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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 (

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.

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.

Accurate and reproducible means of measuring the portosystemic gradient are essential for risk stratification and treatment of portal hypertension. To report the reliability of hepatic venous pressure gradients in children with intrahepatic veno-venous collateralization. Between January 2012 and December 2019 (96 months), 39 patients with native livers underwent wedge hepatic venography and hepatic venous pressure gradient measurements at a tertiary pediatric center. All archived images were reviewed for balloon isolation of the hepatic vein and hepatic vein-to-hepatic vein (HV-HV) collaterals. HV-HV collaterals were categorized as present on the basis of non-catheterized segmental venous opacification despite appropriate balloon isolation. Hepatic venous pressure gradient was defined as the difference of wedge and free hepatic venous pressures. Wedge portosystemic gradient was defined as the difference between wedge hepatic venous pressure and right atrial (RA) pressures. For patients subsequently undergoing portal venous catheterization, portosystemic gradient was defined as the difference between main portal vein and RA pressures. Thirteen of 39 (33.3%) patients demonstrated HV-HV collaterals on wedge hepatic venography. The mean hepatic venous pressure gradient was 5.2±3.8 mmHg (range: 0–15 mmHg). The mean hepatic venous pressure gradient was 3.6±2.6 mmHg (range: 0–9 mmHg) in the presence of HV-HV collaterals and 5.9±4.2 mmHg (range: 1–15 mmHg) in the absence of HV-HV collaterals (P=0.043). Twelve (30.8%) patients were found to have varices: 10 gastroesophageal, 1 rectal and 1 stomal. The mean hepatic venous pressure gradient in patients with varices was 5.4±47 mmHg (range: 0–15 mmHg). For patients with varices, mean hepatic venous pressure gradient was 3.0±2.7 mmHg (range: 0–9 mmHg) in the presence of HV-HV collaterals and 10.3±4.1 mmHg (range: 5–15 mmHg) in the absence of HV-HV collaterals (P=0.004). Four (10.3%) patients had extrahepatic portal vein occlusion: 3 with cavernous transformation and 1 with type Ib Abernethy malformation. All patients with extrahepatic portal vein occlusion demonstrated HV-HV collaterals compared with 8 of 35 (22.9%) patients without extrahepatic portal vein occlusion (P=0.002). Four of 39 (10.3%) patients underwent direct portal pressure measurements: 3 via transhepatic and 1 via trans-splenic portal access. All had demonstrated HV-HV collaterals on wedged imaging. One had extrahepatic portal vein occlusion. The mean time between wedge portosystemic gradient and portosystemic gradient measurement was 3.75 days (range: 0–8 days). The mean wedge portosystemic gradient was 4.5±3.1 mmHg (range: 2–9 mmHg) and the mean portosystemic gradient was 14.5±3.7 mmHg (range: 12–20 mmHg) (P=0.006). HV-HV collateralization is frequently observed in children undergoing wedged portal venography and leads to misrepresentative hepatic venous pressure gradients. All patients undergoing hepatic venous pressure gradient measurement should have wedged venography to identify HV-HV collaterals and to qualify measured pressures. Additional techniques to obtain representative pressures in the presence of HV-HV collaterals warrant further investigation.

