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SARS-CoV-2 infection during the Omicron period was frequent amongst a cohort of vaccinated pediatric solid organ transplant recipients (pSOTRs) despite robust anti-receptor-binding domain (anti-RBD) antibody response, suggesting poor neutralizing capacity against Omicron subvariants. Breakthrough infections among pSOTRs were overall limited in severity.

Childhood obesity is becoming more prevalent in the United States (US) and worldwide, including among children in need of a liver transplant. Unlike with heart and kidney failure, end-stage liver disease (ESLD) is unique in that no widely available medical technology can re-create the life-sustaining function of a failing liver. Therefore, delaying a life-saving liver transplant for weight loss, for example, is much harder, if not impossible for many pediatric patients, especially those with acute liver failure. For adults in the United States, guidelines consider obesity a contraindication to liver transplant. Although formal guidelines are lacking in children, many pediatric transplant centers also consider obesity a contraindication to a pediatric liver transplant. Variations in practice among pediatric institutions may result in biased and ad hoc decisions that worsen healthcare inequities. In this article, we define and report the prevalence of childhood obesity among children with ESLD, review existing guidelines for liver transplant in adults with obesity, examine pediatric liver transplant outcomes, and discuss the ethical considerations of using obesity as a contraindication to pediatric liver transplant informed by the principles of utility, justice, and respect for persons.

Congenital cytomegalovirus infection is the most common congenital infection. Although most infants with congenital cytomegalovirus infection are asymptomatic at birth, a subset will have readily apparent clinical and/or laboratory manifestations including hepatitis; progression to hepatic failure has not previously been described in term infants who initiated antiviral treatment shortly after birth. We present 2 term infants with congenital cytomegalovirus infection and hepatitis who progressed to hepatic failure despite initial laboratory improvement on therapy.

The SRTR maintains the liver-simulated allocation model (LSAM), a tool for estimating the impact of changes to liver allocation policy. Integral to LSAM is a model that predicts the decision to accept or decline a liver for transplant. LSAM implicitly assumes these decisions are made identically for adult and pediatric liver transplant (LT) candidates, which has not been previously validated. We applied LSAM’s decision-making models to SRTR offer data from 2013 to 2016 to determine its efficacy for adult (≥18) and pediatric (<18) LT candidates, and pediatric subpopulations—teenagers (≥12 to <18), children (≥2 to <12), and infants (<2)—using the area under the receiver operating characteristic (ROC) curve (AUC). For nonstatus 1A candidates, all pediatric subgroups had higher rates of offer acceptance than adults. For non-1A candidates, LSAM’s model performed substantially worse for pediatric candidates than adults (AUC 0.815 vs. 0.922); model performance decreased with age (AUC 0.898, 0.806, 0.783 for teenagers, children, and infants, respectively). For status 1A candidates, LSAM also performed worse for pediatric than adult candidates (AUC 0.711 vs. 0.779), especially for infants (AUC 0.618). To ensure pediatric candidates are not unpredictably or negatively impacted by allocation policy changes, we must explicitly account for pediatric-specific decision making in LSAM.

Learning health systems (LHS) integrate research, improvement, management, and patient care, such that every child receives “the right care at the right time…every time,” that is, evidence-based, personalized medicine. Here, we report our efforts to establish a sustainable, productive, multicenter LHS focused on pediatric liver transplantation. The Starzl Network for Excellence in Pediatric Transplantation (SNEPT) is the first multicenter effort by pediatric liver transplant families and providers to develop shared priorities and a shared agenda for innovation in clinical care. This report outlines SNEPT's structure, accomplishments, and challenges as an LHS. We prioritized 4 initial projects: immunosuppression, perioperative anticoagulation, quality of life, and transition of care. We shared center protocols/management to identify areas of practice variability between centers. We prioritized actionable items that address barriers to providing “the right care at the right time” to every pediatric liver transplant recipient: facilitating transparency of practice variation and the connection of practices to patient outcomes, harnessing existing datasets to reduce the burden of tracking outcomes, incorporating patient-reported outcomes into outcome metrics, and accelerating the implementation of knowledge into clinical practice. This has allowed us to strengthen collaborative relationships, design quality improvement projects, and collect pilot data for each of our priority projects. The field of pediatric liver transplantation can be advanced through application of LHS principles. Going forward, SNEPT will continue to unite patient advocacy, big data, technology, and transplant thought leaders to deliver the best care, while developing new, scalable solutions to pediatric transplantation's most challenging problems.

