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To summarize the current literature with respect to COVID-19 vaccine efficacy patients with end-stage renal disease on dialysis and kidney transplant recipients.Immunosuppressed patients are at greater risk of morbidity and mortality from COVID-19 infection. Patients with ESRD and KTR are immunosuppressed and mount a weaker antibody response to COVID-19 mRNA vaccination, and factors including immunosuppressant medications have been implicated for this weakened response. Third and fourth doses of vaccine doses have been shown to increase seropositivity and antibody production in kidney transplant recipients and patients on dialysis. Retrospective studies have demonstrated decreased mortality in vaccinated, immunosuppressed patients.ESRD and KTR patients have decreased antibody response to COVID-19 vaccines, but third and fourth doses have been shown to increase antibody production. Though a correlate of protection between antibody production and efficacy has yet to be fully established in this subset of the population, all US professional bodies who treat ESRD and KTR patients advocate for full vaccination against SARS-CoV-2 based on the data available. Studies demonstrating decreased mortality in vaccinated patients are promising on efficacy. Importantly, because KTR patients mount a weaker antibody response than ESRD patients, vaccination prior to kidney transplantation is critical.

Background Acute portal vein thrombosis is a major cause of fulminant allograft failure in pediatric liver transplantation. Timely intervention is critical to save the graft and patient. Serial interventional radiologic management of this condition is scarcely reported in the literature. Case Summary A recently transplanted 17-year-old male presented to the emergency department with abdominal pain. Rising liver enzymes prompted discovery of a diffuse portal thrombus, which precipitated fulminant liver failure. The adolescent developed respiratory failure, vasodilatory shock, acute kidney injury, and hepatic encephalopathy, complicating treatment. Multiple interventions attempted to clear the thrombus, including interventional radiologic and medical therapies. Uniquely, a continuous infusion catheter was placed at the thrombosis, delivering local tissue plasminogen activator during a 5-day period. Upon thrombus clearance, the patient made a full recovery with no complications during 12 months of follow-up. Conclusions When used as a component of multidisciplinary management, continuous locally directed tissue plasminogen activator may be a useful tool for clearance of persistent portal vein thrombosis.

BACKGROUND This study aimed to compare trends in use of drug overdose (DO) donors in adult versus pediatric liver transplants and the utilization of split liver transplantation in this donor population. METHODS The United Network for Organ Sharing database was reviewed for deceased donor liver transplants from March 2002 to December 2017. Recipients were categorized by donor mechanism of death. Donor splitting criteria was defined as age 3 times the normal limit, and body mass index ≤ 28 kg/m2. RESULTS Adult liver transplants from DO donors increased from 2% in 2002 to 15% in 2017, while pediatric liver transplants from DO donors only increased from

Dysnatremias are a rare but significant event in liver transplantation. While recipient pre-transplant hypernatremia has been demonstrated to increase post-transplant mortality, the degree of hypernatremia and the impact of its resolution have been less well characterized. Here, we used multivariate Cox regression with a comprehensive list of donor and recipient factors in order to conduct a robust multivariate retrospective database study of 54,311 United Network for Organ Sharing (UNOS) liver transplant patients to analyze the effect of pre-transplant serum sodium on post-transplant mortality, post-transplant length of hospitalization, and post-transplant graft survival. Mortality and graft failure increased in a stepwise fashion with increasing pre-transplant hypernatremia: 145 -150 mEq/L (HR = 1.118 and HR = 1.113), 150-155 mEq/L (HR = 1.324 and HR = 1.306), and > 155 mEq/L (HR = 1.623 and HR = 1.661). Pre-transplant hypo- and hypernatremia also increased length of post-transplant hospitalization: < 125 mEq/L (HR = 1.098), 125-130 mEq/L (HR = 1.060), 145 -150 mEq/L (HR = 1.140), and 150-155 mEq/L (HR = 1.358). Resolution of hypernatremia showed no significant difference in mortality compared with normonatremia, while unresolved hypernatremia significantly increased mortality (HR = 1.254), including a durable long-term increased mortality risk for patients with creatinine < 2 mg/dL and MELD < 25. Pre-transplant hypernatremia serves as a morbid prognostic indicator for post-transplant morbidity and mortality.

Amid a viral pandemic with poorly understood transmissibility and pathogenicity in the pediatric patient, we report the first pediatric liver transplants utilizing allografts from SARS-CoV-2+ donors.We describe the outcomes of two pediatric liver transplant recipients who received organs from SARS-CoV-2 nucleic acid test-positive (NAT+) donors. Data were obtained through the respective electronic medical record system and UNet DonorNet platform.The first donor was a 3-year-old boy succumbing to head trauma. One of four nasopharyngeal (NP) swabs and 1 of 3 bronchoalveolar lavage (BAL) NAT tests demonstrated SARS-CoV-2 infection before organ procurement. The second donor was a 16-month-old boy with cardiopulmonary arrest of unknown etiology. Three NAT tests (2 NP swab/1 BAL) prior to procurement failed to detect SARS-CoV-2. The diagnosis was made when the medical examiner repeated 2 NP swab NATs and an archive plasma NAT, all positive for SARS-CoV-2. Both 2-year-old recipients continue to do well 8 months post-transplant, with excellent graft function and no evidence of SARS-CoV-2 transmission.This is the first report to describe successful pediatric liver transplantation from SARS-CoV-2+ donors. These data reinforce the adult transplant experience and support the judicious use of SARS-CoV-2+ donors for liver transplantation in children. With SARS-CoV-2 becoming endemic, the concern for donor-derived viral transmission must now be weighed against the realized benefit of life-saving transplantation in the pediatric population as we continue to work toward donor pool maximization.

