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The clinical course of COVID-19 in pediatric solid organ transplant recipients remains ambiguous. Though preliminary experiences with adult transplant recipients have been published, literature centered on the pediatric population is limited. We herein report a multi-center, multi-organ cohort analysis of COVID-19-positive transplant recipients ≤ 18 years at time of transplant. Data were collected via institutions' respective electronic medical record systems. Local review boards approved this cross-institutional study. Among 5 transplant centers, 26 patients (62% male) were reviewed with a median age of 8 years. Six were heart recipients, 8 kidney, 10 liver, and 2 lung. Presenting symptoms included cough (n = 12 (46%)), fever (n = 9 (35%)), dry/sore throat (n = 3 (12%)), rhinorrhea (n = 3 (12%)), anosmia (n = 2 (8%)), chest pain (n = 2 (8%)), diarrhea (n = 2 (8%)), dyspnea (n = 1 (4%)), and headache (n = 1 (4%)). Six patients (23%) were asymptomatic. No patient required supplemental oxygen, intubation, or ECMO. Eight patients (31%) were hospitalized at time of diagnosis, 3 of whom were already admitted for unrelated problems. Post-transplant immunosuppression was reduced for only 2 patients (8%). All symptomatic patients recovered within 7 days. Our multi-institutional experience suggests the prognoses of pediatric transplant recipients infected with COVID-19 may mirror those of immunocompetent children, with infrequent hospitalization and minimal treatment, if any, required., (© 2020 Wiley Periodicals LLC.)

Varicella and measles infection represents a significant source of morbidity and mortality for pediatric LT recipients. We evaluated the prevalence and correlates of post-transplant immunity in pediatric LT recipients previously immunized against measles (n = 72) and varicella (n = 67). Sixteen of seventy-two (22%) patients were measles non-immune, and 42/67 (63%) were varicella non-immune after LT. Median time from LT to titers for measles and varicella was 4.0 and 3.3 years, respectively. In the measles cohort, non-immune patients received fewer pretransplant vaccine doses (P = 0.026) and were younger at both time of vaccination (P = 0.006) and LT (P = 0.004) compared with immune patients. Upon multivariable analysis, weight > 10 kg at LT (OR 5.91, 95% CI 1.27-27.41) and technical variant graft (OR 0.07, 95% CI 0.01-0.37) were independently, significantly associated with measles immunity. In the varicella cohort, non-immune patients received fewer pretransplant vaccine doses (P = 0.028), were younger at transplant (P = 0.022), and had less time lapse between their last vaccine and transplant (P = 0.012) compared with immune patients. Upon multivariate analysis, time > 1 year from last vaccine to LT was independently, significantly associated with varicella immunity (OR 3.78, CI 1.30-11.01). This study demonstrates that non-immunity to measles and varicella is a prevalent problem after liver transplantation in children and identifies 3 unique risk factors for non-immunity in this high-risk population., (© 2019 Wiley Periodicals, Inc.)

While much of the discussion regarding expanding the donor pool for pediatric liver transplantation has surrounded the use of technical variant grafts, little attention has been directed toward changes in the deceased donor population. The aim of this study was to investigate trends in the circumstance of the death of deceased donors used for pediatric liver transplantation. All pediatric liver transplant recipients transplanted between 2002 and 2015 were identified in the UNOS database and were categorized based on the donor circumstance of death. There was no significant correlation between year of transplantation and number of pediatric liver transplants performed, pediatric donors, split livers, or living donors. There was a significant downward trend in donors from motor vehicle fatalities and an upward trend in suicide, non-MVA, and death due to natural causes. There was also an upward trend in drowning, one of the most common mechanisms of death among non-MVA in 2015. While the number of donors who died in MVA has fallen, the number of deceased donors who died from suicide, natural causes, and non-MVA, especially drowning, has increased, maintaining the overall number of pediatric deceased donor livers transplanted., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The purpose of this study was to examine the safety, feasibility, acceptability, and preliminary efficacy of a cross-age peer mentoring program created to improve adherence and psychosocial outcomes for pediatric liver transplant recipients. Twenty-two participants were assigned to a "mentor now" or "mentor later" waitlist control group. Tacrolimus SD, a validated measure of adherence, was assessed for six months pre- and post-intervention for both groups. Self-report measures of self-management and HRQOL were completed at recruitment and three months after training. Participant report indicated the acceptability of the intervention. Clinically significant improvement in adherence was detected. No significant changes on the psychosocial outcome measures at follow-up were observed. This study demonstrated that an outpatient-based mentoring program is a safe, feasible, and acceptable option to incorporate within a pediatric liver transplant program with potential for promising application in other transplantation populations as well. These results also suggest that the program may have been associated with meaningful improvement in adherence, although further evaluation is warranted., (© 2013 John Wiley & Sons A/S.)