The current pediatric end‐stage liver disease (PELD) score underestimates pediatric waitlist mortality. Children frequently require PELD exception points to achieve appropriate priority ranking. We developed a new PELD score using serum sodium, creatinine, and updated original PELD components to more accurately rank children and equalize children's mortality risk with the age‐standardized mortality rate of adults. We included children aged younger than 12 years with chronic liver disease, listed for deceased donor livers January 1, 2005‐December 31, 2017. Pediatric candidates (n = 5111) were followed from listing to the earliest of waitlist mortality (death or removal from the list due to being too sick to undergo transplant, n = 339) or 180 days. We incorporated linear splines for the current components of PELD and added sodium and creatinine to the equation. The updated PELD‐Na‐Cr had a cross‐validated AUC ROC of 0.854, vs 0.799 for the original PELD. PELD‐Na‐Cr required 9.44 additional points to equalize children's mortality risk with the age‐standardized mortality rate of adults. PELD‐Na‐Cr better ordered the sickest children and should better prioritize children relative to adults. As a result, PELD‐Na‐Cr could increase pediatric transplant rates and reduce pediatric liver transplant waitlist mortality. PELD‐Na‐Cr updates PELD to better order waitlist mortality risk among children and quantifies the additional points required to equalize the mortality risk of children with that of age‐standardized adults. MacLennan and Orandi's editorial is on page 13.

We report a patient without known preexisting liver disease who presented with hepatopulmonary syndrome (HPS) due to aberrant intrahepatic portal venous development leading to portosystemic shunting. Liver transplantation resulted in resolution of portal hypertension and HPS and sildenafil was safely tolerated in the treatment of persistent fatigue and hypoxemia. Twelve months later, patient has normal allograft function and has returned to normal activity.

Supplemental Digital Content is available in the text.

Split liver transplantation (SLT) is 1 strategy for maximizing the number of deceased donor liver transplants. Recent reports suggest that utilization of SLT in the United States remains low. We examined deceased donor offers that were ultimately split between 2010 and 2014. SLTs were categorized as “primary” and “secondary” transplants. We analyzed allocation patterns and used logistic regression to evaluate factors associated with secondary split discard. Four hundred eighteen livers were split: 54% from adult, 46% from pediatric donors. Of the 227 adult donor livers split, 61% met United Network for Organ Sharing “optimal” split criteria. A total of 770 recipients (418 primary and 352 secondary) were transplanted, indicating 16% discard. Ninety‐two percent of the 418 primary recipients were children, and 47% were accepted on the first offer. Eighty‐seven percent of the 352 secondary recipients were adults, and 7% were accepted on the first offer. Of the 352 pairs, 99% were transplanted in the same region, 36% at the same center. In logistic regression, shorter donor height was associated with secondary discard (odds ratio 0.97 per cm, 95% CI 0.94‐1.00, P= .02). SLT volume by center was not predictive of secondary discard. Current policy proposals that incentivize SLT in the United States could increase the number of transplants to children and adults. In this analysis of deceased donor liver offers in the United States that were ultimately split between 2010‐2014, the authors find that split liver transplants most often benefit a smaller adult (median height of 163cm) and a child, only 61% of adult deceased donor livers split met “optimal” split criteria, and shorter donor height was associated with secondary discard.