Although lung demand continues to outpace supply, 75% of potential donor lungs are discarded without being transplanted in the United States. To identify the discarded cohorts best suited to alleviate the lung shortage and reduce waitlist mortality, we explored changes in survival over time for five marginal donor definitions: age 60 years, smoking history 20 pack-years, PaOOur retrospective cohort study separated 27 803 lung recipients in the UNOS Database into three 5-year eras by transplant date: 2005-2009, 2010-2014, and 2015-2019. Multivariable Cox proportional hazards regression and Kaplan-Meier analysis with log-rank test were used to compare survival across the eras.Three definitions-low PaOAdvanced donor age, previously the most significant risk factor, has improved to near-benchmark levels, demonstrating the possibility for matching older donors to healthier non-elderly recipients in selected circumstances. Low PaO

Background Children with unresectable hepatocellular carcinoma (HCC) have a poor prognosis and limited treatment options. Transarterial radioembolization (TARE) using Yttrium-90 (Y90) has emerged as a potential bridge therapy to hepatic resection or transplantation for HCC with very limited studies in children. Observations Here we present the clinical course of 2 children successfully treated with TARE Y90 for initially unresectable fibrolamellar HCC (FL-HCC) and bridged to partial hemihepatectomy with >1-year overall survival post-TARE. Conclusion Although there have been prior published reports of pediatric patients with HCC being treated with TARE Y90 and some being able to undergo subsequent orthotopic liver transplantation, this is the first report of pediatric HCC patients treated with TARE Y90 as a bridge to nontransplant resections and going on to have >1-year overall survival.

Objectives There is an 18.9% discard rate among kidney allografts. Here, we aimed to determine predictors of kidney discard and construct an index to identify high-probability discard kidney allografts prior to procurement. Materials and methods A total of 102 246 potential kidney allograft donors from the Organ Procurement and Transplantation Network database were used in this analysis. The cohort was randomized into 2 groups. The training set included 67% of the cohort and was used to derive a predictive index for discard that comprised 21 factors identified by univariate and multivariate logistic regression analysis. The validation set included 33% and was used to internally validate the kidney discard risk index. Results In 77.3% of donors, at least 1 kidney was used for transplant, whereas in 22.7% of donors, both kidneys were discarded. The kidney discard risk index was highly predictive of discard with a C statistic of 0.89 (0.88-0.89). The bottom 10th percentile had a discard rate of 0.73%, whereas the top 10th percentile had a discard rate of 83.65%. The 3 most predictive factors for discard were age, creatinine level, and hepatitis C antibody status. Conclusions We identified 21 factors predictive of discard prior to donor procurement and used these to develop a kidney discard risk index with a C statistic of 0.89.

Imminent death donation (IDD) is described as living organ donation prior to a planned withdrawal of life-sustaining care in an imminently dying patient. Although IDD was ethically justified by United Network for Organ Sharing, the concept remains controversial due to presumed lack of public support. The aim of this study was to evaluate the public's attitudes towards IDD. A cross-sectional survey was conducted of US adults age >18 years (n = 2644). The survey included a case scenario of a patient with a devastating brain injury. Responses were assessed on a 5-point Likert scale. Results showed that 68% - 74% of participants agreed or strongly agreed with IDD when posed as a general question and in relation to the case scenario. Participants were concerned about "recovery after a devastating brain injury" (34%), and that "doctors would not try as hard to save a patient's life" (33%). Only 9% of participants would be less likely to trust the organ donation process. In conclusion, our study demonstrates strong public support for IDD in the case of a patient with a devastating brain injury. Notably, participants were not largely concerned with losing trust in the organ donation process. These results justify policy change towards imminent death donation.

Despite improvements in survival across races in the past 20 years, African Americans have worse liver transplant outcomes after orthotopic liver transplantation (OLT). This study aims at quantifying the change in disparities between African Americans and other races in survival after OLT. We retrospectively analyzed the United Network for Organ Sharing (UNOS) database for patient data for candidates who received a liver transplant between January 1, 2007 and December 31, 2017. Multivariate Cox proportional hazards regression indicated similar decreases in mortality over time for each race with a decrease in mortality for African Americans: 2010-2012 (HR = .930), 2012-2015 (HR = .882), and 2015-2017 (HR = .883) when compared to 2007-2010. Risk of mortality for African Americans compared to Caucasians varied across the 4 eras: 2007-2010 (HR = 1.083), 2010-2012 (HR = 1.090), 2012-2015 (HR = 1.070), and 2015-2017 (HR = 1.125). While African Americans have seen increases in survival in the past decade, a similar increase in survival for other races leaves a significant survival disparity in African Americans.

In pediatric liver transplant recipients, hepatic artery thrombosis and portal vein thrombosis are major causes of acute graft failure and mortality within 30 days of transplantation. There is, however, a strong possibility of graft salvage if flow can be re-established to reduce ischemic injury. The current standard treatment is surgical revascularization, and if unsuccessful, retransplantation. Due to our success in treating these complications with catheter-directed therapies, we sought to summarize and publish the outcomes of all patients who experienced hepatic artery thrombosis or portal vein thrombosis within 30 days of liver transplantation.We conducted a retrospective cohort analysis of 27 pediatric liver transplant recipients who experienced hepatic artery thrombosis (n = 13), portal vein thrombosis (n = 9), or both (n = 5) between September 2012 and March 2021. We collected and tabulated data on the patients and therapies performed to treat them, including success rates, primary and secondary patency, and clinical outcomes.Among these patients, 6 were managed with anticoagulation and relisting for transplant and 21 had a primary revascularization attempt. Surgical recanalization was attempted in 7 patients of which 3 had successful recanalization (43%) and catheter-directed recanalization was attempted in 14 patients with 100% success in re-establishing blood flow to the graft. Additionally, patency was increased, and mortality was decreased in patients treated with catheter-directed recanalization compared to surgical revascularization or anticoagulation alone.This data illustrates the need to further investigate catheter-directed thrombolysis as a potential first-line treatment for postoperative HAT and PVT in pediatric liver transplant recipients.

OBJECTIVES Acute-on-chronic liver failure (ACLF), whereas increasingly well-defined in adults, has been poorly characterized in pediatric patients other than having a poor prognosis. This study aimed to identify ACLF and evaluate prognosis in the American pediatric population. METHODS Modified ACLF definitions (p-CLIF) were applied to 11,300 children listed for liver transplantation from March 2002 through 2017 in the Organ Procurement and Transplantation Network (OPTN) database. RESULTS Pediatric ACLF patients have greater mortality within 90 days from listing (46.6% by p-CLIF) than other types of failure (

Background Independent studies provide evidence that low volume pediatric solid organ transplant centers have inferior outcomes compared to high volume pediatric centers. The study assessed whether patients treated at low volume pediatric centers have access to higher volume pediatric centers, which offer potentially better outcomes. Methods We analyzed center specific data on 467 pediatric solid organ transplant centers in the U.S using the Organ Procurement and Transplantation Network database from 2002 to 2014. The proximities of low volume pediatric centers to high volume pediatric centers were determined using Maptive, a tool based on Google Maps. Results Most low volume pediatric transplant centers focused on transplantation of adults (84% heart, 83% liver, and 93% kidney programs). A majority of low volume pediatric centers (77% for heart, 53% for lung, 68% for liver and 90% for kidney) were within 150 miles of high volume centers. Among all children listed for transplantation, 30.7% were listed in low volume pediatric centers. Most low volume pediatric centers are adult focused and near high volume pediatric centers. Conclusion We need greater scrutiny of outcomes, particularly waitlist outcomes, of low volume pediatric solid organ transplant centers located close to high volume pediatric solid organ transplant centers. Type of Study and Level of Evidence Retrospective Comparative Study, Level III.

