Xenogeneic cross-circulation for physiological support and recovery of ex vivo human livers.

BACKGROUND AND AIMS: The scarcity of suitable donor livers highlights a continuing need for innovation to recover organs with reversible injuries in liver transplantation. APPROACH AND RESULTS: Explanted human donor livers (n = 5) declined for transplantation were supported using xenogeneic cross-circulation of whole blood between livers and xeno-support swine. Livers and swine were assessed over 24 hours of xeno-support. Livers maintained normal global appearance, uniform perfusion, and preservation of histologic and subcellular architecture. Oxygen consumption increased by 75% ( p = 0.16). Lactate clearance increased from -0.4 ± 15.5% to 31.4 ± 19.0% ( p = 0.02). Blinded histopathologic assessment demonstrated improved injury scores at 24 hours compared with 12 hours. Vascular integrity and vasoconstrictive function were preserved. Bile volume and cholangiocellular viability markers improved for all livers. Biliary structural integrity was maintained. CONCLUSIONS: Xenogeneic cross-circulation provided multisystem physiological regulation of ex vivo human livers that enabled functional rehabilitation, histopathologic recovery, and improvement of viability markers. We envision xenogeneic cross-circulation as a complementary technique to other organ-preservation technologies in the recovery of marginal donor livers or as a research tool in the development of advanced bioengineering and pharmacologic strategies for organ recovery and rehabilitation.

Perioperative Characteristics and Outcomes of Fontan Versus Non-Fontan Patients Undergoing Combined Heart-Liver Transplantation: A Retrospective Cohort Study.

OBJECTIVES: Combined heart-liver transplantation (CHLT) is becoming increasingly frequent as a maturing population of patients with Fontan-palliated congenital heart disease develop advanced liver fibrosis or cirrhosis. The authors present their experience with CHLT for congenital and noncongenital indications, and identify characteristics associated with poor outcomes that may guide intervention in high-risk patients. DESIGN: This was a single-center retrospective cohort study. SETTING: This study was conducted at Vanderbilt University Medical Center in Nashville, Tennessee. PARTICIPANTS: The study included 16 consecutive adult recipients of CHLT at the authors' institution between April 2017 and February 2022. INTERVENTIONS: Eleven patients underwent transplantation for Fontan indications, and 5 were transplanted for non-Fontan indications. MEASUREMENTS AND MAIN RESULTS: Compared with non-Fontan patients, Fontan recipients had longer cardiopulmonary bypass duration (199 v 119 minutes, p =m0.002), operative times (786 v 599 minutes, p = 0.01), and larger blood product transfusions (15.4 v 6.3 L, p = 0.18). Six of 16 patients required extracorporeal membrane oxygenation (ECMO), of whom 4 were Fontan patients who subsequently died. Patients who required ECMO had lower 5-hour lactate clearance (0.0 v 3.5 mmol/L, p = 0.001), higher number of vasoactive infusions, lower pulmonary artery pulsatility indices (0.58 v 1.77, p = 0.03), and higher peak inspiratory pressures (28.0 v 18.5 mmHg, p = 0.01) after liver reperfusion. CONCLUSIONS: Combined heart-liver transplantation in patients with Fontan-associated end-organ disease is particularly challenging and associated with higher recipient morbidity compared with non-Fontan-related CHLT. Early hemodynamic intervention for signs of ventricular dysfunction may improve outcomes in this growing high-risk population.

The Association Between Solid Organ Transplant and Recurrence of Acute Diverticulitis: A National Assessment.

OBJECTIVE: Compare rates and severity of recurrent acute diverticulitis in patients with and without solid organ transplant. SUMMARY BACKGROUND DATA: Immunocompromised solid organ transplant recipients have been considered higher risk for both recurrence and severity of acute diverticulitis. Current guidelines recommend an individualized approach for colectomy in these patients, but these are based on single-center data. METHODS: We identified patients with acute diverticulitis using the Merative MarketScan commercial claims data from 2014-2020. Patients were classified by history of solid organ transplant. The primary outcome was recurrence of acute diverticulitis with an associated antibiotic prescription ≥60 days from the initial episode. Secondary outcomes included hospitalization, colectomy, and ostomy in patients with recurrence. Analyses used inverse probability weighting to adjust for imbalances in covariates. RESULTS: Of 170,697 patients with evidence of acute diverticulitis, 442 (0.2%) had a history of solid organ transplantation. In the weighted cohort, among people who had not been censored at one year (n=515), 112 (22%; 95% CI 20%-25%) experienced a recurrence within the first year. Solid organ transplantation was not significantly associated with a risk of recurrence (HR 1.19; 95% CI 0.94-1.50). There was also no statistically significant difference in the hospitalization rate for recurrent diverticulitis. Restricting the analysis to hospitalized recurrences, there was no statistically significant difference observed in either length of stay or discharge status. CONCLUSIONS: In this national analysis of commercially-insured patients with acute diverticulitis we found no statistically significant differences in recurrence between those with and without a history of solid organ transplant. We do not support an aggressive colectomy strategy based on concern for increased recurrence rate and severity in a solid organ transplant population.

