Pediatric Liver Transplant Candidates Research Articles

Congenital diseases with multi-organ expression as an indication for liver transplantation in children during the first years of life: Integrative approach to improve the outcomes

Pediatric liver transplantation has evolved since the first transplant was performed by Dr. Starzl more than 50 years ago. Innovations in surgical techniques, immunosuppression, and infection control have significantly improved patient outcomes, graft survival, and quality of life. However, further progress depends not only on the discovery of new treatment option but should rely upon the identification of the factors in the perioperative care which contribute to successful outcomes and guide our decision-making process.Indications for pediatric liver transplantation can be divided into three major groups: cholestatic liver conditions, liver based metabolic disorders, and others represented by acute liver failure of different etiologies, tumors, inherited autoimmune diseases, and multiple infectious causes.Many of these conditions manifest themselves with multi organ pathologic expression, requiring earlier interventions to treat acute liver failure or chronic cholestasis leading to failure to thrive. Containment of patient pathology and maintenance of optimal neurologic and extra-hepatic visceral organ function is paramount during the pre - transplant period.Multidisciplinary management of comorbid conditions in complex pediatric liver transplant candidates during the perioperative period with the emphases on optimization and patient selection has never been summarized in the literature. Thant is why this review focuses on a comprehensive, multidisciplinary preoperative evaluation of pediatric patients in whom progressive liver disfunction manifests early in life and eventually requires liver transplantation. We will address multi-organ system involvement, preoperative optimization in anticipation of the complexity of intraoperative care, as well as short- and long-term postoperative management.

Tailoring allocation policies and improving access to paediatric liver transplantation over a 16-year period

Mortality on the paediatric liver transplantation (pLT) waiting list (WL) is still an issue. We analysed the Italian pLT WL to evaluate the intention-to-treat (ITT) success rate and to identify factors influencing success. All children (<18 years) listed for pLT in Italy between 2002-2018 were included (Era 1 [2002-2007]: centre-based allocation; Era 2 [2008-2014]: national allocation; Era 3 [2015-2018]: national allocation+mandatory-split policy). A total of 1,424 patients (median age: 2.0 [IQR 1.0-9.0] years; median weight: 12.0kg [IQR 7-27]) were listed for pLT. Median WL time was 2 days (IQR 1-5) for Status 1 and 44 days (IQR 15-120) for non-Status 1 patients; 1,302 children (91.4%) were transplanted (67.3% with split grafts), while 50 children (3.5%) dropped off the WL (2.5% death, 1.0% clinical deterioration). Predictive factors for receiving LT included Status 1 (hazard ratio [HR] 1.66, p= 0.001), Status 1B (HR 1.96, p= 0.016), Status 2A (HR 2.15, p= 0.024) and each 1-point increase in PELD/MELD score. Children with recipient's weight >25kg, blood group O or awaiting pLT combined with other organs had less chance of being transplanted. ITT patient survival rates were 90.5% at 1 year and 87.5% at 5 years, remaining stable across eras. Risk factors for ITT survival were re-transplantation (HR 5.83, p <0.001), Status 1 (HR 2.28, p= 0.006), Status 1B (HR 2.90, p= 0.014), Status 2A (HR 9.12, p <0.001), recipient weight <6kg (HR 4.53, p <0.001) and low-volume activity (HR 4.38, p= 0.001). In Italy, continuous adaption of paediatric organ allocation policies via the introduction of national allocation, paediatric prioritisation rules and a mandatory-split policy have helped maximise the use of donors for paediatric candidates and to minimise WL mortality without compromising outcomes. Globally, paediatric liver transplant candidates still suffer from high mortality. Over recent decades, the continuous adaption of organ allocation policies in Italy has led to excellent outcomes for children awaiting liver transplantation. The mortality rate of paediatric liver transplant candidates has been minimised to almost zero, mainly using grafts from deceased donors. Paediatric prioritisation rules, national organ exchange organisation and a mandatory-split liver policy have resulted in a unique allocation model for paediatric liver transplant candidates and represent a landmark for the paediatric transplant community.

Center use of technical variant grafts varies widely and impacts pediatric liver transplant waitlist and recipient outcomes in the United States.