The field of liver transplantation has shifted considerably in the MELD era, including changing allocation, immunosuppression, and liver failure etiologies, as well as better supportive therapies. Our aim was to evaluate the predictive accuracy of the MELD score over time. The United Network for Organ Sharing provided de-identified data on 120 156 patients listed for liver transplant from 2002-2016. The ability of the MELD score to predict 90-day mortality was evaluated by a concordance (C-) statistic and corroborated with competing risk analysis. The MELD score's concordance with 90-day mortality has downtrended from 0.80 in 2003 to 0.70 in 2015. While lab MELD scores at listing and transplant climbed in that interval, score at waitlist death remained steady near 35. Listing age increased from 50 to 54 years. HCV-positive status at listing dropped from 33 to 17%. The concordance of MELD and mortality does not differ with age (>60 = 0.73

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

The study of marginal liver transplant outcomes, including post-transplant length of stay (LOS), is necessary for determining the practicality of their use. 50,155 patients who received transplants from 2012 to 2020 were retrospectively analyzed with data from the Scientific Registry of Transplant Recipients database using Kaplan-Meier survival curves and multivariable Cox regression. Six different definitions were used to classify an allograft as being marginal: 90th percentile Donor Risk Index allografts, donation after cardiac death donors, national share donors, donors over 70, donors with >30% macrovesicular steatosis, or 90th percentile Discard Risk Index donors. 24% (n = 12,124) of subjects received marginal allografts. Average LOS was 15.6 days among those who received standard allografts. Among those who received marginal allografts, LOS was found to be highest in those who received 90th percentile Donor Risk Index allografts at 15.6 days, and lowest in those who received donation after cardiac death allografts at 12.7 days. Apart from fatty livers (95% CI 0.86 - 0.98), marginal allografts were not associated with a prolonged LOS. We conclude that accounting for experience and recipient matching, transplant centers may be more aggressive in their use of extended criteria donors with limited fear of increasing LOS and its associated costs. This article is protected by copyright. All rights reserved.

Recent preliminary data report lower serological response to SARS-CoV-2 mRNA vaccines in solid organ transplant (SOT) recipients (1, 2). There are no data on factors associated with lack of serological response in SOT recipients - information that could guide recommendations regarding booster dose and closer follow up. We evaluated the serological response to SARS-CoV-2 vaccination in liver transplant (LT) recipients.

Background The aim of this study was to assess improvements in long-term survival of pediatric patients after liver transplantation by analyzing outcomes in transplant recipients who survived beyond 1 year after transplantation. There has been a marked increase in the 1-year survival of pediatric patients, from 78% in transplant recipients between 1987 and 1990 to 95% in transplant recipients between 2011 and 2017. The long-term outcomes have not seen a similar trend, creating a disparity that warrants analysis. Methods We analyzed 13 753 pediatric patients who survived for 1 year after receiving orthotopic liver transplantation between 1987 and 2017. The study period was divided into six eras. Outcomes were analyzed using the Kaplan-Meier method for time-to-event analysis, and multivariable Cox regression. Results There were no significant gains in long-term outcomes among 1-year survivors over the past three decades. Log-rank tests for equality of survivor functions between each era and 1987-1990 were not statistically significant. Cause of death analysis revealed that although infections caused 20.6% of deaths in patients transplanted between 1987 and 1990, this number dropped to 5.6% in those transplanted between 2011 and 2017 (p = .01). Malignancy caused 10.6% of deaths in 1987-1990 but caused 22.2% of the deaths in 2011-2017 (p = .04). Conclusion Despite the gratifying gains in short-term survival of pediatric patients, 1-year survivors have no significant improvements in long-term survival after undergoing a liver transplantation. Long-term sequelae of immunosuppression, such as malignancy and infection, continue to be the most common causes of death. This study highlights the necessity for better long-term management of immunosuppression.

Background Children with end-stage liver disease and multi-organ failure, previously considered as poor surgical candidates, can now benefit from liver transplantation (LT). They often need prolonged mechanical ventilation (MV) post-LT and may need tracheostomy to advance care. Data on tracheostomy after pediatric LT are lacking. Method Retrospective chart review of children who required tracheostomy in the peri-LT period in a large, freestanding quaternary children's hospital from 2014 to 2019. Results Out of 205 total orthotopic LTs performed in 200 children, 18 (9%) required tracheostomy in the peri-transplant period: 4 (2%) pre-LT and 14 (7%) post-LT. Among those 14 needing tracheostomy post-LT, median age was 9 months [IQR = 7, 14] at LT and 10 months [9, 17] at tracheostomy. Nine (64%) were infants and 12 (85%) were cirrhotic at the time of LT. Seven (50%) were intubated before LT. Median MV days prior to LT was 23 [7, 36]. Eight (57%) patients received perioperative continuous renal replacement therapy (CRRT). The median MV days from LT to tracheostomy was 46 [33, 56]; total MV days from initial intubation to tracheostomy was 57 [37, 66]. Four (28%) children died, of which 3 (21%) died within 1 year of transplant. Total ICU and hospital length of stay were 92 days [I72, 126] and 177 days [115, 212] respectively. Among survivors, 3/10 (30%) required MV at home and 8/10 (80%) were successfully decannulated at 400 median days [283, 584]. Conclusion Tracheostomy though rare after LT remains a feasible option to support and rehabilitate critically ill children who need prolonged MV in the peri-LT period.

Previous studies have shown that infection-related cytokine increase of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF- α) can cause suppression of cytochrome P450 3A4 (CYP3A4) enzymes.1 SARS-CoV-2 infection has been associated with increased cytokine levels which may suggest suppression of CYP3A4 enzymes and downstream interaction with CYP-mediated drug metabolism including calcineurin inhibitors.