Introduction To assess the safety, efficacy, and pharmacokinetics of mini-tablet formulations of ombitasvir (OBV), paritaprevir (PTV), ritonavir, and dasabuvir (DSV) with or without ribavirin for 12 weeks in children infected with chronic hepatitis C virus (HCV) genotype (GT) 1. Methods This is an ongoing, open-label, Phase 2/3 study in children 3–11 years old infected with HCV GT1 who were HCV treatment-naïve and non-cirrhotic. Pediatric mini-tablet formulations of OBV, PTV, ritonavir, and DSV plus ribavirin oral solution were administered for 12 weeks based on body weight. Endpoints included SVR12, adverse events (AEs), and pharmacokinetic parameters. Results Overall, 26 children received OBV, PTV, ritonavir, and DSV plus ribavirin; 14 were 3–8 years old and 12 were 9–11 years old; 35% were male; and all had chronic HCV GT1a infection. The SVR12 rate was 96% (25/26; 95% CI 81.1–99.3), with 1 child failing to achieve SVR12 due to non-adherence and treatment discontinuation. Treatment-emergent AEs of Grade ≥ 3 occurred in 3 children; 2 events in 1 child were considered serious; and none were considered treatment-related. No AEs led to discontinuation of study treatment. The most common AEs were headache (27%), fatigue (23%), pyrexia (19%), and vomiting (19%). Pharmacokinetic results showed mini-tablet formulations of OBV, PTV, DSV, and ritonavir drug exposures were comparable to the adult formulation. Conclusion The mini-tablet combination of OBV, PTV, ritonavir, and DSV plus ribavirin to treat HCV GT1a infection for 12 weeks was highly effective and suitable in children 3–11 years of age. Trial Registration ClinicalTrials.gov identifier, NCT02486406. Electronic supplementary material The online version of this article (10.1007/s12325-020-01389-9) contains supplementary material, which is available to authorized users.

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.

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.

While many adult solid organ transplant recipients (SOTRs) have impaired antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, pediatric SOTRs' response has not been assessed.1-2 We report the immunogenicity and safety of BNT162b2 mRNA vaccination in pediatric SOTRs.

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, one in six pediatric solid organ transplant recipients is hospitalized with a vaccine preventable infection in the first five-years post transplant. 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 post transplant care. Research is needed to understand how to monitor immune response to vaccines in immunosuppressed patients and when to optimally immunize patients post transplant. Finally, recommendations about administration of live vaccines post transplant may need to be re-evaluated in the setting of measles outbreaks and decreased herd immunity.

Objectives: We aimed to investigate national allocation policies for pediatric liver transplantation (LT).Method: 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.Results: 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.Conclusions: 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.

BACKGROUND: The number of programs offering a PTH fellowship has grown rapidly over the last 10 years. This study aimed to describe the clinical, didactic, procedural, and research experiences of recent PTH fellowship graduates. In addition, we sought to understand graduates’ post-fellowship professional responsibilities and their perception about the utility of the PTH fellowship. METHODS: An anonymous survey was distributed from February to October 2020 through REDCap to all recent graduates (2015–2019) of an ACGME-approved PTH fellowship program. The survey consisted of 49 questions focused on the PTH fellowship experience. Results were summarized using descriptive statistics. RESULTS: Thirty-eight of 43 graduates (88%) responded to the survey representing 12 PTH fellowship programs. The didactic experience varied; 97% received pathology lectures, 81% radiology lectures, 54% organ allocation lectures, 54% procedural lectures, 57% immunology lectures, and 43% live donation lectures. During the PTH fellowship, the majority of fellows performed >10 liver biopsies (82%) and >5 variceal bandings (58%); however, 63%, 32%, 8%, and 8% never performed paracentesis, variceal sclerotherapy, variceal banding, and liver biopsies, respectively. The majority of fellows (95%) completed a research project during PTH fellowship. Currently, 84% of graduates are employed at a transplant academic institution. All graduates recommended the fellowship. CONCLUSIONS: There is variability in the didactic, clinical, and procedural training among PTH fellowship programs. Although uniformly viewed as a beneficial fellowship year, there is an opportunity to collaborate to create a more standardized training experience.

Objective 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. Methods 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. Results 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. Conclusions 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.

