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.

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.

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.

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.

Pancreatic adenocarcinoma in liver transplant recipients: a case series.

BACKGROUND: Malignancy is one of the known leading causes of death among long-term liver transplantation (LT) survivors. Pancreatic cancer has an incidence of 7.6/100,000 in North America and constitutes a diagnostic challenge post-LT. METHODS: This is a single-center, retrospective review of the electronic health records (EHRs) of LT recipients with pancreatic adenocarcinoma (1990-2019). The prevalence of pancreatic adenocarcinoma in our institutional non-LT population was assessed using an institutional de-identified database (Synthetic Derivative). RESULTS: Six out of 2,232 (0.27%) LT recipients were diagnosed with pancreatic adenocarcinoma. Median age at diagnosis was 66.0 years (IQR, 57.8-71.8 years). Median time from LT to pancreatic adenocarcinoma diagnosis was 8.9 years (IQR, 4.7-16.2 years), the median size on imaging was 3.2 cm (IQR, 3.1-4.7 cm), and all tumors were located on the head of the pancreas. Three patients underwent surgical resection (one with adjuvant chemotherapy), two underwent palliative care, and one palliative chemotherapy with gemcitabine and abraxane. Over a median follow-up of 220.5 days (IQR, 144.8-399.5 days), all six patients died due to disease progression (100%). Pancreatic adenocarcinoma was diagnosed in 5,033 out of 2,484,772 (0.20%) individuals in the Synthetic Derivative. CONCLUSIONS: Our findings identified an increased incidence of pancreatic adenocarcinoma following LT compared to the general population.

Liver Transplantation for Cholangiocarcinoma: Charting a Path With Lessons Learned From Center Experience.

BACKGROUND: While liver transplantation (LT) with neoadjuvant chemoradiation is increasingly utilized for the management of unresectable cholangiocarcinoma (CCA), data on post-LT survival are limited. METHODS: We identified 844 patients who underwent LT (2002-2019) for nonincidental (CCA listing) or incidental (CCA on explant, not at listing) CCA in the Scientific Registry of Transplant Recipients. Kaplan-Meier and multivariable proportional hazards regression methods evaluated the effects of patient characteristics, donor type, transplant era (before/after 2010), and center volume (center-level CCALTs/active year) on the risk of graft failure and patient mortality. RESULTS: One center performed >12 CCALTs/y, and the rest performed ≤4. Five-year graft survival was 50.6%. Multivariable models demonstrated laboratory model of end-stage liver disease ≥40 versus <15 and center volumes of 1, >1 to ≤2, and >2 to ≤4 CCALTs/y compared to >12 were associated with increased risk of graft failure and mortality (all P ≤ 0.002). Extra vessel use was associated with center volume. Among all recipients, extra vessel use occurred in 55.4% of CCALTs performed at the highest volume center and in 14.0% of cases at centers having ≤4 CCAs/y (P < 0.05). CONCLUSIONS: Center volume-related differences in outcomes and extra vessel use highlight the importance of establishing a unified, effective treatment protocol and the potential utility of regionalization of LT for CCA.

Comparison of Survival Outcomes After Deceased Donor Split Versus Whole Liver Transplant for Hepatocellular Carcinoma.

OBJECTIVES: To mitigate waiting time forlivertransplant for hepatocellular carcinoma, partial or split liver transplant has been utilized. There was concern that regeneration of these grafts would negatively affect oncologic outcomes. MATERIALS AND METHODS: We compared posttransplant graft survival between hepatocellular carcinoma whole livertransplant and partial/splitlivertransplant using Scientific Registry of Transplant Recipients data (2002-2017). The 330 partial/split liver transplant recipients were compared with a logistic regressionbased propensity score 1:1 matched whole liver transplant cohort (n = 330) and a random unmatched whole livertransplant cohort(n = 4143). Kaplan-Meier and multivariable Cox regression models evaluated the effects of partial/split and whole liver transplant on survival. RESULTS: Unadjusted analysis demonstrated no difference in graft survivalbetween thepartial/split and whole liver transplant cohorts (overall log-rank P = .78). After adjustments for recipient age, last laboratory Modelfor End-stage LiverDisease score, hepatitisBviral infection co-diagnosis, liver donor risk index, donor historyofdiabetes, anddonorbodymass index category were made (all P ⟨ .05), multivariable analysis demonstrated no statistically significant difference in the risk of graftfailure in thepartial/splitlivertransplant cohort compared with either the matched or random whole livertransplant cohort (both P ≥ .23). CONCLUSIONS: Partial/split liver transplant was not an independent risk factor for graft failure. Additional studies are needed to further elucidate differences in these populations to determine the "right" candidate for partial/split liver transplant.