The number of patients awaiting heart transplantation (HTx) substantially exceeds the number of donor hearts transplanted each year, yet nearly 65% of eligible donor hearts are discarded rather than transplanted. Deceased organ donors listed within the UNOS Deceased Donor Database between 2010 and 2020 were reviewed. Those greater than 10 years old and consented for heart donation were included and randomly separated into training (n = 48,435) and validation (n = 24,217) cohorts. A discard risk index (DSRI) was created using the results of univariable and multivariable analyses. Discard data were assessed at DSRI value deciles, and stratum-specific likelihood ratio (SSLR) analysis and Kaplan-Meier survival function were used for mortality data. Factors associated with higher DSRI values included donor age > 45, LVEF, HBV-core antibodies, hypertension, and diabetes. The DSRI C-statistic was 0.906 in the training cohort and 0.904 in the validation cohort. The DSRI did not reliably predict 30-day or 1-year mortality after transplantation (C-statistic 0.539 & 0.532, respectively). The factors leading to heart allograft discard are not correlated to the same degree with post-transplant outcomes. This suggests that optimizing utilization of certain allografts with slightly higher risk of discard could increase the heart donor pool with limited impact on posttransplant mortality. This article is protected by copyright. All rights reserved.

BACKGROUND Liver Transplantation has advanced over the past 3 decades, with 1-year survival rates improving 25%. Survival rates for those transplanted has increased to remarkable levels, but survival from the time of listing may not be as revolutionary. METHODS Kaplan-Meier with log-rank test as well as Cox regression analysis was used to retrospectively analyze 211 610 adults listed for LT and 116 299 adult transplant recipients from 1987 to 2016. Our primary endpoints were survival from time of listing to waitlist death or posttransplant death. RESULTS One-year survival following LT improved dramatically (68% in 1987-1988 vs. 93% in 2016, P

Mohamed Saleh Ismail,1,2 Islam Mohamed,1,2 Efstathia Polychronopoulou,3 John A Goss,4 Yong-Fang Kuo,3 Fasiha Kanwal,1 Prasun K Jalal1,4 1Division of Gastroenterology, Baylor College of Medicine, Houston, TX, USA; 2Department of Internal Medicine, Gastroenterology & Hepatology, Ain Shams University, Cairo, Egypt; 3Department of Biostatistics, The University of Texas Medical Branch, Galveston, TX, USA; 4Michael E. DeBakey Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, USACorrespondence: Prasun K JalalDivision of Gastroenterology, Baylor College of Medicine, Baylor Clinic 6620 Main Street, Suite 1450, Houston, TX, 77030, USATel +1 832-355-1424Fax +1 7136102479Email Jalal@bcm.eduBackground/Aims: Several studies have shown improved outcome of liver transplant (LT) recipients with hepatitis C virus (HCV) since the widespread clinical use of interferon-free direct-acting antivirals (IFN-free DAAs). However, the association of IFN-free DAA therapy on tumor characteristics and on the outcome of LT in patients with hepatocellular carcinoma (HCC) has not been studied. We aimed to examine pre-transplant HCC characteristics and post-LT outcomes in the IFN-based DAA treatment and IFN-free DAA treatment eras.Methods: Using the United Network for Organ Sharing/Organ Procurement and Transplantation Network database, we analyzed adults with a diagnosis of HCV and HCC who received LTs from deceased donors from 04/2012 to 12/2017. Cox regression models were used to identify the association between the IFN-based DAA treatment vs IFN-free DAA treatment era and study outcomes (mortality, graft failure, and HCC recurrence at 1 and 3 years).Results: Complete tumor necrosis was significantly higher in the IFN-free DAA treatment era (22.73% vs 18.22%; P < 0.01). No other HCC tumor characteristics differed significantly between the two eras. HCC recurrence rates were similar between the two eras. On multivariate Cox regression analysis, patients who had transplants in the IFN-free DAA treatment era had lower risk of graft failure compared with the IFN-based DAA treatment group (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.25– 0.77; P < 0.01). Patient mortality was lower in the IFN-free DAA treatment era although the difference was not statistically significant (HR, 0.82; 95% CI, 0.60– 1.13; P =0.22).Conclusion: LT recipients in the IFN-free DAA treatment era had significantly higher complete tumor necrosis in explants. Other HCC tumor characteristics were similar between the two eras. Post-LT graft failure at 1 and 3 years significantly decreased in the IFN-free DAA treatment era among patients with HCV and HCC, although patient mortality was not statistically different.Keywords: hepatocellular carcinoma, liver transplantation, hepatitis C virus, direct-acting antiviral

Introduction: The disparity between the number of individuals on the wait list and available liver allografts creates the need for a system that maximizes donor liver utilization and predicts graft failure. Research Question: This study aimed to determine the relationship between donor Gamma-Glutamyl Transferase (GGT), liver discard, and graft failure. Design: Through multivariate analysis from 53 966 deceased liver donors, we adjusted for donor clinical and demographic characteristics and compared donor GGT with allograft discard. We compared donor GGT ranges with graft failure and analyzed data from 47 269 liver recipients. Results: After adjusting for other factors, donor GGT was significantly associated with liver discard, with GGT over 200 U/L being most significant (OR 2.74, CI 2.51-2.99). Donor GGT under 20 U/L was also found to be a protective factor for post-transplant graft failure (HR 0.91, CI 0.83 – 1.00). Conclusion: Going forward, GGT should be included among other characteristics associated with allograft discard considered during the procurement process.

BACKGROUND Despite noted improvements in short-term survival outcomes following orthotopic heart transplantation (OHT), review of the relevant literature suggests little improvement in long-term outcomes for patients surviving beyond 1 year. METHODS All OHT cases performed between 1989 and 2019 within the United Network for Organ Sharing (UNOS) database were reviewed. Adults who underwent isolated OHT were included in a 1-year survival analysis. Those who survived at least 1 year post-transplant were included in a long-term survival analysis. Demographic factors were assessed using Students' t test and chi-square analysis. Survival trends and risk factors were assessed using the Kaplan-Meier and the Cox regression analysis, respectively. RESULTS A total of 53 265 and 46 372 recipients were included in the short-term and long-term cohorts, respectively. In an adjusted analysis, the reference implant era 2014-2019 had significantly better short-term survival outcomes when compared with earlier implant eras: 1989-1993 (HR: 2.92), 1994-1998 (HR: 1.53), 1999-2003 (HR: 1.27), 2004-2008 (HR: 1.11), and 2009-2013 (HR: 1.02). The same trend was recognized for long-term outcomes: 1989-1993 (HR: 1.87), 1994-1998 (HR: 1.27), 1999-2003 (HR: 1.09), and 2004-2008 (HR: 1.03). CONCLUSIONS Despite increases in multiple traditional risk factors, both short-term and long-term survival outcomes have consistently improved over the past 30 years, suggesting other factors are contributing to improved outcomes in recent eras.