Systematic review and meta-analysis of open versus laparoscopy-assisted versus pure laparoscopic versus robotic living donor hepatectomy.

The value of minimally invasive approaches for living donor hepatectomy remains unclear. Our aim was to compare the donor outcomes after open versus laparoscopy-assisted versus pure laparoscopic versus robotic living donor hepatectomy (OLDH vs. LALDH vs. PLLDH vs. RLDH). A systematic literature review of the MEDLINE, Cochrane Library, Embase, and Scopus databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement (up to December 8, 2021). Random-effects meta-analyses were performed separately for minor and major living donor hepatectomy. The risk of bias in nonrandomized studies was assessed using the Newcastle-Ottawa Scale. A total of 31 studies were included. There was no difference in donor outcomes after OLDH versus LALDH for major hepatectomy. However, PLLDH was associated with decreased estimated blood loss, length of stay (LOS), and overall complications versus OLDH for minor and major hepatectomy, but also with increased operative time for major hepatectomy. PLLDH was associated with decreased LOS versus LALDH for major hepatectomy. RLDH was associated with decreased LOS but with increased operative time versus OLDH for major hepatectomy. The scarcity of studies comparing RLDH versus LALDH/PLLDH did not allow us to meta-analyze donor outcomes for that comparison. There seems to be a marginal benefit in estimated blood loss and/or LOS in favor of PLLDH and RLDH. The complexity of these procedures limits them to transplant centers with high volume and experience. Future studies should investigate self-reported donor experience and the associated economic costs of these approaches.

Six-Year Evaluation of Same-Day Discharge following Conventional Transarterial Chemoembolization of Hepatocellular Carcinoma.

PURPOSE: To evaluate whether same-day discharge increased the incidence of 30-day readmission (30dR) after conventional transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) at a single institution. MATERIALS AND METHODS: In this retrospective study, 253 patients with HCC underwent 521 transarterial chemoembolization procedures between 2013 and 2020. TACE was performed with 50-mg doxorubicin/10-mg mitomycin C/5-10-mL ethiodized oil/particles. Patients not requiring intravenous pain medications were discharged after a 3-hour observation, and 30dR was tracked. The primary objective was to determine the incidence of 30dR in same-day discharge patients versus patients admitted for observation using the chi-square test. Secondary objectives assessed factors associated with overnight admission and factors predictive of 30dR using generalized estimated equation calculations and logistic regression. RESULTS: In the cohort, 24 readmissions occurred within 30 days (4.6%). Same-day discharge was completed after 331 TACE procedures with sixteen 30dRs (4.8%). Patients admitted overnight were readmitted 8 times after 190 TACE procedures (4.2%). This difference was not statistically significant (P = .4). Factors predicting overnight admission included female sex (58/190 [30.5%] vs 58/331 [17.5%], P < .001) and tumor size of ≥3.8 cm (104/190 [55%] vs 85/190 [45%]). Factors predicting 30dR included female sex (10/116 [8.6%] vs 14/405 [0.2%]) and younger age (median [interquartile range], 63 years [55-65 years] vs 65 years [59-71 years]). At regression, factors predictive of 30dR were Child-Pugh Class B/C (odds ratio [OR], 2.1; P = .04) and female sex (OR, 2.9; P = .004). CONCLUSIONS: Same-day discharge after conventional TACE is a safe and effective strategy with 30dR rate of <5%, similar to overnight observation.

Update on combined heart and liver transplantation: evolving patient selection, improving outcomes, and outstanding questions.