Surgical resection and survival outcomes in metastatic young adult colorectal cancer patients.

BACKGROUND: The incidence of colorectal cancer in adults younger than age 50 has increased with rates expected to continue to increase over the next decade. The objective of this study is to examine the survival benefit of surgical resection (primary and/or metastatic) versus palliative therapy in this patient population. METHODS: We identified 6708 young adults aged 18-45 years diagnosed with metastatic colorectal cancer (mCRC) from 2004 to 2015 from the SEER database. Overall survival (OS) was analyzed using Kaplan-Meier estimation, log rank test, and multivariate Cox proportional hazards model. RESULTS: Sixty-three percent of patients in our study underwent primary tumor resection (PTR), with 40% undergoing PTR alone and 23% undergoing both resection of primary disease and metastasectomy. The median OS for patients who underwent both PTR and metastasectomy was 36 months, compared to 13 months for those who did not receive any surgical intervention. The multivariate analysis showed significant OS benefit of receiving both PTR and metastasectomy (HR 0.34, 95% CI: 0.31-0.37, p < 0.001) compared to palliative therapy. Undergoing PTR only and metastasectomy only were also associated with improved OS (HR 0.46, 95% CI: 0.43-0.49, p < 0.001 and HR 0.64, 95% CI: 0.55-0.76, p < 0.001, respectively). CONCLUSION: This is the largest observational study to evaluate survival outcomes in young-onset mCRC patients and the role of surgical intervention of the primary and/or metastatic site. Our study provides evidence of statistically significant increase in OS for young mCRC patients who undergo surgical intervention of the primary and/or metastatic site.

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.

Laparoscopic versus open hepatectomy for intrahepatic cholangiocarcinoma: An individual patient data survival meta-analysis.

BACKGROUND: We compared the outcomes of laparoscopic hepatectomy (LH) vs. open hepatectomy (OH) for intrahepatic cholangiocarcinoma (iCCA). METHODS: A systematic review of the MEDLINE, EMBASE, Scopus, and Cochrane Library databases was performed using PRISMA guidelines (end-of-search date: 08-June-2020). Individual patient data on overall survival (OS) and recurrence-free survival (RFS) were extracted. Random-effects meta-analyses, and one- and two-stage survival analyses were conducted. RESULTS: Eight retrospective cohort studies comparing LH (n = 544) vs. OH (n = 2256) were identified. LH demonstrated lower overall complication (Risk ratio [RR] = 0.64, 95% confidence interval [CI]: 0.46-0.90; p = 0.01), surgical lymphadenectomy (RR = 0.74, 95% CI: 0.58-0.93; p = 0.01) and margin-positive resection (RR = 0.78, 95% CI: 0.62-0.99; p = 0.04) rates, and higher recurrence-free rate (RR = 1.24, 95% CI: 1.01-1.51; p = 0.04) vs. OH. In Cox regression, no difference was observed regarding OS (Hazard Ratio [HR] = 1.11, 95% CI: 0.65-1.91; p = 0.70) and RFS (HR = 1.19, 95% CI: 0.74-1.90; p = 0.47). CONCLUSION: The use of LH should be considered when feasible in well-selected iCCA patients by hepatobiliary surgeons with experience in minimally-invasive surgery.

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.

Effect of Donor Transaminase Levels on Graft Survival Following Liver Transplant: An Analysis of the Organ Procurement and Transplantation Network Database.