Studies of DALT in pediatric recipients describe incidence and risk factors, but diagnostic criteria varied. This study reports characteristics and course of pediatric DALT by established diabetes criteria. Retrospective chart review of pediatric LT recipients evaluated for hyperglycemia (1/1/1997-12/30/2009) and matched, non-diabetic controls. DALT: random blood glucose >11.1 mm, ≥ 2 times, with insulin treatment. DALT diagnosed in 8.0% (24/300) included 7/24 (29.2%) with severe hyperglycemia (>27.7 mm), ketoacidosis in 2/24 (8.3%). At diagnosis, age was ≥ 11 yr old in 22/24 (91.7%); body mass was lean (BMIz -0.2 ± 1.5). Mean blood glucose was 24.6 mm with negative diabetes autoantibodies (19/19) and elevated C-peptide (2.3 nm). DALT onset median 5.0 months included 29.1% >12 months. Insulin duration median 4.6 months included 41.7% >6 months. DALT resolved in 83.3% over 4.9 (0.9-9.1) yr. DALT differed from controls by increased preceding rejections, prednisolone dose, tacrolimus level, and triple immunosuppression (all p < 0.01). In conclusion, pediatric DALT occurred in non-obese adolescents with insulin resistance, distinct from diabetes types 1 or 2. DALT was associated with preceding rejection and increased immunosuppression. Blood glucose monitoring, especially during increased immunosuppression following LT, could allow early diagnosis and reduce morbidity., (© 2012 John Wiley & Sons A/S.)

Treatment of primary EV and PTLD in pediatric LT recipients (pLT) involves IS reduction/cessation. Retrospective review of pLT at our institution from 2001-2009 was conducted to characterize risk factors for GR after EV/ PTLD. Of 184 pLT, EV occurred in 61 (33%) at mean 16.5 m (0-82) and PTLD in 18 (9.8%) at mean 17.7 m (3-78) post-LT. Median age at pLT was 11 m (1-245 m) and follow-up six yr. For EV, 86% underwent IS reduction and 51% received antivirals. GR occurred in 12 (27.9%) with EV and 15 (83.3%) after PTLD diagnosis (relative risk of GR for PTLD 2.98). GR treated with methylprednisolone bolus in half and/or oral IS in half. Following GR therapy, four had PTLD relapses, no graft loss and one EV patient required re-transplantation. GR history before EV was a risk factor for GR after EV (p = 0.024). GR at any point after pLT was a risk factor for PTLD (p = 0.001). Children with EV and GR prior to EV should be monitored closely for GR after IS reduction and GR is a significant risk factor for PTLD. Most children with PTLD eventually developed GR., (© 2012 John Wiley & Sons A/S.)

Background: Children have increased prevalence of food allergy (FA) and eosinophilic gastrointestinal disease (EGID) following liver transplantation. The aim of this study was to identify related risk factors., Methods: Chart review of pediatric liver transplant (LT) recipients with de novo FA and/or EGID post-LT and non-allergic controls., Results: We identified 30 (8.5%) children with FA and/or EGID among 352 pediatric LT recipients. Median age at transplant was 0.9 inter-quartile range (IQR 0.6-2.0) years. FA developed at a median 1.0 (IQR 0.5-8.2) yr post-LT and manifested with gastrointestinal symptoms (53%) or urticaria/angioedema (40%). Commonly avoided foods included milk (60%), egg (57%), and peanut (47%). Of the 15 children with FA who underwent endoscopy, 11 had eosinophilic infiltrates in multiple segments of the esophagus alone or in combination with other bowel segments. FA and EGID were linked to transplantation at a younger age (median, 0.9 vs. 5.5 yr), higher frequency of blood eosinophilia, and prior history of rhinitis and atopic dermatitis. Tacrolimus use and tacrolimus serum levels were similar between allergic subjects and controls., Conclusions: Findings suggest that exposure to tacrolimus alone post-LT is insufficient to initiate de novo allergic disease in LT recipients; rather, younger age and underlying predisposition to atopic disease may play larger roles., (© 2012 John Wiley & Sons A/S.)