Retrospective studies have demonstrated the efficacy and safety of pediatric and adolescent transjugular intrahepatic portosystemic shunt (TIPS), but long-term outcomes warrant further investigation.To report on the development of hyperplastic hepatic nodular lesion development in children and young adults (21 years) with TIPS patency3 years.Eighteen children and young adults, including 10 (55.6%) females and 8 (44.4%) males, underwent TIPS creation with3 years' patency and follow-up evaluation at a tertiary children's hospital. The mean age at the time of TIPS creation was 12.5±5.1 years (range: 1.5-20.0 years). The mean model for end-stage liver disease (MELD) at the time of TIPS creation was 8.1±1.6 (range: 6-11). Indications for TIPS creation included acute variceal bleeding (8/18, 44.4%), primary (1/18, 5.6%) or secondary (7/18, 38.9%) prevention of varices, portal vein thrombosis (1/18, 5.6%), and splenic sequestration (1/18, 5.6%). Technical successes, intra-procedural parameters, hemodynamic and clinical successes, TIPS patencies, adverse events, imaging evaluations, and follow-ups were recorded.All (100%) TIPS placements were successful; however, a direct intrahepatic portosystemic shunt was created in one (5.6%) patient. Mean reduction of the portosystemic shunt gradient was 9.1±3.3 mmHg (range: 4-16 mmHg). Seventeen (94.4%) patients demonstrated clinical success with resolution of their initial clinical indication for TIPS placement. The 3-year TIPS primary, primary-assisted, and secondary patencies were 83.3% (15/18), 94.4% (17/18), and 100% (18/18), respectively. Two (11.1%) patients developed mild, medically controlled hepatic encephalopathy. One (5.6%) patient developed hepatopulmonary syndrome. Nine (50%) patients developed single or multiple hepatic nodules at a mean imaging surveillance time after TIPS of 4.4±3.0 years (range: 1.5-10.2 years). Six (33.3%) patients developed nodules1 cm with imaging features most consistent with focal nodular hyperplasia or focal nodular hyperplasia-like nodules. The mean follow-up duration was 5.7±2.9 years (range: 3.0-13.1 years).Long-term (3 years) portosystemic shunting via TIPS is associated with the development of hepatic nodular lesions in children. Consequently, children with TIPS may need gray-scale assessment of hepatic parenchyma as part of routine ultrasound exams and extended imaging surveillance until more is understood regarding the natural history of induced nodularity.

BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.

Adult liver transplant programs have heretofore been hesitant to perform liver retransplantation in adult patients who underwent primary liver transplantation as a child (P_A). Areas of concern include: (a) potential disruption in care when transferring from a pediatric to an adult transplant center; (b) generally inferior outcomes of retransplantation; (c) reputation of young adults for non-adherence to post-transplant regimen; and (d) potential higher work effort for equivalent outcomes. To examine these concerns, we reviewed data on all US liver adult retransplants from 10/01/1987 to 9/30/2017. We propensity matched the P_A patients to patients who received both primary and retransplantation as adults (A_A), with ≥550 days between transplants. A mixed Cox proportional hazards model with program size and time period of transplantation as random variables revealed that retransplantation of P_A patients produced no significantly different graft survival or patient survival rates than retransplantation of the matched A_A patients. Therefore, inferior rates of liver retransplantation in these patients and concerns about continuity of care in changing transplant programs are not as believed in the wider liver transplant community. In conclusion, liver transplant centers should be optimistic about retransplanting adults who received their primary transplants as children.

