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Competing Interests: Dr. Vakili disclosed that he is an advisory board member of Novathena, Inc. and is a co-founder of ZEeST, Inc. Dr. Mullen received funding from Altavant Sciences Pediatric Advisory Board, UptoDate, and Actelion. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Pediatric patients constitute an important group within the general transplant population, given the opportunity to significantly extend their lives with successful transplantation. Children have historically received special consideration under the various abdominal solid organ allocation algorithms, but matching patients with size and weight restrictions with appropriate donors remains an ongoing issue. Here, we describe the historical trends in pediatric organ allocation policies for liver, kidney, intestine, and pancreas transplantation. We also review recent changes to these allocation policies, with particular attention to recent amendments to geographical prioritization, with the dissolution of donor service areas and United Network for Organ Sharing (UNOS) regions and the subsequent creation of acuity circles., (Copyright © 2022. Published by Elsevier Inc.)

TE measures liver stiffness to assess fibrosis. Its use in post-transplant patients was reported in few small pediatric studies. We evaluated TE ability to predict liver graft fibrosis in a large cohort while comparing it to the performance of APRI and FIB-4. We also investigated the effect of graft type on LSMs. Patients at Boston Children's Hospital who underwent LT and LSM ≤ 1 year from biopsy (2007-2018) were eligible. Ninety-four patients (45%M) aged 1-21 years (89% < 18 years; 13% < 2 years) were eligible. Median time between transplant/biopsy and LSM was 5.1 years and 52 days, respectively. Thirty-nine percent received whole-liver grafts, 54% TV grafts, and 6% as part of MV. At LSM, median ALT was 25 [IQR 16-33] IU/L. Twenty-one percent had METAVIR ≥ F2. LSM was statistically higher among those with significant fibrosis (METAVIR ≥ F2) compared to those with METAVIR F0/F1 (median [IQR] 7.5 [4.6, 13.6] vs 5.1 [4.0, 6.4] kPa, respectively) (P = .005 by Wilcoxon rank-sum test). APRI and FIB-4 distributions were not different across METAVIR stages. The AUROC for LSM was 0.71 (95% CI 0.56-0.85) with an optimal cut-point of 6.5 kPa. Graft type had no influence on the AUROC for LSM. TE is useful for assessing significant graft fibrosis in children and young adult LT recipients and performs better than APRI and FIB-4. TV grafts demonstrate similar correlation with histology as whole-liver grafts., (© 2020 Wiley Periodicals LLC.)

Hepatic artery thrombosis (HAT) following pediatric liver transplantation increases morbidity and risk of graft failure. We performed a retrospective chart review of all patients who underwent deceased-donor liver transplantation from August 2002 to July 2016. Multi-organ transplant recipients were excluded. We examined the incidence of HAT at our institution and sought to identify associated donor or recipient risk factors. A total of 127 deceased-donor liver transplant patients with a median age of 1.7 years (IQR 0.67-6.7) were identified. Of those, 14 developed HAT, all weighing under 25 kg. Among 100 patients under 25 kg, whole-liver graft recipients had an odds ratio of 3.98 (95% confidence interval [CI]: 1.03, 15.34; P = .045) for developing HAT compared with split-liver graft recipients. Within the whole-liver recipient group under 25 kg, 11 patients developed HAT with a median donor-to-recipient ratio (DRWR) of 0.9 (IQR: 0.7-1.2) compared with a median DRWR of 1.4 (IQR: 1.1-1.9) for those who did not develop HAT. Multivariate analysis showed DRWR to be an independent risk factor for HAT in patients weighing under 25 kg who received whole organ grafts, with an odds ratio of 3.89 (95% CI: 1.43, 10.54; P = .008) for each 0.5 unit decrease in DRWR. Our results suggest that in recipients under 25 kg 1) split-liver grafts may have a lower rate of HAT and 2) selecting whole organ donors with a higher DRWR may decrease the incidence of HAT., (© 2019 Wiley Periodicals, Inc.)