PURPOSE OF REVIEW: Combined heart and liver transplantation (CHLT) is an uncommon but increasingly performed procedure with rising need as the population who has undergone Fontan palliation for single ventricle physiology grows. This article reviews the current literature to summarize what is known about patient selection and outcomes and highlights the questions that remain. RECENT FINDINGS: Congenital heart disease (CHD) with Fontan-associated liver disease (FALD) has surpassed noncongenital heart disease as the most common indication for CHLT. In patients with failing Fontan physiology, accurate assessment of recoverability of liver injury remains challenging and requires multifaceted evaluation to determine who would benefit from isolated versus dual organ transplantation. Patient survival has improved over time without significant differences between those with and without a diagnosis of CHD. En bloc surgical technique and best use of intraoperative mechanical circulatory support are topics of interest as the field continues to evolve. SUMMARY: A more refined understanding of appropriate patient selection and indication-specific outcomes will develop as we gain more experience with this complex operation and perform prospective, randomized studies.

A contemporary systematic review on liver transplantation for unresectable liver metastases of colorectal cancer.

The 5-year overall survival rate of a patient with unresectable metastatic colorectal cancer is poor at approximately 14%. Similarly, historical data on liver transplantation (LT) in those with colorectal liver metastases (CRLM) showed poor outcomes, with 5-year survival rates between 12% and 21%. More recently, limited data have shown improved outcomes in select patients with 5-year overall survival rates of approximately 60%. Despite these reported survival improvements, there is no significant improvement in disease-free survival. Given the uncertain benefit with this therapeutic approach and a renewed investigational interest, we aimed to conduct a contemporary systematic review on LT for CRLM. A systematic review of the literature was performed according to the preferred reporting items for systematic reviews and meta-analysis statement. English articles reporting on data regarding LT for CRLM were identified through the MEDLINE (via PubMed), Cochrane Library, and ClinicalTrials.gov databases (last search date: December 16th, 2021) by 2 researchers independently. A total of 58 studies (45 published and 13 ongoing) were included. Although early retrospective studies suggest the possibility that some carefully selected patients may benefit from LT, there is minimal prospective data on the topic and LT remains exploratory in the setting of CRLM. Additionally, several other challenges, such as the limited availability of deceased donor organs and defining appropriate selection criteria, remain when considering the implementation of LT for these patients. Further evidence from ongoing prospective trials is needed to determine if and to what extent there is a role for LT in patients with surgically unresectable CRLM.

Successful liver transplantation in patients with active SARS-CoV-2 infection.

The Coronavirus Disease 2019 (COVID-19) pandemic has substantially impacted solid organ transplantation, including temporary inactivation of waitlist candidates with COVID-19 infection. We report two cases of liver transplantation (LT) in individuals with asymptomatic COVID-19 infection. The first patient is a 68-year-old female with decompensated cirrhosis complicated by worsening frailty and sarcopenia. The second patient is a 22-year-old female with acute liver failure likely secondary to drug/toxin exposure. Both patients were treated with COVID-19-directed therapies and neither patient developed symptomatic disease. These cases demonstrate that LT can be safely performed in select patients with asymptomatic COVID-19 infection at the time of transplant.

Cirrhotic cardiomyopathy: Appraisal of the original and revised criteria in predicting posttransplant cardiac outcomes.

Cardiovascular disease (CVD) significantly contributes to morbidity and mortality after liver transplantation (LT). Cirrhotic cardiomyopathy (CCM) is a risk factor for CVD after transplant. CCM criteria were originally introduced in 2005 with a revision proposed in 2020 reflecting echocardiographic technology advancements. This study assesses the two criteria sets in predicting major adverse cardiac events (MACE) after transplant. This single-center retrospective study reviewed adult LT recipients between January 1, 2009, and December 31, 2018. Patients with insufficient pre-LT echocardiographic data, prior ischemic heart disease, portopulmonary hypertension, or longitudinal care elsewhere were excluded. The primary composite outcome was MACE (arrhythmia, heart failure, cardiac arrest, and/or cardiac death) after transplant. Of 1165 patients, 210 met the eligibility criteria. CCM was present in 162 patients (77%) per the original criteria and 64 patients (30%) per the revised criteria. There were 44 MACE and 31 deaths in the study period. Of the deaths, 38.7% occurred secondary to CVD. CCM defined by the original criteria was not associated with MACE after LT (p = 0.21), but the revised definition was significantly associated with MACE (hazard ratio [HR], 1.93; 95% confidence interval, 1.05-3.56; p = 0.04) on multivariable analysis. Echocardiographic variable analysis demonstrated low septal e' as the most predictive variable for MACE after LT (HR, 3.45; p < 0.001). CCM, only when defined by the revised criteria, was associated with increased risk for MACE after LT, validating the recently revised CCM definition. Abnormal septal e', reflecting impaired relaxation, appears to be the most predictive echocardiographic criterion for MACE after LT.