To assess the impact of technical variant grafts (TVGs) [including living donor (LD) and deceased donor split/partial grafts] on waitlist (WL) and transplant outcomes for pediatric liver transplant (LT) candidates, we performed a retrospective analysis of Organ Procurement and Transplantation Network (OPTN) data on first-time LT or liver-kidney pediatric candidates listed at centers that performed >10 LTs during the study period, 2004-2020. Center variance was plotted for LT volume, TVG usage, and survival. A composite center metric of TVG usage and WL mortality was developed to demonstrate the existing variation and potential for improvement. Sixty-four centers performed 7842 LTs; 657 children died on the WL. Proportions of WL mortality by center ranged from 0% to 31% and those of TVG usage from 0% to 76%. Higher TVG usage, from deceased donor or LD, independently or in combination, significantly correlated with lower WL mortality. In multivariable analyses, death from listing was significantly lower with increased center TVG usage (HR = 0.611, CI: 0.40-0.92) and LT volume (HR = 0.995, CI: 0.99-1.0). Recipients of LD transplants (HR = 0.637, CI: 0.51-0.79) had significantly increased survival from transplant compared with other graft types, and recipients of deceased donor TVGs (HR = 1.066, CI: 0.93-1.22) had statistically similar outcomes compared with whole graft recipients. Increased TVG utilization may decrease WL mortality in the US. Hence, policy and training to increase TVG usage, availability, and expertise are critical.

Living Donor Liver Transplant Center Volume Influences Waiting List Survival Among Children Listed for Liver Transplantation.

Pediatric living donor liver transplantation (LDLT) remains infrequently performed in the United States and localized to a few centers. This study aimed to compare pediatric waiting list and posttransplant outcomes by LDLT center volume. The Scientific Registry of Transplant Recipients/Organ Procurement and Transplantation Network database was retrospectively reviewed for all pediatric (age <18 y) liver transplant candidates listed between January 1, 2009, and December 31, 2019. The average annual number of LDLT, deceased donor partial liver transplant (DDPLT), and overall (ie, LDLT + DDPLT + whole liver transplants) pediatric liver transplants performed by each transplant center during the study period was calculated. Of 88 transplant centers, only 44 (50%) performed at least 1 pediatric LDLT during the study period. LDLT, DDPLT, and overall transplant center volume were all positively correlated. LDLT center volume was protective against waiting list dropout after adjusting for confounding variables (adjusted hazard ratio, 0.92; 95% confidence interval, 0.86-0.97; P = 0.004), whereas DDPLT and overall center volume were not ( P > 0.05); however, DDPLT center volume was significantly protective against both recipient death and graft loss, whereas overall volume was only protective against graft loss and LDLT volume was not protective for either. High-volume pediatric LDLT center can improve waiting list survival, whereas DDPLT and overall volume are associated with posttransplant survival. Expertise in all types of pediatric liver transplant options is important to optimize outcomes.

Immunogenicity of varicella zoster vaccine in pediatric liver transplantation.

Pediatric liver transplant (LT) candidates often miss complete varicella-zoster virus (VZV) vaccination before LT. We aimed to evaluate the immunogenicity of two doses of VZV vaccines in pediatric LT candidates younger than 2 years and persistence of its immunogenicity after LT. Patients aged 9-24 months were enrolled before LT. The first dose of VZV vaccine was given at 9 months, and the second dose was given at between 1 to 3 months later, and at least 4 weeks before LT. Varicella-zoster IgG (VZG) was used to detect immunoglobulin G antibodies to VZV and was reported as a test value (TV). A test value ≥ 0.9 was considered as seropositive. TV was measured at enrollment, 1 month after the first and the second dose of VZV vaccine, before LT, and 3 and 6 months after LT. Fourteen children were enrolled in this prospective cohort study. The median age at the first and the second dose of VZV vaccine was 11.5 months (IQR 9-12) and 13 months (IQR 12-33), respectively. The seroconversion rate was 66.7% (8/12) and 70% (7/10) after the first and second VZV vaccine doses, respectively. Seven of nine patients who underwent LT had two doses of VZV vaccine. Six patients were seropositive before LT, which persisted at 3 to 6 months after LT. Of two patients who received only one dose, TV was not detected after LT. The two doses of VZV vaccine appeared to be more immunogenic than one dose in pediatric LT candidates aged less than 2 years.

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

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. 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). 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. 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.

Liver simulated allocation model does not effectively predict organ offer decisions for pediatric liver transplant candidates

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.