Background Successful liver transplantation is dependent on restoration of hepatic arterial (HA) flow. Although uncommon, some native recipient HAs are not suitable or inadequate for anastomosis, thereby necessitating extra-anatomic HA reconstruction. Splenic artery transposition (SAT) is 1 method of HA reconstruction, in which the recipient splenic artery is transposed to reestablish perfusion of the donor liver. Due to the rarity of the technique, literature describing outcomes is limited. In the current report, we describe 3 patients (2 adults, 1 pediatric) who underwent complex upper abdominal surgery before whole-organ deceased donor liver transplantation with SAT. Methods The demographic and patient care information was collected prospectively and subsequently reviewed retrospectively. Given the de-identified nature of the data included, this study was exempt from approval from an ethics board. Results Recipient splenic arteries were dissected from their origin at the celiac trunk, for approximately 3-5 cm to ensure a gentle anterior-cranial curve toward the right upper quadrant, allowing anastomosis to the donor celiac trunk in an end-to-end fashion. Postoperatively, all 3 patients had rapid normalization of liver function tests and brisk HA flow demonstrated by Doppler ultrasound. Longer-term follow-up, ranging from 1 to 3 years, reveals continued patency of the reconstructed HAs and liver function tests within normal limits. Conclusions Our experience points to SAT as a safe and effective technique for extra-anatomic HA reconstruction.

Background The demand for donor lungs continues to outpace the supply, yet nearly 75% of donor lungs intended for lung transplantation are discarded. Methods We reviewed all donation after brain death organ donors listed within the UNOS Deceased Donor Database between 2005 and 2020. Univariable and multivariable analyses were run on the training set (n=69,355) with the primary outcome defined as lung discard, and the results were used to create a discard risk index (DSRI). Discard data was assessed at DSRI value deciles using the validation set (n=34,670), and differences in 1-year mortality were assessed using stratum-specific likelihood ratio (SSLR) analysis. Results Donor factors most associated with higher DSRI values included age > 65, PaO2 400. The DSRI was a reliable predictor of donor discard, with a C-statistic of 0.867 in the training set and 0.871 in the validation set. The DSRI was not a reliable predictor of 30-day, 1-year, 3-year, and 5-year survival following transplantation (C-statistic 0.519-0.530). SSLR analysis resulted in three 1-year mortality strata (SSLR 0.88 in the 1st DSRI value decile, 1.03 in the 2nd-5th, & 1.19 in the 6th-10th). Conclusions The factors leading to lung allograft discard are not the same as those leading to worse recipient outcomes. This suggests that with proper allocation, many of the grafts that are now commonly discarded could be used in the future donor pool with limited impact on mortality.

Background: The Coronavirus 2019 pandemic has posed a particular challenge for transplant programs across the world as little was understood regarding how the virus would affect immunocompromised hosts. In addition it was unclear if race and socioeconomic status affected hospitalization rates. Methods: We describe a cohort of 25 solid organ transplant recipients (SOTR) within a single-center who were subsequently hospitalized for COVID-19 infection. In addition, we compared baseline characteristics of our cohort with all of our transplants from 1/2/2015 until 11/5/2020. Results: Transplant recipients infected with COVID-19 have many comorbidities (96% with hypertension, 60% with heart failure or ischemic heart disease, and 60% with diabetes). Overall SOTR patients frequently presented with AKI (44%), frequently required ICU stay (52%), and frequently required intubation (36%). We discovered a statistically significant racial disparity in COVID-19 infection in minorities within our cohort compared to our baseline transplant recipient population. Conclusion: Transplant recipients tended to have more atypical symptoms such as diarrhea and tolerated a stepwise reduction of immunosuppression. Solid organ transplant recipients - particularly minorities and low income patients-may benefit from additional COVID-19 precautions such as earlier access to vaccination. [ABSTRACT FROM AUTHOR] Copyright of Trends in Transplantation is the property of Publicidad Permanyer SLU and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Pediatric kidney transplant recipients generally have good outcomes post-transplantation. However, the younger age and longer life span after transplantation in the pediatric population make understanding the multifactorial nature of long-term graft survival critical. This investigation analyzes factors associated with 10-year survival to identify areas for improvement in patient care. Kaplan-Meier with log-rank test and univariable and multivariable logistic regression methods were used to retrospectively analyze 7785 kidney transplant recipients under the age of 18 years from January 1, 1998, until March 9, 2008, using United Network for Organ Sharing (UNOS) data. Our end-point was death-censored 10-year graft survival after excluding recipients whose grafts failed within one year of transplant. Recipients aged 5-18 years had lower 10-year graft survival, which worsened as age increased: 5-9 years (OR: 0.66; CI: 0.52-0.83), 10-14 years (OR: 0.43; CI: 0.33-0.55), and 15-18 years (OR: 0.34; CI: 0.26-0.44). Recipient African American ethnicity (OR: 0.67; CI: 0.58-0.78) and Hispanic donor ethnicity (OR: 0.82; CI: 0.72-0.94) had worse outcomes than other donor and recipient ethnicities, as did patients on dialysis at the time of transplant (OR: 0.82; CI: 0.73-0.91). Recipient private insurance status (OR: 1.35; CI: 1.22-1.50) was protective for 10-year graft survival. By establishing the role of age, race, and insurance status on long-term graft survival, we hope to guide clinicians in identifying patients at high risk for graft failure. This study highlights the need for increased allocation of resources and medical care to reduce the disparity in outcomes for certain patient populations.