Predictors of renal recovery in recipients of liver transplant alone who met 2017 simultaneous liver-kidney transplant criteria.

BACKGROUND: Severe renal dysfunction is common among liver transplant (LT) candidates and often prompts simultaneous liver-kidney transplantation (SLKT) consideration. In view of 2017 United Network of Organ Sharing (UNOS) criteria for SLKT, we investigated the likelihood and predictors of renal recovery among patients who met the aforementioned criteria yet received liver transplant alone (LTA). METHODS: We retrospectively analyzed relative renal recovery (RRR; increase in eGFR to >30 ml/min) in adult LTA recipients between 1/2009 and 1/2019. RESULTS: Of 1165 LT recipients, 54 met 2017 UNOS criteria, with 37 receiving LTA. RRR occurred in 84% of LTA recipients, none of whom had pre-LT eGFR <20 ml/min. Sustained RRR (>180 days) occurred in 43% of patients. While prolonged pre-LT severe renal impairment (eGFR <30 ml/min) predicted failure to have sustained RRR (HR .19 per 90-day, CI .04-.87, p < .005), having an eGFR measurement of >30 ml/min within 90 days pre-LT (HR 5.52, CI 1.23-24.79, p .01) associated with achieving sustained RRR. Sustained RRR was protective against the composite outcome of renal replacement therapy, kidney transplant, and death (HR .21, p .01). CONCLUSION: LT candidates who meet 2017 UNOS criteria for SLKT yet undergo LTA can still have relative renal recovery post-LT, exceeding 80% on short-term follow-up and 40% on long-term follow-up. eGFR trends within 90 days pre-LT can predict sustained renal recovery, which appears protective of adverse outcomes. These recovery rates advocate for applying the more restrictive criteria for SLKT outlined in this article and increasing utilization of the safety net (SN) policy for those who do not meet the proposed criteria.

Applicability of the UK DCD risk score in the modern era of liver transplantation: A U.S. update.

BACKGROUND: Careful graft and recipient selection have resulted in improved outcomes in liver transplantation (LT) using donation after cardiac death (DCD) organs. The UK DCD Risk Score was established as a risk stratification tool to guide selection. METHODS: We evaluated the applicability of the UK DCD Risk Score in a contemporary US cohort of adult DCD LT recipients using the United Network for Organ Sharing registry (2011-2020). RESULTS: A total of 3,899 DCD LTs were included in our study (UK DCD Risk Score 0-5 points: 1,438 [36.9%], 6-10 points: 2,034 [52.2%]; 11-20 points: 427 [11.0%]). Compared to a score of 6-10 points, a score of 0-5 points was associated with decreased risk of graft loss (HR = .79, 95%CI: .68-.93, p = .004), while a score of 11-20 points was associated with increased risk of graft loss (HR = 1.26, 95%CI: 1.01-1.56, p = .04). The 5-year graft survival for patients with risk scores of 0-5, 6-10, and 11-20 were 75.9%, 71.8%, and 66.5%, respectively. The C-statistic for the UK DCD Risk Score in our contemporary cohort was .611. CONCLUSIONS: The UK DCD Risk Score demonstrates a more limited ability to differentiate recipient outcomes in the modern era of DCD LT in the US. Acceptable long-term outcomes are achievable for patients stratified to the highest-risk group.

Liver transplant after donation from controlled circulatory death versus brain death: A UNOS database analysis and publication bias adjusted meta-analysis.