Under-Vaccination in Pediatric Liver Transplant Candidates with Acute and Chronic Liver Disease-A Retrospective Observational Study of the European Reference Network TransplantChild.

Infection is a serious concern in the short and long term after pediatric liver transplantation. Vaccination represents an easy and cheap opportunity to reduce morbidity and mortality due to vaccine-preventable infection. This retrospective, observational, multi-center study examines the immunization status in pediatric liver transplant candidates at the time of transplantation and compares it to a control group of children with acute liver disease. Findings show only 80% were vaccinated age-appropriately, defined as having received the recommended number of vaccination doses for their age prior to transplantation; for DTP-PV-Hib, less than 75% for Hepatitis B and two-thirds for pneumococcal conjugate vaccine in children with chronic liver disease. Vaccination coverage for live vaccines is better compared to the acute control group with 81% versus 62% for measles, mumps and rubella (p = 0.003) and 65% versus 55% for varicella (p = 0.171). Nevertheless, a country-specific comparison with national reference data suggests a lower vaccination coverage in children with chronic liver disease. Our study reveals an under-vaccination in this high-risk group prior to transplantation and underlines the need to improve vaccination.

Challenging the Traditional Paradigm of Supply and Demand in Pediatric Liver Transplantation Through Nondirected Living Donation: A Case Series.

A gap exists between the demand for pediatric liver transplantation and the supply of appropriate size-matched donors. We describe our center's experience with pediatric liver transplantation using anonymous nondirected living liver donors (ND-LLD). First-time pediatric liver transplant candidates listed at our center between January 2012 and June 2020 were retrospectively reviewed and categorized by donor graft type, and recipients of ND-LLD grafts were described. A total of 13 ND-LLD pediatric liver transplantations were performed, including 8 left lateral segments, 4 left lobes, and 1 right lobe. Of the ND-LLD recipients, 5 had no directed living donor evaluated, whereas the remaining 8 (62%) had all potential directed donors ruled out during the evaluation process. Recipient and graft survival were 100% during a median follow-up time of 445 (range, 70-986) days. Of ND-LLDs, 69% were previous living kidney donors, and 1 ND-LLD went on to donate a kidney after liver donation. Of the ND-LLDs, 46% were approved prior to the recipient being listed. Over time, the proportion of living donor transplants performed, specifically from ND-LLDs, increased, and the number of children on the waiting list decreased. The introduction of ND-LLDs to a pediatric liver transplant program can expand the benefit of living donor liver transplantation to children without a suitable directed living donor while achieving excellent outcomes for both the recipients and donors.

Higher Mortality in Pediatric Liver Transplant Candidates With Sarcopenia.

Little is known about the impact of sarcopenia (reduced muscle mass and function) in pediatric chronic liver disease. We compared psoas muscle surface area (PMSA), measured at the 4th lumbar vertebrae, in children listed for liver transplantation (LT) to that of healthy controls and studied the impact of sarcopenia on transplant-associated outcomes. The effect of PMSA (raw value and z score) on survival was studied using multivariable proportional hazards, whereas the impact of PMSA on other transplant-associated outcomes was assessed by multivariable linear or logistic regression. The correlation of PMSA with anthropometric values and markers of disease severity was studied using Spearman's rank-order correlation. Mean PMSA was significantly lower in LT candidates (n=57, 699.4 ± 591.9 mm2 [mean±SD]) than controls (n=53, 1052.9±960.7 mm2 ; P=0.02). For LT candidates, there was an increased risk of death (either while on the waiting list or following transplantation) with lower PMSA (hazard ratio [HR], 1.6 per 100 mm2 [P=0.03]; 95% confidence interval [CI], 1.1-2.8), amounting to a 4.9 times higher risk of death for every 1 unit decrease in PMSA z score (HR, 4.9 [P=0.05], 95% CI, 1.2-34.5), adjusting for age and sex. PMSA did not correlate with posttransplant length of intubation, hospital length of stay, or perioperative complications. PMSA also did not correlate with calculated (r=0.10, P=0.60) or appealed Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease scores (r=0.10, P=0.69). Pediatric LT candidates have a significant reduction in muscle compared with controls. LT candidates with lower PMSA experience significant increases in mortality. As such, sarcopenia may provide a novel indicator of disease severity in children with chronic liver disease.