In adults, treatment of hepatitis C virus (HCV) infection with ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) with or without dasabuvir (DSV) and ±ribavirin (RBV) results in high rates of sustained virologic response (SVR). However, these regimens have not been investigated in adolescents. This ongoing, open‐label, phase 2/3 study evaluated the pharmacokinetics, safety, and efficacy of OBV/PTV/r+DSV±RBV treatment for 12 weeks in adolescents infected with HCV genotype (GT) 1 without cirrhosis (part 1) and the safety and efficacy of OBV/PTV/r±DSV±RBV treatment for 12 or 24 weeks in adolescents infected with GT1 or GT4 without cirrhosis or with compensated cirrhosis (parts 1 and 2). Patients were 12‐17 years of age and treatment naive or interferon experienced. Treatment regimens were based on HCV GT and cirrhosis status. Endpoints were SVR at posttreatment week 12 (SVR12), adverse events (AEs), and pharmacokinetic parameters. Thirty‐eight adolescents were enrolled, 66% were female patients, and 76% were White; 42%, 40%, and 18% of patients had HCV GT1a, GT1b, and GT4 infections, respectively. Median age was 15 years (range, 12‐17 years), and 1 patient had cirrhosis. The SVR12 rate was 100% (38/38; 95% confidence interval [CI], 90.8%‐100%). No treatment‐emergent grade 3 or 4 laboratory abnormalities were reported. No serious AEs occurred on treatment, and no AEs led to study drug discontinuation. The most common AEs were headache (21%), fatigue (18%), nasopharyngitis (13%), pruritus (13%), and upper respiratory tract infection (11%). Intensive pharmacokinetic results showed OBV, PTV, DSV, and ritonavir drug exposures were comparable to those seen in adults. Conclusion: Treatment with OBV/PTV/r±DSV±RBV was well tolerated and highly efficacious in adolescents with HCV GT1 or GT4 infection.

Few established criteria exist to prompt angiographic evaluation and intervention for surgically created splenorenal shunts (SRS). Clinical and Doppler ultrasound (DUS) imaging predictors of shunt dysfunction were evaluated in this retrospective study.Consecutive patients undergoing SRS angiography over a 10-year period were retrospectively identified. Preangiography platelet count and DUS measurements of spleen diameter, maximum splenic vein velocity, and maximum shunt velocity were assessed and compared to findings at subsequent catheter angiography.Twenty-six SRS angiograms were performed in 16 patients. Two of the 26 procedures were excluded from analysis due to insufficient baseline preangiography clinical and DUS data. In the remaining 24 cases, significant stenosis/occlusion was confirmed at angiography in 20, whereas wide patency was seen in 4. For the 20 cases of angiographically confirmed significant stenosis/occlusion, when compared to baseline post-SRS creation to immediate preangiography evaluation there was a greater decrease in platelet count (-51.8% vs -19.4%), a greater increase in spleen diameter (+13.4% vs +3.7%), a greater increase in maximum shunt velocity (+74.7% vs +59.7%), and a greater decrease in splenic vein velocity (-25.0% vs -18.5%).Clinical evidence of splenic sequestration and DUS finding of increased maximum shunt velocity correlate with angiographic findings of SRS dysfunction and could be used to help predict the need for shunt intervention.

Malnutrition is a common complication of end-stage liver disease (ESLD) associated with poor liver transplant outcomes. Nasogastric feeds are used for nutritional supplementation, but some patients remain malnourished. Parenteral nutrition (PN) can be effective, but has potential complications. The primary objective was to evaluate the effect of PN on anthropometric measures in children with ESLD awaiting liver transplant. Secondary objectives were evaluation of PN-associated complications, liver function tests, pediatric end-stage liver disease scores, waitlist time, and post-transplant length of stay (total and time in the intensive care unit).A single-center, retrospective chart review analyzing pediatric patients with ESLD receiving PN who were transplanted during a 6-year period. Data were trended and described over time, as were the relationships between anthropometric data and time receiving PN.A total of 44 patients with ESLD were transplanted between January 2010 and December 2015. Eighteen (41%) received PN before transplant; all had biliary atresia with median age at transplant of 10 months (range, 5-18 months). Mid-upper arm circumference and triceps skinfold thickness showed resolution of malnutrition in 7 patients (39%) with normalization of 1 measure in another 4 patients (22%). Of the remaining, 6 had improved z scores and 1 had worsening malnutrition. No deaths occurred in patients receiving PN. Central line infection rates were 3.8/1000 catheter days with 8 total infections in 6 patients over a total of 2117 catheter days.Children with ESLD and malnutrition who have failed enteral feeding may benefit from PN to improve and/or resolve malnutrition before liver transplant.