OBJECTIVES: Despite data showing equivalent outcomes between grafts from marginal versus standard criteria deceased liver donors, elevated donor transaminases constitute a frequent reason to decline potential livers. We assessed the effect of donor transaminase levels and other characteristics on graft survival. MATERIALS AND METHODS: We performed a retrospective cohort analysis of adult first deceased donor liver transplant recipients with available transaminase levels registered in the Organ Procurement and Transplantation Network database (2008-2018). We used Cox proportional hazards regression to determine the effects of donor characteristics on graft survival. RESULTS: Of 53 913 liver transplants, 52 158 were allografts from donors with low transaminases (≤ 500 U/L; group A) and 1755 were from donors with elevated transaminases (> 500 U/L; group B). Group A recipients were more likely to be hospitalized (P = .01) or in intensive care (P < .001) or to have mechanical assistance (P < .001), portal vein thrombosis (P = .01), diabetes mellitus (P = .003), or dialysis the week before liver transplant (P = .004). Multivariable analysis (controlling for recipient characteristics) showed donor risk factors of graft failure included diabetes mellitus (P < .001), donation after cardiac death (P < .001), total bilirubin > 3.5 mg/dL (P < .001), serum creatinine > 1.5 mg/dL (P = .01), and cold ischemia time > 6 hours (P < .001). Regional organ sharing showed lower risk of graft failure (P = .02). Donor transaminases > 500 U/L were not associated with graft failure (relative risk, 1.02; 95% CI, 0.91-1.14; P = .74). CONCLUSIONS: Donor transaminases > 500 U/L should not preclude the use of liver grafts. Instead, donor total bilirubin > 3.5 mg/dL and serum creatinine > 1.5 mg/dL appear to be associated with higher likelihood of graft failure after liver transplant.

Management of hepatoblastoma in the United States: Can we do better?

BACKGROUND: Hepatoblastoma is the most common type of liver cancer in children. Refined therapeutic approaches combining risk-adapted chemotherapy along with complete tumor resection has led to improved survival. We aimed to evaluate the current state of management and outcomes for hepatoblastoma in the United States. METHODS: We retrospectively reviewed 794 children (<18 years) with hepatoblastoma from the National Cancer Database (2004-2015). We assessed overall survival by means of Kaplan-Meier method, log-rank tests, and multivariable Cox regression. RESULTS: Median age was 1 year (interquartile range: 0-2) and 170 (21.4%) presented with metastatic disease. Surgical resection was included in the treatment of 614 (77.3%) children (resection in 66.8% and liver transplantation in 10.6%). In the entire cohort, 95.1% of children received chemotherapy. In the surgical cohort, 575 (93.6%) received chemotherapy (34.5% neoadjuvant, 28.7% adjuvant, 30.5% both neoadjuvant and adjuvant). The 5-year overall survival was 76.6% for the entire cohort (no-surgery group: 55.3% vs surgery group: 82.8%). In multivariable analysis for all children, age ≥8 years (P = .009), metastasis (P < .001), surgery only (P = .009), and chemotherapy only (P < .001) were risk factors for mortality. In multivariable analysis for the surgical cohort, metastasis (P = .001), multifocality (P = .02), no chemotherapy (P = .03), and margin-positive resection (P = .02) were risk factors for mortality. CONCLUSION: Excellent long-term overall survival is achievable with a combination of chemotherapy and surgical resection when a negative resection margin is achieved. However, nearly a quarter of children never received surgical treatment, representing a potential opportunity for improvement in care.

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 for Intrahepatic Cholangiocarcinoma: A Meta-analysis and Meta-regression of Survival Rates.

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is a contraindication to liver transplantation in most centers worldwide. Therefore, only a few such cases have been performed in each individual center, and the need for a systematic review and meta-analysis to cumulatively pool these results is apparent. METHODS: A systematic literature review was conducted using the MEDLINE and Cochrane Library databases according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement (end-of-search date: May 29, 2020). Meta-analyses of proportions were conducted to pool the overall survival (OS), recurrence-free survival (RFS), and overall recurrence rates using the random-effects model. Meta-regression was used to examine cirrhosis and incidental diagnosis as confounders on OS and RFS. RESULTS: Eighteen studies comprising 355 patients and a registry study of 385 patients were included. The pooled 1-, 3-, and 5-y OS rates were 75% (95% CI, 64%-84%), 56% (95% CI, 46%-67%), and 42% (95% CI, 29%-55%), respectively. The pooled 1-, 3-, and 5-y RFS rates were 70% (95% CI, 63%-75%), 49% (95% CI, 41%-57%), and 38% (95% CI, 27%-50%), respectively. Cirrhosis was positively associated with RFS, while incidental diagnosis was not. Neither cirrhosis nor incidental diagnosis was associated with OS. The pooled overall recurrence rate was 43% (95% CI, 33%-53%) over a mean follow-up of 40.6 ± 37.7 mo. Patients with very early (single ≤2 cm) iCCA exhibited superior pooled 5-y RFS (67%; 95% CI, 47%-86%) versus advanced iCCA (34%; 95% CI, 23%-46%). CONCLUSIONS: Cirrhotics with very early iCCA or carefully selected patients with advanced iCCA after neoadjuvant therapy may benefit from liver transplantation under research protocols.