Of the 600 pediatric candidates added to the liver waiting list annually, 100 will remain waiting while over 100 liver allografts are discarded, often for subjective reasons.We created a risk index to predict discard to better optimize donor supply. We used the UNOS database to retrospectively analyze 17 367 deceased donors (≤18 years old) through univariate and multivariate logistic regression models. Deceased donor clinical characteristics and laboratory values were independent variables with discard being the dependent variable in the analysis. Significant univariate factors (P-value .05) comprised the multivariate analysis. Significant variables from the multivariate analysis were incorporated into the pDSRI, producing a risk score for discard.From 17 potential factors, 11 were identified as significant predictors (P .05) of pediatric liver allograft discard. The most significant risk factors were as follows: DCD; total bilirubin10 mg/dL, and alanine transaminase (ALT) ≥500 IU/L. The pDSRI has a C-statistic of 0.846 for the training set and 0.840 for the validation set.The pDSRI uses 11 significant risk factors, including elevated liver function tests, donor demographics, and donor risk/type to accurately predict risk of pediatric liver allograft discard and serve as a tool that may maximize donor yield.

Background The clinical course of COVID‐19 in pediatric solid organ transplant recipients remains ambiguous. Though preliminary experiences with adult transplant recipients have been published, literature centered on the pediatric population is limited. We herein report a multi‐center, multi‐organ cohort analysis of COVID‐19 positive transplant recipients ≤ 18 years at time of transplant. Methods Data were collected via institutions’ respective electronic medical record systems. Local review boards approved this cross‐institutional study. Results Among 5 transplant centers, 26 patients (62% male) were reviewed with a median age of 8 years. 6 were heart recipients, 8 kidney, 10 liver, and 2 lung. Presenting symptoms included cough (n=12 (46%)), fever (n=9 (35%)), dry/sore throat (n=3 (12%)), rhinorrhea (n=3 (12%)), anosmia (n=2 (8%)), chest pain (n=2 (8%)), diarrhea (n=2 (8%)), dyspnea (n=1 (4%)), and headache (n=1 (4%)). Six patients (23%) were asymptomatic. No patient required supplemental oxygen, intubation, or ECMO. Eight patients (31%) were hospitalized at time of diagnosis, 3 of whom were already admitted for unrelated problems. Post‐transplant immunosuppression was reduced for only 2 patients (8%). All symptomatic patients recovered within 7 days. Conclusions Our multi‐institutional experience suggests the prognoses of pediatric transplant recipients infected with COVID‐19 may mirror those of immunocompetent children, with infrequent hospitalization and minimal treatment, if any, required.

Background We describe the successful pediatric liver transplant for unresectable hepatoblastoma in a 4‐year‐old male with COVID‐19 prior to transplant. The first negative nasopharyngeal (NP) swab was documented one month after initial diagnosis, when SARS‐CoV‐2 antibodies were also detected. The patient was actively listed for liver transplant after completing four blocks of a SIOPEL‐4 based regimen due to his PRETEXT IV disease which remained unresectable. Following three additional negative NP swabs and resolution of symptoms for four weeks, he underwent a whole‐organ pediatric liver transplant. Methods COVID‐19 positivity determined via NP swab SARS‐CoV‐2 real‐time RT‐PCR (Hologic Aptima SARS‐CoV‐2 RT‐PCR assay). IgG and IgM total SARS‐ CoV‐2 antibodies detected by Ortho Clinical Diagnostics VITROS® Immunodiagnostics Products Anti‐SARS‐CoV‐2 Test. Results Patient received standard prednisone and tacrolimus‐based immunosuppression without induction therapy following transplant. Post‐transplant course was remarkable for neutropenia and thrombocytopenia, with discharge home on post‐transplant day #11. Surveillance tests have remained negative with persistent SARS‐CoV‐2 IgG antibodies at six weeks after transplant. Conclusions We describe one of the earliest, if not the first case of liver transplant following recent recovery from COVID‐19 in a pediatric patient with a lethal malignant liver tumor. A better understanding of how to balance the risk profile of transplant in the setting of COVID‐19 with disease progression if transplant is not performed is needed. We followed existing ASTS guidelines to document clearance of the viral infection and resolution of symptoms before transplant. This case highlights that pediatric liver transplantation can be safely performed upon clearance of COVID‐19.

IMPORTANCE: With continuing improvements in medical devices and more than a decade since the 2006 United Network for Organ Sharing (UNOS) allocation policy, it is pertinent to assess survival among patients on the heart transplantation waiting list, especially given the recently approved 2018 UNOS allocation policy. OBJECTIVES: To assess survival outcomes among patients on the heart transplant waiting list during the past 3 decades and to examine the association of ventricular assist devices (VADs) and the 2006 UNOS allocation policy with survival. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cross-sectional used the UNOS database to perform an analysis of 95 323 candidates wait-listed for heart transplantation between January 1, 1987, and December 29, 2017. Candidates for all types of combined transplants were excluded (n = 2087). Patients were followed up from the time of listing to death, transplantation, or removal from the list due to clinical improvement. Competing-risk, Kaplan-Meier, and multivariable Cox proportional hazards regression analyses were used. MAIN OUTCOMES AND MEASURES: The analysis involved an unadjusted and adjusted survival analysis in which the primary outcome was death on the waiting list. Because of changing waiting list preferences and policies during the study period, the intrinsic risk of death for wait-listed candidates was assessed by individually analyzing, comparing, and adjusting for several candidate risk factors. RESULTS: In total, 95 323 candidates (72 915 men [76.5%]; mean [SD] age, 51.9 [12.0] years) were studied. In the setting of changes in listing preferences, 1-year survival on the waiting list increased from 34.1% in 1987-1990 to 67.8% in 2011-2017 (difference in proportions, 0.34%; 95% CI, 0.32%-0.36%; P

Background PELD scores are used to reduce waitlist mortality, but they do not accurately predict likelihood of prolonged length-of-stay or higher costs associated with it. This study aims to create a pediatric length-of-stay (LOS) index to predict increased risk of prolonged stay following liver transplantation. Methods The scoring system generated predicts length-of-stay following pediatric liver transplantation. With univariate and multivariate analyses on data from 5669 pediatric liver transplant recipients, independent recipient/donor risk factors for prolonged stay (>30 days) were identified. Multiple imputations accounted for missing variables. Results The most significant factors were ICU admission (OR 2.92, CI 2.27-3.75), recipient bilirubin >32 (OR 2.35, CI 1.70-3.25), and hemodialysis 1 week before transplantation (OR 2.27, CI 1.57-3.27). The LOS index assigns weighted scoring points to factors to predict prolonged stay (C-statistic of .72). The index demonstrated discrimination across the population after dividing it into quartiles for prolonged stay. Conclusions The pediatric LOS index, utilizing 13 donor/recipient factors, can assess the risk for pediatric liver transplantation prolonged stay. Important predictive factors are hemodialysis, ICU admission, recipient weight and bilirubin, and recipient life support status.