BACKGROUND: Donation after circulatory death (DCD) is an increasingly utilized alternative to donation after brain death (DBD) to expand the liver donor pool. We compared the outcomes of liver transplant (LT) after DCD versus DBD. METHODS: A PRISMA-compliant systematic literature review was performed using the PubMed, Cochrane Library, and Embase databases (end-of-search-date: July 2, 2020). US outcomes were analyzed using the UNOS database (February, 2002-September, 2020). Pooled hazard ratios (HR) for patient and graft survival were obtained through random effect meta-analyses and adjusted for publication bias. RESULTS: Thirteen studies reporting on 1426 DCD and 5385 DBD LT recipients were included. 5620 DCD and 87561 DBD LT recipients were analyzed from the UNOS database. Meta-analysis showed increased risk of patient mortality for DCD (HR = 1.36; 95%CI, 1.09-1.70; P = .01; I2  = 53.6%). When adjusted for publication bias, meta-analysis showed no difference in patient survival between DCD and DBD (HR = 1.15; 95%CI, .91-1.45; P = .25; I2  = 61.5%). Meta-analysis showed increased risk of graft loss for DCD (HR = 1.50; 95%CI, 1.20-1.88; P < .001; I2  = 67.8%). When adjusted for publication bias, meta-analysis showed a reduction in effect size (HR = 1.36; 95%CI, 1.06-1.74; P = .02; I2  = 73.5%). CONCLUSION: When adjusted for publication bias, no difference was identified between DCD and DBD regarding patient survival, while DCD was associated with an increased risk of graft loss.

Waitlist mortality and post-liver transplant outcomes of pediatric patients with hepatocellular carcinoma and hepatoblastoma in the United States.

BACKGROUND: Liver transplantation (LT) is offered in cases of advanced disease for both pediatric patients with hepatoblastoma (HBL) and those with hepatocellular carcinoma (HCC). Current United States organ allocation priorities differ between the two groups. METHODS: We retrospectively examined the waitlist and posttransplant outcomes of pediatric LT candidates with HBL and HCC using the United Network for Organ Sharing registry (February 2002 to September 2020). RESULTS: Six hundred sixty-eight children with HBL and 95 children with HCC listed for first LT were identified. Patients with HBL were younger (p < .001), had lower laboratory Model for End-stage Liver Disease (MELD)/Pediatric End-stage Liver Disease (PELD) scores (p < .001), and had lesser proportion with encephalopathy (p = .01). Patients with HCC had an increased risk of waitlist mortality in univariable (unadjusted subdistribution hazard ratio [sHR] = 4.37, 95% confidence interval [CI], 2.01-9.51, p < .001) and multivariable competing risk regression (adjusted sHR = 3.08, 95% CI 1.13-8.37, p = .03) accounting for age and laboratory MELD/PELD score. Five hundred ninety-five children underwent LT for HBL and 76 for HCC. Patients transplanted for HBL had a significantly higher proportion with status 1B exception (71.3% vs. 7.9%, p < .001). No difference was observed in patient (unadjusted log-rank test, p = .52; adjusted hazard ratio [HR] = 0.77, 95% CI, 0.40-1.48, p = .43) or graft survival (unadjusted log-rank test, p = .93; adjusted HR = 0.74, 95% CI 0.42-1.33, p = .32) between HCC and HBL recipients. CONCLUSION: Waitlist mortality for pediatric LT candidates with HCC is significantly higher than for HBL, while posttransplant patient and graft survival are similar. This highlights an opportunity to improve equitable prioritization for children with HCC who may have reduced access to size-appropriate deceased donor organs and less effective bridge-to-transplant therapies.

Pediatric Liver Transplant Survival in Alagille Syndrome Is Comparable to Biliary Atresia-A Linked Database Analysis.

OBJECTIVES: This study aims to report liver transplantation (LT) outcomes and cardiac disease manifestations in children with Alagille Syndrome (ALGS) in a contemporary cohort. METHODS: This project used a novel linkage between the Scientific Registry of Transplant Recipients and Pediatric Health Information System databases. All children ≤21 years undergoing a first LT were identified (2002-2018). The presence of ALGS was identified using Scientific Registry of Transplant Recipients diagnosis coding. Subjects with ALGS were age-matched 1:2 to LT recipients with biliary atresia (BA). The Kaplan-Meier method and log-rank test were used to compare patient and graft survival between groups. RESULTS: A total of 156 LT recipients with ALGS were identified and matched to a control group of 312 LT recipients with BA. Children with ALGS were more likely to have an associated diagnosis of congenital heart disease (80.7% vs 16.4%; P = 0.001) compared with children with BA with 40 (25.6%) children with AGS requiring cardiac intervention (catheter or surgical) either before or after LT. Those patients with ALGS had a higher creatinine, laboratory MELD, and PELD scores before LT. No difference was observed regarding patient or graft survival between children with ALGS and children with BA ( P = 0.08 and P = 0.27, respectively). CONCLUSIONS: Despite increased rate of congenital heart defects and cardiac interventions, higher creatinine, and higher laboratory MELD/PELD scores at time of transplant, this study demonstrates that there is no difference in either patient or graft survival between patients with ALGS and BA.

