectively; p = 0.396). The results were consistent irrespective of the transplant type and disease severity. In ALD patients, 22 of the 70 (31.4%) patients reported relapsed drinking after transplantation, and the prevalence in group A had a higher tendency than that in group N (38.3% vs 17.4%, p = 0.077). Six months of abstinence or nonabstinence did not result in a survival difference, and de novo malignancies were the leading cause of late patient death in ALD patients.

LT achieves favorable outcomes for ALD patients. Six months of abstinence pretransplant did not predict the risk of recidivism after transplantation. The high incidence of de novo malignancies in these patients warrants a more comprehensive physical evaluation and better lifestyle modifications to improve long-term outcomes.

As a metabolic organ, the liver plays a variety of roles, including detoxification. It has been difficult to obtain stable supplies of hepatocytes for transplantation and for accurate hepatotoxicity determination in drug discovery research. Human pluripotent stem cells, capable of unlimited self-renewal, may be a promising source of hepatocytes. In order to develop a stable supply of embryonic stem cell (ESC)-derived hepatocytes, we have purified human ESC-derived hepatic progenitor cells with exposure to cytocidal puromycin by using their ability to metabolize drugs. Hepatic progenitor cells stably proliferated at least 220-fold over 120 days, maintaining hepatic progenitor cell-like properties. High drug-metabolizing hepatic progenitor cells can be matured into liver cells by suppressing hepatic proliferative signals. The method we developed enables the isolation and proliferation of functional hepatic progenitors from human ESCs, thereby providing a stable supply of high-quality cell resources at high efficiency. Cells produced by this method may facilitate cell therapy for hepatic diseases and reliable drug discovery research.

Alcohol-related liver disease (ALD) is among the most common indications for liver transplantation (LTX) in Europe and North America, with good five-year survival rates post-LTX. Here we evaluated survival up to and beyond 20 years after LTX for patients with ALD compared to a comparison group.

Patients with ALD and a comparison group transplanted in the Nordic countries between 1982 and 2020 were included. Data were analyzed using descriptive statistics, Kaplan-Meier curves and predictors of survival were assessed with Cox-regressions.

831 patients with ALD and 2979 patients in the comparison group were included in the study. Patients with ALD were older at the time of LTX (p < .001) and more likely to be male (p < .001). The estimated median follow-up time was 9.1 years for the ALD-group and 11.1 years for the comparison group. 333 (40.1%) patients with ALD and 1010 (33.9%) patients in the comparison group died during follow-up. The overall survival was impaired for patients with ALD compared to the comparison group (p < .001) and was evident for male and female patients, patients transplanted before and after 2005, and observed in all age-groups except patients over 60 years. Age at transplant, waiting time, year of LTX and country of LTX were associated with decreased survival after LTX for patients with ALD.

Patients with ALD have a decreased long-term survival following LTX. This difference was evident in most sub-groups of patients and warrants close follow-up of liver transplanted patients with ALD with focus on risk reduction.

Liver transplantation offers live-saving therapy for patients with complications of cirrhosis and stage T2 hepatocellular carcinoma. The demand for organs far outstrips the supply, and innovations aimed at increasing the number of usable deceased donors as well as alternative donor sources are a major focus. The etiologies of cirrhosis are shifting over time, with more need for transplantation among patients with alcohol-associated liver disease and nonalcoholic/metabolic fatty liver disease and less for viral hepatitis, although hepatitis B remains an important indication for transplant in countries with high endemicity. The rise in transplantation for alcohol-associated liver disease and nonalcoholic/metabolic fatty liver disease has brought attention to how patients are selected for transplantation and the strategies needed to prevent recurrent disease. In this review, we present a status report on the most pressing topics in liver transplantation and future challenges.

Epstein-Barr virus (EBV) infection and posttransplant lymphoproliferative disorders (PTLDs) after pediatric liver transplantation (LT) account for significant morbidity and mortality. Knowledge of EBV kinetics, epidemiology, and outcomes among pediatric living-donor LT cases is largely lacking. This study aims to provide clinical information related to EBV infection, chronic high EBV load (CHL) carriage, and PTLD at a living-donor-dominant pediatric LT center.

A total of 5827 EBV load measurements from 394 LT recipients fulfilling inclusion criteria and their clinical data were analyzed. EBV loads >1000 copies/μg DNA (742 IU/μg DNA) were considered "high," and CHL was defined by persistence >6 mo.

The highlighted results were as follows: (1) 94% of recipients underwent living-donor LT; (2) 80% of EBV seronegative recipients developed first EBV infection <2 y post-LT, and their EBV loads were consistently higher than those of seropositive recipients within <3 y post-LT but did not differ thereafter; (3) 61 (15%) recipients met CHL criteria, but none developed PTLD; (4) age <5 y, cytomegalovirus seronegative donors, and early development of EBV DNAemia <6 mo post-LT were independent risk factors for CHL; (5) the incidence of rejections after 1-y post-LT was comparably low among CHL carriers whose immunosuppression was minimized.

Early detection of EBV following LT and CMV seronegative donors would facilitate risk stratification to prevent PTLD while titrating immunosuppression among pediatric LT recipients.