Vaccine-preventable infections are occurring at epidemic rates both nationally and internationally. At the same time, rates of vaccine hesitancy and refusal are increasing across the country leading to decreased herd immunity. For immunosuppressed transplant recipients, this situation poses great risk. Currently, 1 in 6 pediatric solid organ transplant recipients is hospitalized with a vaccine-preventable infection in the first 5 years posttransplant. For many recipients, these infections result in significant morbidity, mortality, and increased hospitalization costs. Surprisingly, despite this risk many transplant recipients are not up-to-date on age appropriate immunizations at the time of transplant and thereafter. As a transplant community, we must prioritize immunizations in both pre and posttransplant care. Research is needed to understand how to monitor immune response to vaccines in immunosuppressed patients and when to optimally immunize patients posttransplant. Finally, recommendations about administration of live vaccines posttransplant may need to be reevaluated in the setting of measles outbreaks and decreased herd immunity.

We aimed to investigate national allocation policies for pediatric liver transplantation (LT). A survey was prepared by the European Society for Paediatric Gastroenterology Hepatology and Nutrition Hepatology Committee in collaboration with the North American Studies of Pediatric Liver Transplantation consortium. The survey was sent to pediatric hepatologists and transplant surgeons worldwide. National data were obtained from centrally based registries. Replies were obtained from 15 countries from 5 of the world continents. Overall donation rate varied between 9 and 35 per million inhabitants. The number of pediatric LTs was 4 to 9 per million inhabitants younger than 18 years for 13 of the 15 respondents. In children younger than 2 years mortality on the waiting list (WL) varied between 0 and 20%. In the same age group, there were large differences in the ratio of living donor LT to deceased donor LT and in the ratio of split liver segments to whole liver. These differences were associated with possible discrepancies in WL mortality. Similarities but also differences between countries were detected. The described data may be of importance when trying to reduce WL mortality in the youngest children.

The aim of the study was to investigate the impact of prioritizing infants, children, adolescents, and the sickest adults (Status 1) for deceased donor livers. We compared outcomes under two “SharePeds” allocation schema, which prioritize children and Status 1 adults for national sharing and enhanced access to pediatric donors or all donors younger than 35 years, to outcomes under the allocation plan approved by the Organ Procurement and Transplant Network in December 2017 (Organ Procurement and Transplantation Network [OPTN] 12-2017). The 2017 Liver Simulated Allocation Model and Scientific Registry of Transplant Recipients data on all US liver transplant candidates and liver offers 7/2013 to 6/2016 were used to predict waitlist deaths, transplants, and post-transplant deaths under the OPTN 12-2017 and SharePeds schema. Prioritizing national sharing of pediatric donor livers with children (SharePeds 1) would decrease waitlist deaths for infants (<2 years, P= 0.0003) and children (2–11 years, P= 0.001), with no significant change for adults (P= 0.13). Prioritizing national sharing of all younger than 35-year-old deceased donor livers with children and Status 1A adults (SharePeds 2) would decrease waitlist deaths for infants, children, and all Status 1A/B patients (P< 0.0001 for each). SharePeds 1 and 2 would increase the number of liver transplants done in infants, children, and adolescents compared to the OPTN-2017 schema (P< 0.00005 for all age groups). Both SharePeds schema would increase the percentage of pediatric livers transplanted into pediatric recipients. Waitlist deaths could be significantly decreased, and liver transplants increased, for children and the sickest adults, by prioritizing children for pediatric livers and with broader national sharing of deceased donor livers.

This study identified increased waitlist and posttransplant mortality in young adults. Explanatory factors are limited and the possibility that unmeasured cofounders explain this effect is not excluded. Supplemental digital content is available in the text.