Liver Transplantation for Langerhans Cell Histiocytosis: A US Population-Based Analysis and Systematic Review of the Literature.

Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder. Liver involvement is seen in 10.1% to 19.8% of patients with LCH and can lead to secondary sclerosing cholangitis requiring liver transplantation (LT). We describe the characteristics and outcomes of patients undergoing LT for LCH. All patients undergoing a first LT for LCH in the United States were identified in the Scientific Registry of Transplant Recipients (SRTR) database (1987-2018). The Kaplan-Meier curve method and log-rank tests evaluated post-LT survival. A systematic literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. A total of 60 LCH LT recipients were identified in the SRTR, and 55 patients (91.7%) were children with median total bilirubin levels at LT of 5.8 mg/dL (interquartile range [IQR], 2.7-12.9). A total of 49 patients (81.7%) underwent deceased donor LT (DDLT). The 1-year, 3-year, and 5-year patient survival rates were 86.6%, 82.4%, and 82.4%, respectively. The systematic review yielded 26 articles reporting on 50 patients. Of the patients, 41 were children (82.0%), 90.0% had multisystem LCH, and most patients underwent DDLT (91.9%; n = 34/37). Pre-LT chemotherapy was administered in 74.0% and steroids in 71.7% (n = 33/46) of the patients, and a recurrence of LCH to the liver was reported in 8.0% of the patients. Of the 50 patients, 11 (22.0%) died during a median follow-up of 25.2 months (IQR, 9.0-51.6), and the 1-year patient survival rate was 79.4%. LT can be considered as a feasible life-saving option for the management of liver failure secondary to LCH in well-selected patients.

Liver Transplantation in Children with Urea Cycle Disorders: The Importance of Minimizing Waiting Time.

Liver transplantation (LT) for children with urea cycle disorders (UCDs) is capable of correcting the enzymatic defect and preventing progressive neurologic injury. We describe the characteristics and outcomes of pediatric LT recipients with UCDs. We identified all pediatric (<18 years) LT candidates with UCDs in the United Network for Organ Sharing (UNOS) database (February 2002 to September 2020). Multivariable Cox and logistic regression were used to determine risk factors for graft loss and cognitive delay, respectively. Of 424 patients, 1.9% (8/424) experienced waitlist mortality and 95.0% underwent LT (403/424). The most frequently encountered UCDs in our cohort were ornithine transcarbamylase deficiency (46.2%), citrullinemia (20.3%), and argininosuccinic aciduria (ASA; 12.9%). The 1-, 3-, and 5-year graft survival rates were 90.4%, 86.3%, and 85.2%, respectively. Multivariable analysis showed a decreased risk of graft loss with increasing weight at LT (adjusted hazard ratio [aHR], 0.96; 95% confidence interval [CI], 0.94-0.99; P = 0.02), male sex (aHR, 0.49; 95% CI, 0.28-0.85; P = 0.01), and ASA diagnosis (aHR, 0.29; 95% CI, 0.09-0.98; P = 0.047), when adjusting for location (intensive care/hospital/home) and graft type (both P ≥ 0.65). In multivariable logistic regression, waitlist time (adjusted odds ratio [aOR], 1.10; 95% CI, 1.02-1.17; P = 0.009) and male sex (aOR, 1.71; 95% CI, 1.02-2.88; P = 0.04) were associated with increased odds of long-term cognitive delay. Waitlist duration is associated with a long-term risk of cognitive delay. Given excellent long-term outcomes, early LT evaluation should be considered in all children with UCDs to prevent progressive neurologic injury and optimize cognitive outcomes.

Mortality Determinants in Children with Biliary Atresia Awaiting Liver Transplantation.