Objectives To describe the prevalence and long-term outcomes of kidney, liver, and heart transplant for children with an intellectual disability. Study design We performed a retrospective cohort analysis of children receiving a first kidney, liver, or heart-alone transplant in the United Network for Organ Sharing dataset from 2008 to 2017. Recipients with definite intellectual disability were compared with those possible/no intellectual disability. Kaplan-Meier survival estimates were calculated for graft and patient survival. Cox proportional hazard models were used to estimate the association between intellectual disability and graft and patient survival. Results Over the study period, children with definite intellectual disability accounted for 594 of 6747 (9%) first pediatric kidney-alone, 318 of 4566 (7%) first pediatric liver-alone, and 324 of 3722 (9%) first pediatric heart-alone transplant recipients. Intellectual disability was not significantly associated with patient or graft survival among liver and heart transplant recipients. Among kidney transplant recipients, definite intellectual disability was significantly associated with higher graft survival and lower patient survival, but the absolute differences were small. Conclusions Children with intellectual disability account for 7%-9% of pediatric transplant recipients with comparable long-term outcomes to other pediatric recipients. These findings provide important empirical support for policies that include children with intellectual disability as transplant candidates.

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.

We evaluated liver transplantation waitlist and posttransplantation outcomes in those aged 18 to 24 years compared with both younger (0-17 years) and older (25-34 years) registrants and recipients.Using national data from the United Network for Organ Sharing, competing risk, Cox regression and Kaplan-Meier analyses were performed on first-time liver transplant registrants (n = 13 979) and recipients (n = 8718) ages 0 to 34 years between 2002 and 2015.Nonstatus 1A registrants, registrants aged 0 to 17 and 25 to 34 years were less likely to experience dropout from the waiting list compared with those aged 18 to 24 years (adjusted hazard ratio, 0-5 years = 0.36; 6-11 = 0.29; 12-17 = 0.48; 18-24 = 1.00; 25-34 = 0.82). Although there was no difference in risk of graft failure across all age groups, both younger and older age groups had significantly lower risk of posttransplant mortality compared with those aged 18 to 24 years (adjusted hazard ratio, for 0-5 years = 0.53, 6-11 = 0.48, 12-17 = 0.70, 18-24 = 1.00, 25-34 = 0.77). This may be related to lower likelihood of retransplantation after graft failure in those aged 18 to 24 years.This national registry study demonstrates for the first time poorer waitlist and postliver transplant outcomes in young adults ages 18 to 24 years at the time of listing and transplantation compared to older and younger age groups. Given the potential survival benefit in transplanting young adults and the shortage of solid organs for transplant, future studies are critical to identify and target modifiable risk factors to improve waitlist and long-term posttransplant outcomes in 18- to 24-year-old registrants and recipients.

Learning Health Networks (LHN) improve the well-being of populations by aligning clinical care specialists, technology experts, patients and patient advocates, and other thought leaders for continuous improvement and seamless care delivery. A novel LHN focused on pediatric transplantation, the Starzl Network for Excellence in Pediatric Transplantation (SNEPT), convened its inaugural meeting in September 2018. Clinical care team representatives, patients, and patient families/advocates partnered to take part in educational sessions, pain point exercises, and project identification workshops. Participants discussed the global impact of transplant from both a population and individual perspective, identifying challenges and opportunities where the Starzl Network could work to improve outcomes at scale across a variety of transplant-related conditions.

OBJECTIVE 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). METHODS 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. RESULTS Prioritizing national sharing of pediatric donor livers with children (SharePeds 1) would decrease waitlist deaths for infants (

INTRODUCTION Indications for TIPS are well described in adults and involve complications of PHTN. Complications from PHTN are associated with PSG of > 12 mm Hg in adults. It is unclear if these parameters apply to children with PHTN. OBJECTIVE To assess whether adult criteria for TIPS placement can be utilized in children, describe laboratory changes over time, and report outcomes. METHODS We performed a retrospective review of 34 pediatric patients who underwent TIPS, examining indications, radiology, PSG reductions, laboratory changes, and outcomes. RESULTS Most patients had PHTN due to parenchymal liver disease including congenital hepatic fibrosis (n = 5), biliary atresia (n = 5), cystic fibrosis-related liver disease (n = 3) and cavernous transformation of the portal vein (n = 6). Indications for TIPS included variceal bleeding, recurrent ascites, and maintenance of portal vein flow following thrombolysis. Variceal bleeding was observed in six children with PSG

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. Liver Transplantation 23:86-95 2017 AASLD.