Introduction: Alagille syndrome (AGS) is an inherited multisystem disorder, and liver transplantation (LT) may be required in pediatric patients with AGS (P-AGS). There are limited data regarding the outcomes of LT in adults with AGS (A-AGS)., Aim: To determine and compare the outcomes of LT in A-AGS vs. P-AGS as well as A-AGS vs. adults with biliary atresia (A-BA)., Methods: Adults (>18 yr), with AGS and BA, and children (≤18 yr), with AGS who underwent isolated first LT between 10/1987 and 5/2008, were identified from the UNOS database., Results: Forty-four of 79,400 adults transplanted for AGS were compared with 407 P-AGS and 56 A-BA, respectively. A-AGS patients had a significantly higher rate of encephalopathy, lower serum albumin, and higher serum creatinine in comparison with P-AGS. One- and five-yr patient and graft survival in A-AGS who underwent LT were not significantly different in comparison with either P-AGS or A-BA (A-AGS patient survival: 95.5%, 90.9%, P-AGS: 88. 7%, 86.2%, A-BA: 89.3%, 87.5%; A-AGS graft survival: 84.1%, 79. 5%, P-AGS: 80.3%, 76%. 1%, A-BA: 82.1%, 78.6%, respectively)., Conclusion: The outcome of first LT in A-AGS is excellent compared with the overall reported adult patient and graft survival. Although A-AGS were sicker than P-AGS at transplant, their outcomes were comparable with that of P-AGS., (© 2011 John Wiley & Sons A/S.)

Pediatric LT recipients are vulnerable to disruptions in their healthcare management and transitioning to self-managed care. This study aimed to examine whether age at transplant and indication for transplant (acute vs. chronic liver disease) influence later self-management skills. Sixty-three LT recipients, aged 14 and older (M = 17.68, s.d. = 3.01), were recruited and asked to complete a healthcare management survey, the Developmentally Based Skills Checklist, adapted for transplant patients, listing 22 behaviors that medically ill adolescents should progressively master. While there were no significant differences between those who received an LT owing to an acute disease vs. those who received an LT owing to a chronic disease, the age at which patients received their transplant did yield significant results, although, overall, these findings were attenuated by current age. However, our findings indicated that males transplanted at a younger age struggled with mastery over their healthcare responsibilities relative to males transplanted later and females in both age groups. There are many possible reasons why the experience of transplant at a younger age could negatively affect or derail healthcare transitions. Future research is necessary to further untangle this relationship; yet, it seems as though longer time living with LT may make transition harder for families., (© 2011 John Wiley & Sons A/S.)

Cytopenias are common among pediatric SOT; however, autoimmune cytopenias are infrequently reported. We report five cases of autoimmune cytopenias in pediatric LT patients: two with isolated IgG-mediated AIHA, two with ITP, and one with Evans syndrome (ITP and AIHA). All patients were maintained on tacrolimus as immunosuppression. Viral illness commonly preceded the autoimmune cytopenias. All patients responded well to medical therapy (steroids, intravenous immunoglobulin, and rituximab) and lowering tacrolimus serum level. Prognosis appears to be worse when more than one cell line (e.g., Evans syndrome) is affected, and/or there is no preceding viral illness. A critical literature review of autoimmune cytopenias in children following SOT is conducted. Autoimmune cytopenias are a rarely reported complication of pediatric SOT, but clinicians taking care of pediatric transplant recipients need to be aware of this complication., (© 2011 John Wiley & Sons A/S.)