Simultaneous liver-kidney transplantation (SLKT) is increasingly used for patients with concurrent end-stage liver and renal disease. Emerging evidence suggests that simultaneous liver transplant can provide a tolerogenic benefit to multiorgan transplant recipients. Posttransplant donor-specific antibody (DSA) may be associated with worse outcomes; however, the role for testing DSA in SLKT is unclear.

This study retrospectively assessed the impact of DSA on outcomes following primary SLKT at a large-volume center between 2008 and 2018. Patients were grouped by positive DSA, negative DSA, and DSA not tested, and data were obtained from our institutional database and chart review.

The cohort included 138 SLKT recipients with a mean age of 56.1 ± 9.7 y; 61.6% were male, and 55.8% were Hispanic. Overall, 62 patients were tested for DSA posttransplant, and 33 patients (23.9%) had at least 1 DSA detected. A total of 34 patients (24.6%) experienced at least 1 episode of liver rejection, and 23 patients (16.7%) experienced kidney rejection. Over 50% of patients with de novo DSA changed status during their posttransplant course. Rates of both liver and kidney rejection were slightly higher in the DSA + group, but liver allograft, kidney allograft, and patient survival did not differ when grouped by whether DSA testing was performed or DSA positivity.

These data demonstrate that SLKT is associated with excellent long-term patient and allograft survival with a relatively low rate of rejection. In our experience, testing for DSA does not impact SLKT outcomes' and further multicenter analyses are needed to establish standard of care.

Assessing the survival benefit of transplantation in patients with end-stage liver disease is critical in guiding the decision-making process for liver allocation. Previous studies established increased mortality risk for those transplanted below Model for End-Stage Liver Disease (MELD) 18 compared with candidates who remained on the waitlist; however, improved outcomes of liver transplantation and a changing landscape in the donor supply warrant re-evaluation of this idea.

Using the United Network for Organ Sharing database, we analyzed 160 290 candidates who were waitlisted for liver transplantation within MELD cohorts. We compared patients who were transplanted in a MELD cohort with those listed but not transplanted in that listed MELD cohort with an intent-to-treat analysis.

Those transplanted at a MELD between 6 and 11 showed a 31% reduction in adjusted mortality (HR = 0.69 [95% confidence interval [CI], 0.66-0.75]; P < 0.001) compared with the intent-to-treat cohort in a Cox multivariate regression. This mortality benefit increased to a 37% adjusted reduction for those transplanted at MELD between 12 and 14 (HR = 0.63 [95% CI, 0.60-0.66]; P < 0.001) and a 46% adjusted reduction for those transplanted at a MELD between 15 and 17 (HR = 0.54 [95% CI, 0.52-0.57]; P < 0.001), effects that remained in sensitivity analyses excluding patients with hepatocellular carcinoma, encephalopathy, ascites, and variceal bleeds. A multivariate analysis of patients transplanted at MELD < 18 found younger age and cold ischemia time were protective, whereas older age, lower functional status, and socioeconomic factors increased mortality risk.

These findings challenge the current practice of deferring liver transplants below a particular MELD score by demonstrating survival benefits for most transplant patients at the lowest MELD scores and providing insight into who benefits within these subgroups.

Shortages of liver allografts for children awaiting transplantation have led to high LT waitlist mortality. Prior studies have shown that usage of TVG can reduce waiting time and waitlist mortality, but their use is not universal. We sought to compare patient and graft survival between WLG and TVG and to identify potential associated risk factors in a contemporary pediatric LT cohort.

We performed a retrospective analysis of patient survival, graft survival, and biliary and vascular complications for LT recipients <18 years old entered into the Society of Pediatric Liver Transplantation prospective multicenter database.

Of 1839 LT recipients, 1029 received a WLG and 810 received a TVG from either a LD or a DD. There was no difference in patient survival or graft survival by graft type. Three-year patient survival and graft survival were 96%, 93%, and 96%, and 95%, 89%, and 92% for TVG-LD, TVG-DD, and WLG, respectively. Biliary complications were more frequent in TVG. Hepatic artery thrombosis was more frequent in WLG. Multivariate analysis revealed primary diagnosis was the only significant predictor of patient survival. Predictors for graft survival included time-dependent development of biliary and vascular complications.

There were no significant differences in patient and graft survival based on graft types in this North American multi-center pediatric cohort. Widespread routine use of TVG should be strongly encouraged to decrease mortality on the waitlist for pediatric LT candidates.

Alcohol-related liver disease (ARLD) remains one of the leading causes of chronic liver disease and the prevalence of alcohol-related cirrhosis is still increasing worldwide. Thus, ARLD is one of the leading indications for liver transplantation (LT) worldwide especially after the arrival of direct-acting antivirals for chronic hepatitis C infection. Despite the risk of alcohol relapse, the outcomes of LT for ARLD are as good as for other indications such as hepatocellular carcinoma (HCC), with 1-, 5-, and 10- year survival rates of 85%, 74%, and 59%, respectively. Despite these good results, certain questions concerning LT for ARLD remain unanswered, in particular because of persistent organ shortages. As a result, too many transplantation centers continue to require 6 months of abstinence from alcohol for patients with ARLD before LT to reduce the risk of alcohol relapse even though compelling data show the poor prognostic value of this criterion. A recent pilot study even observed a lower alcohol relapse rate in patients receiving LT after less than 6 months of abstinence as long as addictological follow-up is reinforced. Thus, the question should not be whether LT should be offered to patients with ARLD but how to select patients who will benefit from this treatment.