Objective We sought to describe the prevalence and outcomes of liver transplantation in children with intellectual disability (ID). We hypothesized that recipients with ID have comparable short-term outcomes compared with those without ID. Methods We performed a retrospective cohort analysis of children receiving a first liver-alone transplant in the United Network for Organ Sharing dataset from 2008 to 2013. Recipients with definite or probable ID were compared to children without ID using χ tests. Kaplan-Meier curves were constructed for patient and graft survival. Cox proportional hazard models were used to estimate the association between ID and graft failure and patient survival. Results During the study period, 254 children with definite (115) or probable (139) ID underwent first liver transplant, accounting for 15% of all first pediatric liver transplants (1721). Recipients with definite ID tended to be male have a metabolic indication for transplant, a lower pediatric end-stage liver disease score at listing than recipients with no ID, and were less likely to receive a living donor transplant. Recipients with ID were more likely to have public insurance and had more treatment-related hospitalizations in the first year than those without ID. Functional status tended to improve in all recipients at follow-up. ID was not significantly associated with patient or graft survival. Conclusions Children with ID form a significant portion of total liver transplant recipients, and their short-term graft and patient survival are comparable with children without ID. Further research is needed to examine long-term outcomes of transplant in this population.

OBJECTIVE: To evaluate risk factors for hepatic artery thrombosis (HAT) and examine the long-term outcomes of graft and patient survival following HAT in pediatric recipients of liver transplantation. STUDY DESIGN: Utilizing multicenter data from the Society of Pediatric Liver Transplantation (SPLIT), Kaplan-Meier and Cox regression analyses were performed on first-time pediatric (aged

Machine learning analyses allow for the consideration of numerous variables in order to accommodate complex relationships that would not otherwise be apparent in traditional statistical methods to better classify patient risk. The Studies of Pediatric Liver Transplantation (SPLIT) registry data was analyzed to determine whether baseline demographic factors and clinical/biochemical factors in the first year post-transplant could predict ideal outcome at 3 years (IO-3) after liver transplantation (LT). Participants who received their first, isolated LT between 2002–2006 and had follow-up data 3 years post-LT were included. IO-3 was defined as alive at 3 years, normal ALT (

Chronic hepatitis C viral infection represents a worldwide viral epidemic. The natural course of hepatitis C virus is less understood in the pediatric population, although fewer children progress to cirrhosis and end-stage liver disease than adults infected. In the last five years, epidemiological and clinical research involving hepatitis C virus-infected children has raised interesting observations regarding the differences in transmission, natural history, and response to treatment in this population.

Children with Alagille syndrome are often considered for liver transplantation, for a number of indications that include refractory pruritus and end-stage liver disease. It is a well-established therapy with reasonable success. The multi-system nature of this condition dictates a considered approach to liver transplant evaluation and management in order to assure a good outcome.

A 14-year-old boy presented with several months of increasing abdominal girth and fatigue. Imaging confirmed massive ascites and hepatic congestion secondary to central hepatic venous obstruction. Several large intrahepatic collateral veins were seen draining via caudate and emissary veins. After an unsuccessful attempt at retrograde recanalization utilizing intravascular ultrasound, the right hepatic vein was recanalized in an antegrade fashion by way of a prominent caudate collateral vein, and subsequently stented. We herein discuss the established treatment options for Budd-Chiari syndrome and describe our experience employing a single-access liver floss technique.