Objective: Primary hyperoxaluria type-1 (PH-1) is a rare genetic disorder in which normal hepatic metabolism of glyoxylate is disrupted resulting in diffuse oxalate deposition and end-stage renal disease (ESRD). While most centers agree that combined liver-kidney transplant (CLKT) is the appropriate treatment for PH-1, perioperative strategies for minimizing recurrent oxalate-related injury to the transplanted kidney remain unclear. We present our management of children with PH-1 and ESRD on hemodialysis (HD) who underwent CLKT at our institution from 2005 to 2015., Methods: On chart review, three patients (2 girls, 1 boy) met study criteria. Two patients received deceased-donor split-liver grafts, while one patient received a whole liver graft. All patients underwent bilateral native nephrectomy at transplant to minimize the total body oxalate load. Median preoperative serum oxalate was 72 μmol/L (range 17.8-100). All patients received HD postoperatively until predialysis serum oxalate levels fell <20 μmol/L. All patients, at a median of 7.5 years of follow-up (range 6.5-8.9), demonstrated stable liver and kidney function., Conclusions: While CLKT remains the definitive treatment for PH-1, bilateral native nephrectomy at the time of transplant reduces postoperative oxalate stores and may mitigate damage to the renal allograft.

Considerable strides have been made over the last several decades toward improving outcomes in pediatric liver transplantation. Refinements in surgical technique has allowed for the use of living donor and deceased donor split-liver grafts, thus expanding the pool of available organs and reducing waitlist mortality. The use of a multidisciplinary team continues to be paramount in the care of the transplant recipient. With improvements in overall graft and survival, indications for liver transplantation have also broadened. Currently, pediatric transplant patients have a 5-year survival of over 85%. Long-term morbidity is mainly associated with complications from immunosuppression and chronic rejection. Here we review indications for liver transplantation in children, surgical considerations, post-operative complications, and long-term outcomes., (Copyright © 2017. Published by Elsevier Inc.)

Background: Liver transplantation represents a major surgery involving a highly vascular organ. Reports defining the scope of bleeding in pediatric liver transplants are few., Aims: We conducted a retrospective analysis of liver transplants performed at our pediatric tertiary care center to quantify blood loss, blood product utilization, and to determine predictors for massive intraoperative bleeding., Methods: Pediatric patients who underwent isolated liver transplantation at Boston Children's Hospital between 2011 and 2016 were included. The amount of blood product transfused in the perioperative period and the incidence of postoperative complications were reported. Univariable and multivariable logistic regressions were used to determine predictors for massive bleeding, defined as estimated blood loss exceeding one circulating blood volume within 24 hours., Results: Sixty-eight children underwent liver transplantation during the study period and were included in the analysis. Multivariable logistic regression analysis identified the following independent predictors of massive bleeding: preoperative hemoglobin level <8.5 g/dL (OR 11.09, 95% CI 1.87-65.76), INR >1.5 (OR 11.62, 95% CI 2.36-57.26), platelet count <100 10 9 /L (OR 7.92, 95% CI 1.46-43.05), and surgery duration >600 minutes (OR 6.97, 95% CI 0.99-48.92)., Conclusions: Pediatric liver transplantation is associated with substantial blood loss and a significant blood product transfusion burden. A 43% incidence of massive bleeding is reported. Further efforts are needed to improve bleeding management in this high-risk population., (© 2017 John Wiley & Sons Ltd.)