PHALT may result from graft dysfunction, portal vein thrombosis, arterio-venous fistulas and can lead to GIB, commonly from bleeding esophageal varices. We present three children with GIB requiring multiple blood transfusions that were diagnosed with RY Loop bleeding. Routine EGD, colonoscopy, and CE failed to reveal the bleeding source. However, enteroscopy revealed large varices at the site of hepaticojejunostomy anastomosis in all. Our experience demonstrates that RY loop varices in children with PHALT are a rare and treatable cause of obscure GI bleeding., (© 2010 John Wiley & Sons A/S.)

Background: Hepatopulmonary syndrome (HPS) is the association of liver disease, hypoxemia, and intrapulmonary vascular dilatations. There are little data on the management of HPS in children other than conventional orthotopic liver transplantation (OLT)., Aims: To describe the patient characteristics, mode of diagnosis, treatment, and outcomes of children with HPS at our center., Methods: Retrospective review of patients diagnosed with HPS between 1997 and 2007 after IRB approval., Results: There were 10 patients, six females; median age at diagnosis of HPS was 12 yr. Six with cirrhosis underwent OLT and had subsequent resolution of HPS and are stable at last follow-up. Of the remaining four, two had cirrhosis. HPS resolved without conventional OLT in the following four patients: hepatitis C after antiviral treatment, biliary atresia with portal hypertension after transjugular intrahepatic portosystemic shunting, Abernethy syndrome after auxiliary partial OLT, and in a child with splenic vein thrombosis after splenectomy., Conclusions: Our series shows resolution of HPS in all patients and 100% survival after conventional OLT. Four children had resolution of HPS after surgical or medical treatments other than conventional OLT. Careful review of clinical status and underlying pathophysiology and anatomy at diagnosis of HPS should inform treatment decisions., (© 2010 John Wiley & Sons A/S.)

Unlabelled: LT is a major medical and surgical challenge in very small patients. Aim of the study is to determine the outcomes after LT in infants ≤ 5 kg at transplant in a large cohort of patients., Methods: Infants ≤ 5 kg who had LT between 10/1987 and 5/2008 were identified from the UNOS database. Risk factors for death and graft loss were analyzed by multivariate logistic regression., Results: Of 11,467 children, 570 (5%) were ≤ 5 kg at LT. Mean age and weight at LT were 0.11 ± 0.48 yr, 4.32 ± 0.74 kg, respectively. One- and five-yr patient and graft survival were 77.7%, 72.2% and 66.1%, 57.6%, respectively. The primary cause of death was infection (25.9%). Recipient age was a predictor of graft loss. Patient and graft survival have improved over time. Life support at transplant was identified as a risk factor for both death and graft loss (p < 0.02, p < 0.01, respectively)., Conclusion: LT recipients ≤5 kg have high mortality and graft loss. Over time, graft survival has improved, although it is still inferior to the overall reported outcomes of pediatric LT. Being on life support at transplant is a significant risk factor for death and graft loss in very small recipients., (© 2011 John Wiley & Sons A/S.)

Patients with hemoglobinopathies may have hepatic involvement, which if severe, can lead to chronic liver disease and a need for liver transplant. Here, we present a case of a 16-yr-old female adolescent who presented to our center with hemoglobin SC disease, obstructive jaundice because of pigmented intrahepatic biliary stones, and progressive liver disease. She underwent a successful liver transplant but a few years later, she developed recurrent cholangitis and graft dysfunction because of recurrent intrahepatic biliary stones. Recurrent formation of intrahepatic stones after liver transplant is a rare and severe complication in patients with hemoglobinopathies. We recommend hypertransfusion therapy and surveillance imaging studies after liver transplant for early detection and prevention of this complication., (© 2011 John Wiley & Sons A/S.)