Background Aggressive acceptance of liver allografts has driven utilization of marginal allografts. Our aim was to assess the impact of the aggressive phenotype on transplant center outcomes over time. Methods We used a cohort of 148 361 candidates from the Organ Procurement and Transplantation Network for liver transplantation between 2002 and 2016 in 134 centers. Using the Discard Risk Index, we designated high probability discard allografts by the top 10th percentile for likelihood of discard. Aggressive phenotype was defined by usage of high probability discard (HPD) allografts (top 10th percentile). Our analysis of survival on waitlist and graft survival after transplantation included a comprehensive list of center level covariates across three equal time periods (2002-2006, 2007-2011, and 2012-2016). Results After adjusting for recipient and center-level factors, aggressive centers had improving graft survival over time. Aggressive vs non-aggressive centers: 2002-2006 HR 1.12 (1.05-1.19), 2007-2011 HR 1.13 (1.05-1.22), 2012-2016 HR 0.99 (0.89-1.10). Aggressive centers had improved waitlist survival compared with non-aggressive centers after adjusting for allograft disparity. Conclusions Aggressive phenotype had a positive impact on waitlist survival, and graft survival in aggressive centers have improved to benchmark levels over time. These findings serve as justification for aggressive utilization of allografts.

Background Organic acidemias, especially propionic acidemia (PA) and methylmalonic acidemia (MMA), may manifest clinically within the first few hours to days of life. The classic presentation in the newborn period includes metabolic acidosis, hyperlactatemia, and hyperammonemia that is precipitated by unrestricted protein intake. Implementation of newborn screening to diagnose and initiate early treatment has facilitated a reduction in neonatal mortality and improved survival. Despite early diagnosis and appropriate management, these individuals are prone to have recurrent episodes of metabolic acidosis and hyperammonemia resulting in frequent hospitalizations. Liver transplantation (LT) has been proposed as a treatment modality to reduce metabolic decompensations which are not controlled by medical management. Published reports on the outcome of LT show heterogeneous results regarding clinical and biochemical features in the post transplantation period. As a result, we evaluated the outcomes of LT in our institution and compared it to the previously published data. Study design/methods We performed a retrospective chart review of nine individuals with PA or MMA who underwent LT and two individuals with MMA who underwent LT and kidney transplantation (KT). Data including number of hospitalizations, laboratory measures, cardiac and neurological outcomes, dietary protein intake, and growth parameters were collected. Results The median age of transplantation for subjects with MMA was 7.2 years with a median follow up of 4.3 years. The median age of transplantation for subjects with PA was 1.9 years with a median follow up of 5.4 years. The survival rate at 1 year and 5 years post-LT was 100%. Most of our subjects did not have any episodes of hyperammonemia or pancreatitis post-LT. There was significant reduction in plasma glycine post-LT. One subject developed mild elevation in ammonia post-LT on an unrestricted protein diet, suggesting that protein restriction may be indicated even after LT. Conclusion In a large single center study of LT in MMA and PA, we show that LT may reduce the incidence of metabolic decompensation. Moreover, our data suggest that LT may be associated with reduced number of hospitalizations and improved linear growth in individuals with PA and MMA.

Background Alagille Syndrome (AGS) and Progressive Familial Intrahepatic Cholestasis (PFIC) are rare pediatric biliary disorders that lead to progressive liver disease. This study reviews our experience with the surgical management of these disorders over the last 20 years. Methods We retrospectively reviewed the records of children diagnosed with AGS or PFIC from January 1996 to December 2016. Data collected included demographics, surgical intervention (liver transplant or biliary diversion), and complications. Results Of 37 patients identified with these disorders, 17 patients (8 AGS,9 PFIC) underwent surgical intervention. Mean postsurgical follow-up was 6.9 ± 4.7 years. Liver transplantation was the most common procedure (n = 14). Two patients who were initially thought to have biliary atresia underwent hepatoportoenterostomy, but were subsequently shown to have Alagille syndrome. Biliary diversion procedures were performed in 3 patients (external n = 1, internal n = 2). PFIC patients tended to be older at the time of liver transplant compared to AGS (4.3 ± 3.9 years vs. 2.4 ± 1.1 years, p = 0.25). The AGS patient with external diversion had resolution of symptoms and no complications (follow-up: 12.5 years). Both PFIC patients with internal diversion (conduit between gallbladder and transverse colon) had resolution of pruritus and no progression of liver disease (follow-up: 3.8 and 4.5 years). Conclusions AGS and PFIC are rare biliary disorders in children which result in pruritus and progressive liver failure. Three patients in this series (8%) benefited from biliary diversion for control of pruritus and have not to date required transplantation for progressive liver disease. 38% underwent transplantation owing to pruritus and severe liver dysfunction. Level of Evidence 2b

The application of nontargeted metabolomic profiling has recently become a powerful noninvasive tool to discover new clinical biomarkers. This study aimed to identify metabolic pathways that could be exploited for prognostic and therapeutic purposes in hepatorenal dysfunction in cirrhosis. One hundred three subjects with cirrhosis had glomerular filtration rate (GFR) measured using iothalamate plasma clearance, and were followed until death, transplantation, or the last encounter. Concomitantly, plasma metabolomic profiling was performed using ultrahigh performance liquid chromatography-tandem mass spectrometry to identify preliminary metabolomic biomarker candidates. Among the 1028 metabolites identified, 34 were significantly increased in subjects with high liver and kidney disease severity compared with those with low liver and kidney disease severity. The highest average fold-change (2.39) was for 4-acetamidobutanoate. Metabolite-based enriched pathways were significantly associated with the identified metabolomic signature (P values ranged from 2.07E-06 to 0.02919). Ascorbate and aldarate metabolism, methylation, and glucuronidation were among the most significant protein-based enriched pathways associated with this metabolomic signature (P values ranged from 1.09E-18 to 7.61E-05). Erythronate had the highest association with measured GFR (R-square = 0.571, P 0.0001). Erythronate (R = 0.594, P 0.0001) and N6-carbamoylthreonyladenosine (R = 0.591, P 0.0001) showed stronger associations with measured GFR compared with creatinine (R = 0.588, P 0.0001) even after controlling for age, gender, and race. The 5 most significant metabolites that predicted mortality independent of kidney disease and demographics were S-adenosylhomocysteine (P = 0.0003), glucuronate (P = 0.0006), trans-aconitate (P = 0.0018), 3-ureidopropionate (P = 0.0021), and 3-(4-hydroxyphenyl)lactate (P = 0.0047). A unique metabolomic signature associated with hepatorenal dysfunction in cirrhosis was identified for further investigations that provide potentially important mechanistic insights into cirrhosis-altered metabolism.