The field of pediatric solid-organ transplantation has significantly evolved since its beginnings in the early 20th century. As advancements have led to the development of innovative surgical techniques and novel medication regimens, transplantation has now become a routine practice leading to an increase in the rates of organ recipients worldwide. The care of pediatric solid-organ transplant recipients differs from adults in several areas not only due to technically challenging surgeries, but mostly due to the complexity of their immunosuppression management. Although there is large variation of pediatric immunosuppression regimens worldwide, the use of calcineurin inhibitors, either tacrolimus or cyclosporine, still forms the backbone of immunosuppression regimens after solid-organ transplantation. Both medications are relatively well tolerated but are known to have long-term side effects, especially nephrotoxicity and neurotoxicity. The goal of care in long-term pediatric survivors of solid-organ transplant now aims to safely minimize exposure to immunosuppression and to achieve long-term graft tolerance.

To assess frailty, a measure of physiologic declines in multiple organ systems, in children with chronic liver disease using a novel pediatric frailty tool.We performed a prospective cross-sectional multicenter study at 17 liver transplantation (LT) centers. 71 children (5-17 years of age), 36 with compensated chronic liver disease (CCLD) and 35 with end-stage liver disease (ESLD) and listed for LT, were assessed for frailty using validated pediatric tools to assess the 5 classic Fried Frailty Criteria-slowness, weakness, exhaustion, diminished physical activity, and shrinkage. Test scores were translated to age- and sex-dependent z scores, generating a maximum frailty score of 10.The median frailty score of the cohort was 4 (IQR 3, 5). Subjects with ESLD had significantly higher frailty scores (median 5; IQR 4, 7) than subjects with CCLD (median 3; IQR 2, 4); (P .0001). Area under the curve receiver operating characteristic for frailty scores to discriminate between ESLD and CCLD was 0.83 (95% CI 0.73, 0.93). Forty-six percent of children with ESLD were frail and there was no correlation between pediatric frailty scores and physician's global assessments (r = -0.24, 95% CI -0.53, 0.10).A novel frailty tool assessed additional dimensions of health, not captured by standard laboratory measures and identified the sickest individuals among a cohort of children with chronic liver disease. This tool may have applicability to other children with chronic disease.

Routine supplementation of iodine in parenteral nutrition (PN) solutions is not current practice in the United States. In this case study, we describe an incidental finding of goiter in a long-term PN-dependent adolescent. With increased iodine screening, we then identified additional patients with undetectable urinary iodine concentrations in our population of children with short bowel receiving long-term PN. We hypothesize that 2 practice changes are possibly reducing iodine provision to long-term PN-dependent patients: transition to alcohol-based skin preparations and lipid minimization.

Iron deficiency is often observed in obese individuals. The iron regulatory hormone hepcidin is regulated by iron and cytokines interleukin (IL) 6 and IL1β. We examine the relationship between obesity, circulating levels of hepcidin, and IL6 and IL1β, and other risk factors in patients with nonalcoholic fatty liver disease (NAFLD) with iron deficiency.We collected data on 675 adult subjects (18 years old) enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Subjects with transferrin saturation20% were categorized as iron deficient, whereas those with transferrin saturation ≥20% were classified as iron normal. We assessed clinical, demographic, anthropometric, laboratory, dietary, and histologic data from patients, and serum levels of hepcidin and cytokines IL6 and IL1β. Univariate and multivariate analysis were used to identify risk factors for iron deficiency.One-third of patients (231 of 675; 34%) were iron deficient. Obesity, diabetes, and metabolic syndrome were more common in subjects with iron deficiency (P.01), compared with those that were iron normal. Serum levels of hepcidin were significantly lower in subjects with iron deficiency (61 ± 45 vs 81 ± 51 ng/mL; P.0001). Iron deficiency was significantly associated with female gender, obesity, increased body mass index and waist circumference, presence of diabetes, lower alcohol consumption, black or American Indian/Alaska Native race (P ≤ .018), and increased levels of IL6 and IL1β (6.6 vs 4.8 for iron normal, P ≤ .0001; and 0.45 vs 0.32 for iron normal, P ≤ .005).Iron deficiency is prevalent in patients with NAFLD and associated with female gender, increased body mass index, and nonwhite race. Serum levels of hepcidin were lower in iron-deficient subjects, reflecting an appropriate physiologic response to decreased circulating levels of iron, rather than a primary cause of iron deficiency in the setting of obesity and NAFLD.