Patients with HT-1 can develop progressive liver disease and have a high incidence of HCC. LT is indicated in patients with fulminant liver failure, HCC or decompensated chronic liver disease refractory to NTBC. To determine the need for LT and outcomes after LT in children with HT-1. Children with HT-1 who had LT between 10/1987 and 5/2008 were identified from the UNOS database. Of 11,467 children in the UNOS database, 125 (1.1%) required LT secondary to HT-1. Mean age at LT was two and half yr (s.d. ± 3.6 yr). Mean age at LT during the first 10 yr of the study (1.82, s.d. ± 2.86 yr) was significantly lower than in the last decade (3.70, s.d. ± 4.42 yr), p = 0.01. Nearly half of the patients (58, 46.4%) were transplanted between 1988 and 1992. Overall, one- and five-yr patient survival was 90.4% and 90.4%, respectively. LT is a valuable option for children with HT-1 with fulminant liver failure or when medical treatment fails. The rate of LT for children with HT-1 has decreased and age at transplant increased over the last decade most probably reflecting the effect of early diagnosis and treatment with NTBC., (© 2011 John Wiley & Sons A/S.)

A proportion of patients with CF develop cirrhosis and portal hypertension. LT and combined LLT are rarely performed in patients with CF. To determine the outcome of LT and LLT in patients with CF. Patients with CF who had LT or LLT between 10/1987 and 5/2008 were identified from UNOS database. A total of 182 children (<18 yr) and 48 adults underwent isolated LT for CF. Seven more children and eight adults with CF underwent combined LLT. One- and five-yr patient and graft survival were not significantly different in patients who underwent LT in comparison with patients who underwent LLT (patient survival: LT; 83.9%, 75.7%, LLT; 80%, 80%; graft survival: LT; 76.1%, 67.0%, LLT; 80.0%, 80.0%, respectively). The two major causes of death after LT were pulmonary disease (15 patients, 22.7%) and hemorrhage (12 patients, 18.2%). Bilirubin was identified as a risk factor for death, and previous liver transplant and prolonged cold ischemic time were identified as risk factors for graft loss in LT patients. LT is a viable option for children and young adults with CF and end-stage liver disease. Outcome of LLT patients with CF was comparable to the outcome of patients with CF who underwent isolated LT., (© 2011 John Wiley & Sons A/S.)

Unlabelled: Liver transplantation (LT) is lifesaving for patients with Wilson disease (WD) presenting with fulminant hepatic failure (FHF) or chronic liver disease (CLD) unresponsive to treatment., Aim: To determine the outcome of LT in pediatric and adult patients with WD., Methods: United Network for Organ Sharing data on LT from 1987 to 2008 were analyzed. Outcomes were compared for patients requiring LT for FHF and CLD after 2002. Multivariate logistic regression was used to determine risk factors for death and graft loss., Results: Of 90,867 patients transplanted between 1987 and 2008, 170 children and 400 adults had WD. The one- and five-yr patient survival of children was 90.1% and 89% compared to 88.3% and 86% for adults, p = 0.53, 0.34. After 2002, 103 (41 children) were transplanted for FHF and 67 (10 children) for CLD. One- and five-yr patient survival was higher in children transplanted for CLD compared to FHF; 100%, 100% vs. 90%, 87.5% respectively, p = 0.30, 0.32. One- and five-yr patient survival was higher in adults transplanted for CLD compared to FHF; 94.7%, 90.1% vs. 90.3%, 89.7%, respectively, p = 0.36, 0.88. Encephalopathy, partial graft, and ventilator use were risk factors for death by logistic regression., Conclusion: LT is an excellent treatment option for patients with WD. Patients transplanted for CLD had higher patient survival rates than patients with FHF., (© 2010 John Wiley & Sons A/S.)

The purpose of this review is to (i) describe systemic changes made in our clinical practice to facilitate transfer of transplant recipients from the pediatric to the adult service and (ii) provide the rationale for instituting these organizational changes. To determine specific areas patients struggle to master, a survey assessing behaviors indicative of health care management was administered in pediatrics. Based on the results of the survey, all liver transplant recipients who transfer out of pediatrics are given a comprehensive clinical protocol, which includes a transfer checklist containing prerequisite items derived from our prior work. Patients are furthermore invited to enroll in a research study prospectively tracking both medical and psychosocial outcomes at six-month intervals. Data are discussed by the pediatric and adult teams, and additional adjustments to the transfer process are implemented in response. A summary of our clinical interventions and the resources required for implementation are presented. In conclusion, preliminary studies have demonstrated that transplant recipients are vulnerable to disruptions in health care management when they transfer out of pediatrics. This study describes one site's translational efforts to improve the transfer process for both the recipients and the clinicians, thus improving outcomes., (© 2010 John Wiley & Sons A/S.)