Cystic fibrosis liver disease (CFLD) has long been postulated to be secondary to dysfunctional cystic fibrosis transmembrane conductance regulator in the apical biliary epithelium, leading to bile stasis and eventually cirrhosis with portal hypertension. However, pathologic changes in the cystic fibrosis (CF) liver are distinct from the pancreas and lungs in that fibrocystic changes are absent.1,2 Furthermore, the lack of clinically evident biliary obstruction and liver dysfunction suggest there may be alternative mechanisms that contribute to CFLD. Two recent studies in young adults described obliterative portal venopathy (OPV) and noncirrhotic portal hypertension (NCPH) as the predominant pathophysiology in young adults (median, 22 y) with CFLD.3,4 It is unknown if OPV develops early in childhood. Herein, we report the clinical features and liver pathology in 17 explants from children and adolescents with CF, representing 13.6% (17 of 125) of the CF liver transplant population in the United States according to the United Network for Organ Sharing and Organ Procurement and Transplantation Network.

This study uses DNA sequencing to trace a donor organ transplant–mediated cancer transmission and illustrates how precise molecular pathology profiles might reduce future risk for transplant recipients., Four organ transplant recipients from an organ donor diagnosed with anaplastic pleomorphic xanthoastrocytoma developed fatal malignancies for which the origin could not be confirmed by standard methods. We identified the somatic mutational profiles of the neoplasms using next-generation sequencing technologies and tracked the relationship between the different samples. The data were consistent with the presence of an aggressive clonal entity in the donor and the subsequent proliferation of descendent tumors in each recipient. Deleterious mutations in BRAF, PIK3CA, SDHC, DDR2, and FANCD2, and a chromosomal deletion spanning the CDKN2A/B genes, were shared between the recipients’ lesions. In addition to demonstrating that DNA sequencing tracked a donor/recipient cancer transmission, this study established that the genetic profile of a donor tumor and its potential aggressive phenotype could have been determined before transplantation was considered. As the genetic correlates of tumor invasion and metastases become better known, adding genetic profiling by DNA sequencing to the data considered for transplant safety should be considered.

Low case volume has been associated with poor outcomes in a wide spectrum of procedures. Our objective was to study the association of low case volume and worse outcomes in pediatric heart transplant centers, taking the novel approach of including waitlist outcomes in the analysis. We studied a cohort of 6482 candidates listed in the Organ Procurement and Transplantation Network for pediatric heart transplantation between 2002 and 2014; 4665 (72%) of the candidates underwent transplantation. Candidates were divided into groups according to the average annual transplantation volume of the listing center during the study period: more than 10, six to 10, three to five, or fewer than three transplantations. We used multivariate Cox regression analysis to identify independent risk factors for waitlist and posttransplantation mortality. Of the 6482 candidates, 24% were listed in low-volume centers (fewer than three annual transplantations). Of these listed candidates in low-volume centers, only 36% received a transplant versus 89% in high-volume centers (more than 10 annual transplantations) (p < 0.001). Listing at a low-volume center was the most significant risk factor for waitlist death (hazard ratio [HR] 4.5, 95% confidence interval [CI] 3.5-5.7 in multivariate Cox regression and HR 5.6, CI 4.4-7.3 in multivariate competing risk regression) and was significant for posttransplantation death (HR 1.27, 95% CI 1.0-1.6 in multivariate Cox regression). During the study period, one-fourth of pediatric transplant candidates were listed in low-volume transplant centers. These children had a limited transplantation rate and a much greater risk of dying while on the waitlist.

Background Advances in critical care prolong survival in children with liver failure, allowing more critically ill children to undergo orthotopic liver transplantation (OLT). In order to justify the use of a scarce donor resource and avoid futile transplants, we sought to determine survival in children who undergo OLT while receiving pre-OLT critical care. Study Design We analyzed 13,723 pediatric OLTs using the United Network for Organ Sharing (UNOS) database from 1987 to 2015, including 6,746 recipients in the Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease (MELD/PELD) era (2002 to 2015). There were 1,816 recipients (26.9%) admitted to the ICU at the time of transplantation. We also analyzed 354 pediatric OLT recipients at our center from 2002 to 2015, one of the largest institutional experiences. Sixty-five recipients (18.3%) were admitted to the ICU at the time of transplantation. Kaplan-Meier, volume threshold, and multivariable analyses were performed. Results Patient survival improved steadily over the study period, (66% 1-year survival in 1987 vs 92% in 2015; p Conclusions This analysis demonstrates that the use of advanced critical care in children and infants with liver failure is justified because OLT can be performed on the sickest children and acceptable outcomes achieved. It is an appropriate use of a scarce donor allograft in a child who would otherwise succumb to a terminal liver disease.

Pediatric liver transplantation has experienced improved outcomes over the last 50 years. This can be attributed in part to establishing optimal use of immunosuppressive agents to achieve a balance between minimizing the risks of allograft rejection and infection. The management of immunosuppression in children is generally more complex and can be challenging when compared with the use of these agents in adult liver transplant patients. Physiologic differences in children alter the pharmacokinetics of immunosuppressive agents, which affects absorption, distribution, metabolism, and drug excretion. Children also have a longer expected period of exposure to immunosuppression, which can impact growth, risk of infection (bacterial, viral, and fungal), carcinogenesis, and likelihood of nonadherence. This review discusses immunosuppressive options for pediatric liver transplant recipients and the unique issues that must be addressed when managing this population. Further advances in the field of tolerance and accommodation are needed to relieve the acute and cumulative burden of chronic immunosuppression in children. Liver Transplantation 23 244-256 2017 AASLD.