To investigate Doppler US and catheter venogram correlates to improve detection of transplant HVOO and avoid unnecessary invasive imaging procedures.A retrospective review was performed in all pediatric OLT patients undergoing catheter venography of the hepatic veins between 2007 and 2017 at a single large tertiary pediatric liver transplant institution.Forty-four transplant hepatic venograms in 32 OLT patients were included (mean 1.38, range 1-4 venograms per patient). All venograms were preceded by an independent Doppler US examination. Twenty-one (47.7%) venograms were performed for the investigation of suspected HVOO based on Doppler US alone, 19 (43.2%) were performed for TJLB without suspected HVOO, 4 (9.1%) were performed for both. Sixteen (36.3%) instances of50% anastomotic stenosis were identified. Mean peak anastomotic velocities were 208 cm/s and 116 cm/s in the presence and absence of a50% venographic stenosis, respectively (P 0.004). In all cases where there was a monophasic waveform seen on Doppler US, there was a 50% stenosis seen on hepatic vein venogram. In all cases where a triphasic waveform was seen on Doppler US, there was no stenosis seen on hepatic vein venogram.While a Doppler US velocity threshold providing both high sensitivity and specificity has yet to be identified, increasing peak anastomotic velocity and decreasing intrahepatic venous velocity correlate strongly with venographic outflow stenosis. The presence of a triphasic intrahepatic waveform provides good NPV.

Universal immunization against HBV and blood-donor screening for HBV and HCV have greatly decreased the risk of transmission of these viruses; however, a significant number of children still become chronically infected with HBV and HCV. In this Review, the authors consider the epidemiology, transmission, prevention, clinical presentation and natural history, management and screening, and treatment of hepatitis B and C in children. 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.

Ascites is the pathologic accumulation of fluid within the peritoneal cavity. There are many causes of fetal, neonatal and pediatric ascites; however, chronic liver disease and subsequent cirrhosis remain the most common. The medical and surgical management of ascites in children is dependent on targeting the underlying etiology. Broad categories of management strategies include: sodium restriction, diuresis, paracentesis, intravenous albumin, prevention and treatment of infection, surgical and endovascular shunts and liver transplantation. This review updates and expands the discussion of the unique considerations regarding the management of cirrhotic and non-cirrhotic ascites in the pediatric patient.

Background Urea cycle disorders (UCD) are caused by rare inherited defects in the urea cycle enzymes leading to diminished ability to convert ammonia to urea in the liver. The resulting excess of circulating ammonia can lead to central nervous system toxicity and irreversible neurologic damage. Most cases are identified in children. However, UCDs can also be diagnosed in adulthood, and liver transplant is occasionally required. Methods We examined the UNOS database to evaluate outcomes in adult and pediatric patients who underwent liver transplant as treatment for a UCD. We identified 265 pediatric and 13 adult patients who underwent liver transplant for a UCD between 1987 and 2010. Results The majority (68%) of these patients were transplanted before age 5 years. Ornithine transcarbamylase (OTC) deficiency was the most common UCD in both adults and children who underwent transplant. UCD patients who underwent liver transplant were younger, more likely to be male (67%), had lower pediatric end-stage liver disease/model for end-stage liver disease scores, and were more likely to be Caucasian or Asian compared with all other patients transplanted during the same time period. UCD patients did not have an increased utilization of living donor transplantation in this US cohort. Univariate and multivariate risk factor analyses were performed and did not reveal any significant factors that were predictive of post-transplant death or graft loss. Conclusions Excellent outcomes were seen in both children and adults with UCDs who underwent transplant with overall 1-, 5-, and 10-year survivals of 93%, 89%, and 87%, respectively.