Low psoas muscle index as an unfavorable factor in children with end-stage liver disease undergoing liver transplantation.

Sarcopenia is common in cirrhotic adults and associated with waitlist mortality and worse outcome after liver transplantation. Psoas muscle mass has been used to define sarcopenia. Therefore, we aimed to determine the association between psoas muscle mass and waitlist mortality as well as post-transplant outcome in children with end-stage liver disease. Medical records and abdominal imaging of pediatric liver transplant candidates during 2010-2019 were reviewed. A subset of images was measured by two radiologists to determine inter-rater reliability. Psoas muscle surface area was determined at intervertebral lumbar disk 3-4 (L3-4) and 4-5 (L4-5) levels. PMI was calculated by psoas muscle surface area divided by height squared. We included 105 children, most with biliary atresia (84%). Patients with waitlist mortality had lower PMI compared to the ones who survived to transplantation (PMI at L3-4 levels 352.8±162.5 vs. 416.8±136.2mm2 /m2 and at L4-5 levels 497.3±167.8 vs. 571.4±163.4mm2 /m2 , both p=.04), but not in the multivariate analyses. For transplanted patients (n=75), a higher rate of re-operation (39% vs. 15%, p=.03) and longer hospital stay (53 vs. 45days, p=.02) were found in patients with lower PMI. Lower PMI is associated with higher re-operation rate and longer hospital stay following transplantation, but not waitlist mortality. PMI may be taken into consideration with other biomarkers to predict post-transplant complications.

A218 A CASE REPORT OF PSEUDOHYPONATREMIA IN CHOLESTATIC LIVER DISEASE

Abstract Background True hyponatremia in the setting of cholestatic liver disease may signify cirrhosis with fluid overload, and is therefore an ominous sign of deteriorating liver function. In pediatric liver transplant candidates, it is associated with increased waitlist mortality. Pseudohyponatremia however, is a falsely low measurement of plasma sodium when measured by indirect potentiometry. Pseudohyponatremia secondary to hypercholesterolemia is a phenomenon that occurs due to a reduced aqueous fraction of the plasma when levels of cholesterol or triglycerides are greatly elevated. Severe hypercholesterolemia due to Lipoprotein X accumulation may be the cause of pseudohyponatremia in biliary obstruction or cholestasis. Aims To describe a case of pseudohyponatremia secondary to hypercholesterolemia in an infant with Alagille syndrome (ALGS) and cholestatic liver disease. Methods This 7 month-old male with ALGS (confirmed JAGGED1 mutation) and severe cholestasis, failure to thrive, and pruritus, developed new-onset progressive hyponatremia as low as 121 mmol/L at an outside institution. He was therefore transferred to our center for liver transplant assessment due to concerns of progressive liver dysfunction and for management of the hyponatremia. Results Upon admission, the patient was jaundiced but euvolemic, with no evidence of ascites or peripheral edema. Laboratory work drawn at our institution showed conjugated bilirubin of 180 mmol/L, ALT 300 U/L, AST 250 U/L, and GGT 1200 U/L. INR was 1.1 and albumin of 35 g/L. The cholesterol was elevated above 16.8 mmol/L, with high triglycerides 2.68 mmol/L, and the serum appeared visibly lipemic. The sodium level was 138 mmol/L as measured by direct potentiometry due to the visible lipemia. The osmolality of 288 mmol/kg was normal with a normal osmolar gap. Urine osmolality and sodium were also normal. He underwent routine evaluation and was listed for a liver transplant due to the profound cholestasis and growth failure. Conclusions Pseudohyponatremia is an important entity to recognize when caring for patients with cholestatic liver disease and hyponatremia. Both direct potentiometry and indirect potentiometry are currently used for sodium testing in blood in biochemistry laboratories. These measurement techniques show good agreement as long as protein and lipid concentrations in blood are normal, however, hyperlipidemia is a well-recognized cause for error in sodium estimation. It is therefore imperative to evaluate apparent hyponatremia correctly, especially when the patient appears euvolemic clinically and by normal serum osmolality. In this clinical setting, pseudohyponatremia is the likely cause and a workup should be carried out to identify possible underlying etiologies, the most probable being hypercholesterolemia. Failure to recognize this phenomenon may lead to unnecessary and potentially harmful treatments and interventions. Funding Agencies None

Renal Function Parameters and Serum Sodium Enhance Prediction of Wait-List Outcomes in Pediatric Liver Transplantation.