We sought to examine the relationship between liver transplant-related total cost, patient outcome, and hospital resource utilization at freestanding children's hospitals. Using the PHIS database, a retrospective study of 374 patients that underwent liver transplantation at 15 freestanding children's hospitals from July 2010 to December 2012 was performed. One-year graft failure and patient mortality rates from July 2010 to December 2012 for each center were also obtained from the SRTR. There was a 5.1-fold difference in median cost (median $146 444, range $59 487-302 058, P<.001) between all centers. A 2.4-fold difference existed in median LOS (median 15 days, range 9-22 days, P<.001) across centers. Median postoperative ICU stay varied from 0 to 7 days (median 4 days, P<.001). Overall, 30-day readmission rate was 55% (31.3%-100%, P<.001). One-year graft failure varied from 0% to 19.1%, with an overall rate of 5.5% (P=.279). One-year patient mortality for all centers was 2.3% (range 0%-11.1%, P=.016). Higher total cost did not correlate with lower readmission rates, patient mortality, graft failure, or any other variable. These data suggest that identifying practice patterns at low-cost centers and implementing them at higher-cost centers may decrease the cost of pediatric liver transplantation without compromising outcomes., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Routine use of transanastomotic biliary stents (RTBS) for biliary reconstruction in liver transplantation (LT) is controversial, with conflicting outcomes in adult randomized trials. Pediatric literature contains limited data. This study is a retrospective review of 99 patients who underwent first LT (2005-2014). In 2011, RTBS was discontinued at our center. This study describes biliary complications following LT with and without RTBS. 56 (56%) patients had RTBS. Median age at LT was 1.9 yr (IQR 0.7, 8.6); 55% were female. Most common indication for LT was biliary atresia (36%). Most common biliary reconstruction was Roux-en-Y choledochojejunostomy (75% with RTBS, 58% without RTBS, p = 0.09). Biliary complications (strictures, bile leaks, surgical revision) occurred in 23% without significant difference between groups (20% with RTBS, 28% without RTBS, p = 0.33). Patients with RTBS had routine cholangiography via the tube at 6-8 wk; thus, significantly more patients with RTBS had cholangiograms (91% vs. 19%, p < 0.0001). There was no difference in the number of patients who required therapeutic intervention via endoscopic or percutaneous transhepatic cholangiography (11% with RTBS, 19% no RTBS, p = 0.26). Routine use of RTBS for biliary reconstruction in pediatric LT may not be necessary, and possibly associated with need for costlier, invasive imaging without improvement in outcomes., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Liver transplantation (LT) with living-donor (LD-P) and deceased-donor (DD-P) partial grafts for hepatocellular carcinoma (HCC) may be associated with worse outcomes. Using the United Network for Organ Sharing (UNOS), we aimed to: (1) examine the risk of mortality in LT for HCC, (2) to establish if this risk is affected by partial graft use, and (3) to determine if this effect is mitigated by improved tumor-associated risk stratification., Material and Methods: All first-time adult LT recipients were analyzed (3/2002-12/2012), including 2,353 LD-P, 727 DD-P, and 47,833 DD whole (DD-W) grafts. Cox proportional hazards models were used to examine the risk of mortality given HCC. Interaction/subset analyses were used to examine the effect of tumor-risk and graft-type on outcome. Presence of an HCC exception and low alpha-fetoprotein (AFP) level (<66 ng/mL) were considered favorable., Results: Overall, HCC was associated with an increased mortality risk compared to the absence of HCC (HR 1.21 [1.15-1.27]), and the use of partial grafts was noted to further intensify this risk. However, HCC with a favorable risk profile had more comparable outcomes to patients without HCC and this finding was similar across all graft-types (Given LD-P: HR 1.14 [0.76-1.73]; Given DD-P: HR1.05 [0.71-1.56]; Given DD-W: HR1.08 [1.02-1.14]). On subset analysis, all graft types had similar outcomes given either favorable-risk HCC or the absence of HCC., Conclusions: There is no significant difference in outcomes between whole and partial grafts given (1) patients with HCC with a favorable risk-profile or (2) patients without HCC.

The care of pediatric liver transplant recipients has traditionally included postoperative mechanical ventilation. In 2005, we started extubating children undergoing liver transplantation in the operating room according to standard criteria for extubation used for general surgery cases. We reviewed our single-center experience to determine our rates of immediate extubation and practice since that time. The records of 84 children who underwent liver transplantation from 2005 to 2011 were retrospectively reviewed. The immediate extubation rate increased from 33% during 2005-2008 to 67% during 2009-2011. Immediate extubation did not result in an increased reintubation rate in comparison with delayed extubation in the intensive care unit (ICU). Patients undergoing immediate extubation had a trend toward a shorter mean ICU stay as well as a significantly decreased overall hospital length of stay. Our findings suggest that there is a learning curve for instituting immediate extubation in the operating room after liver transplantation and that the majority of pediatric liver recipients can safely undergo immediate extubation., (© 2014 American Association for the Study of Liver Diseases.)