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.

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.

Surgical management of pediatric hepatocellular carcinoma: An analysis of the National Cancer Database.

PURPOSE: This study evaluates overall survival (OS) between liver transplantation (LT) and liver resection (LR), while assessing the effect of margin status, in children with hepatocellular carcinoma (HCC). METHODS: The National Cancer Database was queried (2004-2015) for children (<18 years) with non-metastatic HCC undergoing surgery. RESULTS: One hundred six children with HCC treated surgically (LT 34, LR 72) were identified. For T1 stage, no difference in OS was observed for LT vs. margin-negative liver resection [LR(-)] (log-rank, p = 0.47). For T2/T3/T4 stage, no difference in OS was observed for LT vs. LR(-) (log-rank, p = 0.08); both subgroups exhibited superior OS vs. margin-positive liver resection [LR(+)] (log-rank, LT vs. LR(+): p = 0.001 and LR(-) vs. LR(+): p = 0.04). On multivariable Cox regression: (i) histology (fibrolamellar vs. not) and T stage (T1 vs. T2/T3/T4) were not associated with OS (both p = 0.06), (ii) chemotherapy and size >5 cm were not associated with OS (both p ≥ 0.42), (iii) when compared to LT, both LR(-) (p = 0.03) and LR(+) (p = 0.001) were associated with increased likelihood of mortality. CONCLUSION: Although margin-negative resection may be obtained with LT or LR, early LT consultation is warranted for children at high risk of LR(+) regardless of Milan criteria due to the negative impact of LR(+) on OS. TYPE OF STUDY: Retrospective cohort study. LEVEL OF EVIDENCE: III.

Extracorporeal Membrane Oxygenation in Pediatric Liver Transplantation: A Multicenter Linked Database Analysis and Systematic Review of the Literature.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) can be used to maintain oxygen delivery and provide hemodynamic support in case of circulatory and respiratory failure. Although the role of ECMO has emerged in the setting of adult liver transplantation (LT), data in children are limited. We aimed to describe the characteristics and outcomes of children receiving ECMO support at the time of or following LT. METHODS: All pediatric LT recipients (≤20 y) requiring ECMO support peri-/post-LT were identified from a linked Pediatric Health Information System/Scientific Registry of Transplant Recipients dataset (2002-2018). The Kaplan-Meier method and Cox regression analysis were used to assess post-ECMO survival. A systematic literature review was conducted in accordance with the PRISMA statement. RESULTS: Thirty-four children required ECMO peri-/post-LT. The median time from LT to ECMO was 5 d (interquartile range, 0.0-12.3), and the median ECMO duration was 1 d (interquartile range, 1.0-6.3). Children started on ECMO within 1 d of LT exhibited superior survival compared with those started on ECMO later (P = 0.03). When adjusting for recipient weight, increasing time from LT to ECMO initiation was associated with increased risk of mortality (hazard ratio, 1.03; 95% confidence interval, 1.00-1.06; P = 0.049). Overall, 55.9% (n = 19 of 34) of the patients survived. Twenty-two children receiving ECMO in the peri-/post-LT period were systematically reviewed, and 15 of them survived (68.2%). CONCLUSIONS: With an encouraging >55% patient survival at 6 mo, ECMO should be considered as a viable option in pediatric LT recipients with potentially reversible severe respiratory or cardiovascular failure refractory to conventional treatment.