Reliance on exception points to prioritize children for liver transplantation (LT) stems from concerns that the Pediatric End-Stage Liver Disease (PELD) score underestimates mortality. Renal dysfunction and serum sodium disturbances are negative prognosticators in adult LT candidates and various pediatric populations, but are not accounted for in PELD. We retrospectively evaluated the effect of these parameters in predicting 90-day wait-list death/deterioration among pediatric patients (<12 years) listed for isolated LT in the United States between February 2002 and June 2018. Among 4,765 patients, 2,303 (49.3%) were transplanted, and 231 (4.8%) died or deteriorated beyond transplantability within 90 days of listing. Estimated glomerular filtration rate (eGFR) (hazard ratio [HR] 1.09 per 5-unit decrease, 95% confidence interval [CI] 1.06-1.10) and dialysis (HR 7.24, 95% CI 3.57-14.66) were univariate predictors of 90-day death/deterioration (P<0.001). The long-term benefit of LT persisted in patients with renal dysfunction, with LT as a time-dependent covariate conferring a 2.4-fold and 17-fold improvement in late survival among those with mild and moderate-to-severe dysfunction, respectively. Adjusting for PELD, sodium was a significant nonlinear predictor of outcome, with 90-day death/deterioration risk increased at both extremes of sodium (HR 1.20 per 1-unit decrease below 137mmol/L, 95% CI 1.16-1.23; HR per 1-unit increase above 137mmol/L 1.13, 95% CI 1.10-1.17, P<0.001). A multivariable model incorporating PELD, eGFR, dialysis, and sodium demonstrated improved performance and superior calibration in predicting wait-list outcomes relative to the PELD score. Listing eGFR, dialysis, and serum sodium are potent, independent predictors of 90-day death/deterioration in pediatric LT candidates, capturing risk not accounted for by PELD. Incorporation of these variables into organ allocation systems may highlight patient subsets with previously underappreciated risk, augment ability of PELD to prioritize patients for transplantation, and ultimately mitigate reliance on nonstandard exceptions.

Hyponatremia Is Associated With Increased Mortality in Children on the Waiting List for Liver Transplantation.

Background.Our aim was to determine whether hyponatremia is associated with waiting list or posttransplantation mortality in children having liver transplantation (LT).Methods.A retrospective analysis of the united network for organ sharing/organ procurement transplantation network database on pediatric LT performed between 1988 and 2016 was conducted. Hyponatremia was defined as a serum sodium of 130 mEq/L or below. Subjects were divided into 2 age groups: I (0–6 y old) and II (7–18 y old). Patient survival before and after LT, as well as graft survival, were compared in patients with and without hyponatremia. Multivariable Cox proportional hazards models were constructed for perioperative mortality.Results.Data from 6606 children were available for analysis of waiting list mortality, and 4478 for postoperative mortality. The prevalence of hyponatremia at the time of registration was 2.8% and 3.7% at the time of LT. Waiting list mortality in patients with hyponatremia was significantly higher in group I (P < 0.001) but not in group II (P = 0.09). In group I, the relative risk of mortality adjusted to pediatric end-stage liver disease score was significantly associated with hyponatremia (P < 0.001). A sodium level below 130 mEq/L (hazard ration [HR] = 1.7), younger age (group I) (HR = 2.01), and need for dialysis (HR = 2.3) were independent predictors for increased waiting list mortality. There was no difference in overall postoperative patient or graft survival related to hyponatremia.Conclusions.Hyponatremia is associated with increased waiting list mortality for pediatric LT candidates, particularly in younger children. Future studies examining incorporation of age-specific serum sodium levels into organ allocation policies in children seems warranted based on our findings.

Determinants of length of stay after pediatric liver transplantation.