Background: Infants have the highest wait-list mortality of all liver transplantation candidates. Deceased-donor split-liver transplantation, a technique that provides both an adult and pediatric graft, might be the best way to decrease this disproportionate mortality. Yet concern for an increased risk to adult split recipients has discouraged its widespread adoption. We aimed to determine the current risk of graft failure in adult recipients after split-liver transplantation., Study Design: United Network for Organ Sharing data from 62,190 first-time adult recipients of deceased-donor liver transplants (1995-2010) were analyzed (889 split grafts). Bivariate risk factors (p < 0.2) were included in Cox proportional hazards models of the effect of transplant type on graft failure., Results: Split-liver recipients had an overall hazard ratio of graft failure of 1.26 (p < 0.001) compared with whole-liver recipients. The split-liver hazard ratio was 1.45 (p < 0.001) in the pre-Model for End-Stage Liver Disease era (1995-2002) and 1.10 (p = 0.28) in the Model for End-Stage Liver Disease era (2002-2010). Interaction analyses suggested an increased risk of split-graft failure in status 1 recipients and those given an exception for hepatocellular carcinoma. Excluding higher-risk recipients, split and whole grafts had similar outcomes (hazard ratio = 0.94; p = 0.59)., Conclusions: The risk of graft failure is now similar between split and whole-liver recipients in the vast majority of cases, which demonstrates that the expansion of split-liver allocation might be possible without increasing the overall risk of long-term graft failure in adult recipients. Additional prospective analysis should examine if selection bias might account for the possible increase in risk for recipients with hepatocellular carcinoma or designated status 1., (Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Infants have the highest wait-list mortality of all liver transplant candidates. Although previous studies have demonstrated that young children may be at increased risk when they receive partial grafts from adult and adolescent deceased donors (DDs), with few size-matched organs available, these grafts have increasingly been used to expand the pediatric donor pool. We aimed to determine the current adjusted risks of graft failure and mortality in young pediatric recipients of partial DD livers and to determine whether these risks have changed over time. We analyzed 2683 first-time recipients of DD livers alone under the age of 24 months in the United Network for Organ Sharing database (1995-2010), which included 1118 partial DD livers and 1565 whole DD organs. Transplant factors associated with graft loss in bivariate analyses (P < 0.1) were included in multivariate proportional hazards models of graft and patient survival. Interaction analysis was used to examine risks over time (1995-2000, 2001-2005, and 2006-2010). Although there were significant differences in crude graft survival by the graft type in 1995-2000 (P < 0.001), graft survival rates with partial and whole grafts were comparable in 2001-2005 (P = 0.43) and 2006-2010 (P = 0.36). Furthermore, although the adjusted hazards for partial graft failure and mortality were 1.40 [95% confidence interval (CI) = 1.05-1.89] and 1.41 (95% CI = 0.95-2.09), respectively, in 1995-2000, the adjusted risks of graft failure and mortality were comparable for partial and whole organs in 2006-2010 [hazard ratio (HR) for graft failure = 0.81, 95% CI = 0.56-1.18; HR for mortality = 1.02, 95% CI = 0.66-1.71]. In conclusion, partial DD liver transplantation has become less risky over time and now has outcomes comparable to those of whole liver transplantation for infants and young children. This study supports the use of partial DD liver grafts in young children in an attempt to significantly increase the pediatric organ pool., (© 2013 American Association for the Study of Liver Diseases.)

Prematurity and very low birthweight have often been considered relative contraindications to neonatal organ donation. Organ procurement from neonatal donors is further complicated by unclear guidelines regarding neonatal brain death. We report a successful case of multivisceral transplantation using a graft from a 10-day-old, 2.9 kg, neonatal donor born at 36 6/7 wk in a 3.2 kg, three month old with intestinal and liver failure secondary to midgut volvulus. There was immediate liver graft function with correction of recipient coagulopathy, but delayed normalization of laboratory values and delayed return of bowel function. At six-yr post-transplant follow-up, the patient has normal intestine and liver function. Her last histologically confirmed rejection episode was 30 months prior to last follow-up. This case suggests that multivisceral grafts from very young or small neonatal donors may be transplanted successfully in selected cases. We propose a re-examination of the brain death guidelines for premature and young infants to potentially increase the availability of organs for infant recipients., (© 2012 John Wiley & Sons A/S.)

In regions with a limited deceased donor pool, living donor adult liver transplantation (LDALT) has become an important treatment modality for patients with hepatocellular carcinoma (HCC) and cirrhosis. Studies have shown higher recurrence rates of HCC after LDALT in comparison with deceased donor liver transplantation (DDLT). The aim of our study was to examine the outcome results and recurrence rates for patients with HCC who underwent LDALT at our center. During an 8-year period, 139 patients underwent LDALT, of whom 28 (20.1%) had HCC in their explanted livers. The median follow-up was 40.8 months. The mean explant tumor size was 3.3 +/- 1.2, and the mean number of tumors was 1.5 +/- 0.8. Twenty-one patients (75%) had tumors within the Milan criteria, 5 patients had tumors outside the Milan criteria but within the University of California San Francisco (UCSF) criteria, and 2 patients were beyond the UCSF criteria. The overall 1- and 5-year patient and graft survival rates were 96% and 81%, respectively. Survival following LDALT was significantly better than survival following DDLT for HCC during the same time period (P = 0.02). Eight patients (28.6%) developed tumor recurrence. Poor differentiation of tumor cells was the most significant determinant of recurrence. Despite high recurrence rates of HCC following LDALT, overall 5-year survival appears to be excellent.