Children from minoritized/socioeconomically deprived backgrounds suffer disproportionately high rates of uninsurance and graft failure/death after liver transplant. Medicaid expansion was developed to expand access to public insurance. Our objective was to characterize the impact of Medicaid expansion policies on long-term graft/patient survival after pediatric liver transplantation. All pediatric patients (<19 years) who received a liver transplant between January 1, 2005, and December 31, 2020 in the US were identified in the Scientific Registry of Transplant Recipients (N = 8489). Medicaid expansion was modeled as a time-varying exposure based on transplant and expansion dates. We used Cox proportional hazards models to evaluate the impact of Medicaid expansion on a composite outcome of graft failure/death over 10 years. As a sensitivity analysis, we conducted an intention-to-treat analysis from time of waitlisting to death (N = 1 1901). In multivariable analysis, Medicaid expansion was associated with a 30% decreased hazard of graft failure/death (hazard ratio, 0.70; 95% confidence interval, 0.62, 0.79; P< .001) after adjusting for Black race, public insurance, neighborhood deprivation, and living in a primary care shortage area. In intention-to-treat analyses, Medicaid expansion was associated with a 72% decreased hazard of patient death (hazard ratio, 0.28; 95% confidence interval, 0.23-0.35; P< .001). Policies that enable broader health insurance access may help improve outcomes and reduce disparities for children undergoing liver transplantation.

Supplemental digital content is available in the text.

Chronic infection with hepatitis B affects nearly 350 million individuals worldwide and is the leading cause of hepatocellular carcinoma and liver cirrhosis. Universal infant immunization has decreased rates of HBV infection, although transmission continues to occur via vertical (mother-to-child) and horizontal (sexual, parenteral and household) routes. Treatments are now available for children with chronic HBV infection, but appropriate selection of those most likely to respond to treatment is important. Interferon α and lamivudine are currently approved in the US for the treatment of children older than 2 years of age who have chronic HBV infection. Hepatitis C infection affects almost 170 million individuals worldwide. Of individuals exposed to HCV, 60–80% develop chronic hepatitis, and 10–15% of those chronically infected develop cirrhosis within several decades. No vaccine exists for HCV; therefore, prevention of parenteral transmission is important. A high index of suspicion is essential for the diagnosis of HCV infection given its silent clinical presentation. Appropriate evaluation of infected individuals is warranted when considering their suitability for therapy. Interferon α and ribavirin, used in combination, are currently approved in the US for the treatment of children older than 3 years of age with chronic HCV infection.

Mutational analysis of 30 recurrent known mutations detects only about 58% of Hispanic cystic fibrosis (CF) chromosomes. The low mutation detection rate has greatly hindered prenatal diagnosis and carrier testing of Hispanic families who have multiple affected children with unidentified cystic fibrosis transmembrane conductance regulator (CFTR) mutations. We recently employed a temporal temperature gradient gel electrophoresis (TTGE) method to effectively scan unknown mutations in the entire CFTR gene. A novel mutation, 2105‐2117 del13insAGAAA was identified in a Hispanic family heterozygous for ΔF508. The discovery of the devastating mutation facilitated the prenatal diagnosis for this family who already had two severely affected children. The fetus was found to be a compound heterozygote of ΔF508/2105‐2117 del13insAGAAA. This case emphasizes the importance of whole gene mutational analysis in patients with a clinical diagnosis of CF, but without the identifiable DNA mutations by routine mutation analysis. Finding of CF mutations in the patient would allow proper genetic counselling and prenatal and carrier detection of at‐risk family members. Copyright © 2000 John Wiley & Sons, Ltd.

Seven patients compound heterozygous for the 3849 + 10kb C → T mutation in the CFTR gene were found among the 152 patients attending the CHLA CF Clinic. The frequency of this mutation accounts for 2.3 and 3.9% of thetotal and Hispanic CF alleles of CHLA patients. These are significantly higher than the 0.6% of the general CF population. The average age of diagnosis of this group of Hispanics is 3.1 years, which is much younger than that reported for CF patients of other ethnicities with the same mutation. Both pancreatic sufficient and pancreatic insufficient patients were observed. It is concluded that the 3849 + 10kb C → T mutation is associated with a variable but potentially mild type of CF.

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