BACKGROUND & AIMS: Approximately 10% of children on the liver transplant wait-list in the United States die every year. We examined deceased donor liver offer acceptance patterns and their contribution to pediatric wait-list mortality. METHODS: We performed a retrospective cohort study of children on the US liver transplant wait-list from 2007 through 2014 using national transplant registry databases. We determined the frequency, patterns of acceptance, and donor and recipient characteristics associated with deceased donor liver organ offers for children who died or were delisted compared with those who underwent transplantation. Children who died or were delisted were classified by the number of donor liver offers (0 vs 1 or more), limiting analyses to offers of livers that were ultimately transplanted into pediatric recipients. The primary outcome was death or delisting on the wait-list. RESULTS: Among 3852 pediatric liver transplant candidates, children who died or were delisted received a median 1 pediatric liver offer (inter-quartile range, 0–2) and waited a median 33 days before removal from the wait-list. Of 11,328 donor livers offered to children, 2533 (12%) were transplanted into children; 1179 of these (47%) were immediately accepted and 1354 (53%) were initially refused and eventually accepted for another child. Of 27,831 adults, 1667 (6.0%; median, 55 years) received livers from donors younger than 18 years (median, 15 years), most (97%) allocated locally or regionally. Of children who died or were delisted, 173 (55%) received an offer of 1 or more liver that was subsequently transplanted into another pediatric recipient, and 143 (45%) died or were delisted with no offers. CONCLUSIONS: Among pediatric liver transplant candidates in the US, children who died or were delisted received a median 1 pediatric liver offer and waited a median of 33 days. Of livers transplanted into children, 47% were immediately accepted and 53% were initially refused and eventually accepted for another child. Of children who died or were delisted, 55% received an offer of 1 or more liver that was subsequently transplanted into another pediatric recipient, and 45% died or were delisted with no offers. Pediatric prioritization in the allocation and development of improved risk stratification systems is required to reduce wait-list mortality among children.

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Background & Aims No treatment for nonalcoholic fatty liver disease (NAFLD) has been approved by regulatory agencies. We performed a randomized controlled trial to determine whether 52 weeks of cysteamine bitartrate delayed release (CBDR) reduces the severity of liver disease in children with NAFLD. Methods We performed a double-masked trial of 169 children with NAFLD Activity Scores ≥ 4 at 10 centers. From June 2012 to January 2014, the patients were randomly assigned to receive CBDR or placebo twice daily (300 mg for ≤65 kg, 375 mg for >65–80 kg, 450 mg for >80 kg) for 52 weeks. The primary outcome from the intention to treat analysis was improvement in liver histology over 52 weeks, defined as a decrease in NAFLD Activity Score ≥ 2 points without worsening fibrosis; patients without biopsies from week 52 (17 in the CBDR group and 6 in the placebo group) were considered non-responders. We calculated relative risks (RR) of improvement using stratified Cochran-Mantel-Haenszel analysis. Results There was no significant difference between groups in the primary outcome (28% of children in the CBDR group vs 22% in the placebo group; RR, 1.3; 95% CI, 0.8–2.1; P=.34). However, children receiving CBDR had significant changes in pre-specified secondary outcomes: reduced mean levels of alanine aminotransferase (reduction of 53±88 U/L vs a reduction of 8±77 U/L in the placebo group; P=.02) and aspartate aminotransferase (reduction of 31±52 vs a reduction of 4±36 U/L in the placebo group; P=.008), and a larger proportion had reduced lobular inflammation (in 36% of patients in the CBDR group vs placebo 21% of patients in the placebo group; RR, 1.8; 95% CI, 1.1–2.9; P=.03). In a post-hoc analyses, of children ≤65 kg, those taking CBDR had a 4-fold better chance of histologic improvement (observed in 50% of children in the CBDR group vs 13% in the placebo group; RR, 4.0; 95% CI, 1.3–12.3; P=.005). Conclusions In a randomized trial, we found that 1 year of CBDR did not reduce overall histologic markers of NAFLD compared with placebo in children. Children receiving CBDR did, however, have significant reductions in serum levels of aminotransferase levels and lobular inflammation. ClinicalTrials.gov no: NCT01529268.

Current literature and policy in pediatric liver allocation and organ procurement are reviewed here in narrative fashion, highlighting historical context, ethical framework, technical/procurement considerations, and support for a logical way forward to an equitable pediatric liver allocation system that will improve pediatric wait-list and posttransplant outcomes without adversely affecting adults. Where available, varying examples of successful international pediatric liver allocation and split-liver policy will be compared to current US policy to highlight potential strategies that can be considered globally. Adaptation of longterm immunosuppressive regimens and developments in medical care and surgical techniques have contributed to >90% longterm patient and graft survival for pediatric liver transplant recipients. However, several areas of concern remain including mortality on the waiting list in young candidates and variable wait times. As we strive for better quality of survival, pediatric providers are compelled to recognize that mortality is not the only issue of concern as chronically ill children linger on the waiting list. Longterm morbidity of increased pediatric wait-list times and decreased rates of transplantation may compromise physical, neurological, and social development. Timely transplantation in children will not only reduce mortality but has the potential to improve quality of life and lower societal burden.

Physicians apply for Model for End‐Stage Liver Disease/Pediatric End‐Stage Liver Disease exception points on a case‐by‐case basis to improve an individual patient's chances of receiving a liver transplant. This retrospective cohort study describes trends in the use of exceptions among the pediatric liver waitlist population with chronic liver disease. The cohort (n = 3728) included all children with a diagnosis of chronic liver disease listed in the United Network for Organ Sharing transplant database for first isolated liver transplant between February 27, 2002 and March 31, 2013. Exception score requests were common (34%); 90% of requests were approved. The rate of exception score requests in 2013 was five times that of 2002 (incident rate ratios [IRR] 5.25, 95% confidence interval [CI] 3.19–8.63, p < 0.01). Patients of non‐White race had exception score request rates 13% lower than patients of White race (IRR 0.87, 95% CI 0.77–0.98, p = 0.02). Older patients had lower rates of exception score requests than younger patients (p = 0.03). Request rates varied by region. Time spent at an active exception status nearly tripled the hazard rate for transplantation (hazard ratio = 2.90, 95% CI 2.62–3.21, p < 0.01). There is disparity in use of exceptions by race that is not explained by clinical disease severity, diagnosis, geography or other demographic factors.

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