We sought to identify factors that are associated with LOS following pediatric (<18years) liver transplantation in order to provide personalized counseling and discharge planning for recipients and their families. We identified 2726 infants (≤24months) and 3210 children (>24months) who underwent pediatric liver-only transplantation from 2002-2017 using the Scientific Registry of Transplant Recipients. We used multilevel multivariable negative binomial regression to analyze associations between LOS and recipient and donor characteristics and calculated the MLOSR to quantify heterogeneity in LOS across centers. In infants, the median LOS (IQR) was 19 (13-32) days. Hospitalization prior to transplant (ICU ratio:1.46 1.591.70 ; non-ICU ratio:1.08 1.161.23 ), public insurance (ratio:1.03 1.091.15 ), and a segmental graft (ratio:1.08 1.151.22 ) were associated with a longer LOS; thus, we would expect a 1.59-fold longer LOS in an infant admitted to the ICU compared to a non-hospitalized infant with similar characteristics. In children, the median LOS (IQR) was 13 (9-21) days. Hospitalization prior to transplant (ICU ratio:1.49 1.621.77 ; non-ICU ratio:1.34 1.441.56 ), public insurance (ratio:1.02 1.071.13 ), a segmental graft (ratio:1.20 1.271.35 ), a living donor graft (ratio:1.27 1.381.51 ), and obesity (ratio:1.03 1.101.17 ) were associated with a longer LOS. The MLOSR was 1.25 in infants and 1.26 in children, meaning if an infant received a transplant at another center with a longer LOS, we would expect a 1.25-fold difference in LOS driven by center practices alone. While center-level practices account for substantial variation in LOS, consideration of donor and recipient factors can help clinicians provide more personalized counseling for families of pediatric liver transplant candidates.

Oral health-related quality of life among pediatric liver transplant candidates

To assess the impact of oral conditions on the oral health-related quality of life (OHRQoL) of pediatric liver transplant candidates. This cross-sectional study included 60 children aged 13 to 48 months who were liver transplant candidates that attended the AC Camargo Cancer Center, São Paulo, Brazil. On the day of oral examinations, the children's mothers were invited to answer two questionnaires; one related to children's OHRQoL using the B-ECOHIS and another related to socioeconomic/demographic characteristics. Thereafter, a single, adequately trained dentist carried out children's oral examinations for gingival inflammation (Silness-Löe index), dental plaque (Green-Vermillion Simplified index), dental caries (dmft index), developmental defects of enamel (DDE index), tooth discoloration, oral mucosal/lip alterations. The data collected also included socioeconomic/demographic characteristics and liver disease. The adjusted Poisson regression model was used to associate children's socioeconomic/demographic characteristics and clinical conditions to the outcome. The adjusted regression model showed that children with untreated caries lesions (RR = 3.35, p < 0.0001) and tooth discoloration (RR = 1.74, p = 0.04) had poorer total B-ECOHIS scores. Dental discoloration and untreated caries lesions had a negative impact on the OHRQoL in pediatric liver transplant candidates.

Impact of Acuity Circles on Outcomes for Pediatric Liver Transplant Candidates.

In December 2018, United Network for Organ Sharing approved an allocation scheme based on recipients' geographic distance from a deceased donor (acuity circles [ACs]). Previous analyses suggested that ACs would reduce waitlist mortality overall, but their impact on pediatric subgroups was not considered. We applied Scientific Registry of Transplant Recipients data from 2011 to 2016 toward the Liver Simulated Allocation Model to compare outcomes by age and illness severity for the United Network for Organ Sharing-approved AC and the existing donor service area-/region-based allocation schemes. Means from each allocation scheme were compared using matched-pairs t tests. During a 3-year period, AC allocation is projected to decrease waitlist deaths in infants (39 versus 55; P < 0.001), children (32 versus 50; P < 0.001), and teenagers (15 versus 25; P < 0.001). AC allocation would increase the number of transplants in infants (707 versus 560; P < 0.001), children (677 versus 547; P < 0.001), and teenagers (404 versus 248; P < 0.001). AC allocation led to decreased median pediatric end-stage liver disease/model for end-stage liver disease at transplant for infants (29 versus 30; P = 0.01), children (26 versus 29; P < 0.001), and teenagers (26 versus 31; P < 0.001). Additionally, AC allocation would lead to fewer transplants in status 1B in children (97 versus 103; P = 0.006) but not infants or teenagers. With AC allocation, 77% of pediatric donor organs would be allocated to pediatric candidates, compared to only 46% in donor service area-/region-based allocation (P < 0.001). AC allocation will likely address disparities for pediatric liver transplant candidates and recipients by increasing transplants and decreasing waitlist mortality. It is more consistent with federally mandated requirements for organ allocation.