OBJECTIVE: To determine risk factors for waitlist mortality in children with biliary atresia listed for liver transplantation. STUDY DESIGN: There were 2704 children with biliary atresia (<12 years of age) listed for a first liver transplant (2002-2018) in the United Network for Organ Sharing database. Fine-Gray regression models for competing risks analysis (main risk = waitlist mortality/delisting owing to too sick; competing risk = liver transplantation) were implemented to identify risk factors for waitlist mortality. RESULTS: The median waitlist time was 83 days (IQR, 34-191). The cumulative incidence of waitlist mortality was 5.2%. In multivariable analysis (n = 2253), increasing bilirubin level (P < .001), portal vein thrombosis (P = .03), and ventilator dependence (P < .001) at listing were associated with a higher risk, whereas weight ≥10 kg at listing (P = .009) was associated with a lower risk of waitlist mortality. When ascites at listing was included in multivariable analysis (n = 1376), it was associated with a higher risk for the composite outcome (P = .03). Encephalopathy at listing was not associated with waitlist mortality (n = 1376; P = .15). CONCLUSIONS: These parameters can be used to more objectively prioritize children with biliary atresia awaiting liver transplantation and identify children with biliary atresia-related end-stage liver disease at high-risk of mortality.

Liver transplantation for congenital hepatic fibrosis.

Congenital hepatic fibrosis (CHF) is a hereditary fibrocystic disease that can progress to portal hypertension and recurrent cholangitis requiring liver transplantation (LT). It can be associated with renal pathology and need for kidney transplantation (KT). We describe the clinical characteristics and outcomes of patients undergoing liver transplantation alone (LTA) and simultaneous liver-kidney transplantation (SLKT) for CHF using the Unites States Scientific Registry of Transplant Recipients. A total of 197 patients who received LT for CHF between 2002 and 2018 were identified - 87 (44.2%) received SLKT, 110 (55.8%) received LTA. The 1-, 3- and 5-year patient survival were 99.0%, 96.2% and 94.6%. The 1-, 3- and 5-year liver graft survival were 94.9%, 91.1% and 89.6%. No significant differences in patient or liver graft survival were observed between the SLKT and LTA groups, or between paediatric and adult recipients. 53.3% of patients with CHF necessitating LT also have significant renal disease requiring KT. Kidney graft survival for isolated KT prior to LT were poorer compared with KT performed simultaneously or after LT. Both LTA and SLKT for CHF are associated with excellent long-term outcomes in paediatric and adult patients.

Adult Combined Heart-Liver Transplantation: The United States Experience.

Background: We aimed to review the indications and outcomes of adults undergoing combined heart-liver transplantation (CHLT) in the US using national registry data. Methods: Adult (≥18 years) CHLT recipients in the United Network for Organ Sharing database were included (09/1987-09/2020; era 1 = 1989-2000, era 2 = 2001-2010, era 3 = 2011-2020). Survival analysis was conducted by means of Kaplan-Meier method, log-rank test, and Cox regression. Results: We identified 369 adults receiving CHLT between 12/1989-08/2020. The number of adult CHLT recipients (R2 = 0.75, p < 0.001) and centers performing CHLT (R2 = 0.80, p < 0.001) have increased over the study period. The most common cardiac diagnosis in the first two eras was restrictive/infiltrative cardiomyopathy, while the most common in era 3 was congenital heart disease (p = 0.03). The 1-, 3-, and 5-years patient survival was 86.8, 80.1, and 77.9%, respectively. In multivariable analysis, recipient diabetes [adjusted hazard ratio (aHR) = 2.35, 95% CI: 1.23-4.48], CHLT between 1989-2000 compared with 2011-2020 (aHR = 5.00, 95% CI: 1.13-22.26), and sequential-liver first CHLT compared with sequential-heart first CHLT (aHR = 2.44, 95% CI: 1.15-5.18) were associated with increased risk of mortality. Higher left ventricular ejection fraction was associated with decreased risk of mortality (aHR = 0.96, 95% CI: 0.92-0.99). Conclusion: CHLT is being increasingly performed with evolving indications. Excellent outcomes can be achieved with multidisciplinary patient and donor selection and surgical planning.

Fatal hepatic necrosis after nivolumab as a bridge to liver transplant for HCC: Are checkpoint inhibitors safe for the pretransplant patient?

Nivolumab is an immune checkpoint inhibitor (ICI) currently in phase 3 clinical trials for hepatocellular carcinoma. The safety of ICIs in recipients of organ allotransplant is unclear, and several reports of fatal alloimmune injury after posttransplant ICI use have been published. We present the first published case of nivolumab used in the pretransplant setting for HCC resulting in fatal acute hepatic necrosis in the immediate postoperative period from a profound immune reaction likely propagated by nivolumab. Further investigation and significant caution are needed in the evaluation of patients awaiting transplant who are receiving ICI therapy.