Psychopathology, quality of life, and related factors in pediatric liver transplantation candidates and recipients.

Liver transplantation (LT) has been accepted as a standard treatment of pediatric liver diseases that can progress to end-stage liver disease or lead to acute liver failure. However, there is a lack of studies clarifying quality of life (QoL) and the characteristics and the prevalence of common psychiatric disorders in children before and/or after LT. Thus, this study aimed to investigate QoL and the prevalence of anxiety, depression, and post-traumatic stress disorder (PTSD) in children and adolescents before and after LT and to compare them with healthy controls. The study included 30 children aged 5-18years who were waiting for LT (pTx group) or had undergone LT (Tx group) as the study groups and 20 children for the control group. The PedsQL was used to evaluate QoL, and SCARED, CDI, and the CPTSD-RI were used to evaluate psychopathology. The QoL scores were higher in the control group compared with the study groups in all or most of the dimensions, depending on the reporter. The mean scores of anxiety, depression, and PTSD of the control group were significantly lower than those of the Tx and pTx groups. A significant positive correlation was found between depression, anxiety, and PTSD scores, and a negative correlation was observed between depression, anxiety, and PTSD scores and QoL. Waiting for LT and the transplantation process itself seem to be psychologically traumatic for children. Healthcare providers need to be trained to recognize the symptoms of the main psychiatric disorders.

Impact of the Pediatric End-Stage Liver Disease (PELD) growth failure thresholds on mortality among pediatric liver transplant candidates.

The Pediatric End-Stage Liver Disease (PELD) score is intended to determine priority for children awaiting liver transplantation. This study examines the impact of PELD's incorporation of "growth failure" as a threshold variable, defined as having weight or height <2 standard deviations below the age and gender norm (z-score<2). First, we demonstrate the "growth failure gap" created by PELD's current calculation methods, in which children have z-scores<2 but do not meet PELD's growth failure criteria and thus lose 6-7 PELD points. Second, we utilized United Network for Organ Sharing (UNOS) data to investigate the impact of this "growth failure gap." Among 3291 pediatric liver transplant candidates, 26% met PELD-defined growth failure, and 17% fell in the growth failure gap. Children in the growth failure gap had a higher risk of waitlist mortality than those without growth failure (adjusted subhazard ratio [SHR] 1.78, 95% confidence interval [95% CI] 1.05-3.02, P=.03). They also had a higher risk of posttransplant mortality (adjusted HR 1.55, 95% CI 1.03-2.32, P=.03). For children without PELD exception points (n=1291), waitlist mortality risk nearly tripled for those in the gap (SHR 2.89, 95% CI 1.39-6.01, P=.005). Current methods for determining growth failure in PELD disadvantage candidates arbitrarily and increase their waitlist mortality risk. PELD should be revised to correct this disparity.

Functional status at listing predicts waitlist and posttransplant mortality in pediatric liver transplant candidates.

Functional impairment is associated with mortality in adult liver transplant candidates. This has not been studied in pediatric liver transplant candidates. United Network for Organ Sharing Standard Transplant Analysis and Research files were used to investigate functional status, waitlist mortality, and posttransplant outcomes in children younger than 18 years who were waitlisted in 2006-2016 for primary liver transplant. Functional status was categorized, by using the Lansky Play-Performance Scale (LPPS), as normal/good (80-100), moderately impaired (50-70), or severely impaired (10-40) by center assessment. Among 3250 children not listed as Status 1A, 62% had an LPPS score of 80-100, 25% had a score of 50-70, and 13% had a score of 10-40 at listing. Children with an LPPS score of 10-40 at listing were more likely to die while on the waitlist (standardized hazard ratio 1.85, 95% confidence interval 1.09-3.13, P=.02) in analyses adjusting for being on a ventilator, breathing support, or dialysis and other illness severity measures. For the 2565 children transplanted, an LPPS score of 10-40 at listing drastically increased mortality risk by 1year posttransplant (hazard ratio 5.77, 95% confidence interval 3.05-10.91, P<.0005). LPPS scores of 10-40 and 50-70 both increased the risk of graft loss by 1year. Functional status is an independent predictor of waitlist and posttransplant mortality in pediatric liver transplant candidates. Validated tools for the assessment of functional status in these children would improve our ability to predict mortality risk-and to appropriately prioritize them for transplant.