Unlabelled: OLT is a life-saving option for ALF., Aim: To evaluate our outcomes in pediatric OLT for ALF., Methods: Retrospective review of our data between 1992 and 2007., Results: Of 142 children with ALF, 126 were listed, of which 40 spontaneously improved, nine died, and 77 underwent OLT (median waiting time four days). Fifty-three children received deceased donor grafts (34 whole and 19 split grafts), and there were 24 living donor grafts. The one- and five-yr patient survival was 87% and 80%, and graft survival 83% and 79%, respectively. Thirteen patients died after OLT, and there were nine retransplants in seven patients. Patient weight, length of stay, creatinine, and infection were significantly associated with death; increased weight and black ethnicity were associated with graft loss on univariate analysis, but not on multivariate analysis. There were no significant differences in patient survival (one and five yr), graft loss, or other complications between the groups., Conclusion: We report the largest single-center study of OLT in pediatric ALF, demonstrating no difference in outcomes between different graft types. Our liberal use of segmental grafts may allow earlier OLT in this high-risk cohort and contribute to our excellent outcomes., (© 2010 John Wiley & Sons A/S.)

Unlabelled: AGS is an inherited disorder involving the liver, heart, eyes, face, and skeleton., Aim: To determine the outcome of LT in children with AGS compared to those with BA., Methods: Children with AGS and BA who had a LT between 10/1987 and 5/2008 were identified from the UNOS database., Results: Of 11 467 children who received a liver transplant, 461 (4.0%) had AGS and 3056 (26.7%) had BA. One- and five-yr patient survival was significantly lower in patients with AGS in comparison with patients with BA (AGS; 82.9%, 78.4%, BA; 89.9%, 84%, respectively). Early death (<30 days from transplant) was significantly higher in AGS than in BA. One- and five-yr graft survival was significantly lower in AGS than in BA (AGS; 74.7%, 61.5%, BA; 81.6%, 70.0%, respectively). Death from graft failure, neurological, and cardiac complications was significantly higher in patients with AGS than in patients with BA. Serum creatinine at transplant, prior LT, and cold ischemic time >12 h were identified as risk factors for death., Conclusion: Children with AGS were older at the time of LT and their one- and five-yr patient and graft survival were significantly lower compared to BA. Risk factors for poor outcome in AGS after LT were identified.

Pediatric PTLD is often associated with primary EBV infection and immunosuppression. The aim was to retrospectively review the spectrum of histologically documented PTLD for two time intervals differentiated by changes in use of molecular EBV monitoring. Eleven of 146 patients (7.5%) in 2001-2005 (Era A) and 10 of 92 (10.9%) in 1993-1997 (Era B) were diagnosed with PTLD. The median age at liver transplantation (0.8 and 0.9 yr, respectively) and the median duration between liver transplant and diagnosis of PTLD (0.6 and 0.7 yr, respectively) were similar in both eras. However, patients in Era A presented with significantly less advanced histological disease compared to patients in Era B (p=0.03). Specifically, nine patients (82%) in Era A had Pl hyperplasia/polymorphic PTLD, whereas in Era B, six had advanced histological disease (five monomorphic and one unclassified). Three transplant recipients in Era B died secondary to PTLD, whereas there were no PTLD-related deaths in Era A (p=0.03). Heightened awareness of risk for PTLD, alterations in baseline immunosuppression regimens, implementation of molecular EBV monitoring, pre-emptive reduction in immunosuppression and improved therapeutic options may have all contributed to a milder PTLD phenotype and improved clinical outcomes., (Copyright (c) 2010 John Wiley & Sons A/S.)

We report a five-yr-old child, presenting three yr after heart transplant with acalculous cholecystitis. Histology revealed EBV negative T-cell PTLD. The disease involved the gallbladder, liver, lungs, and mesenteric lymph nodes. He was treated with chemotherapy, went into remission, but relapsed after 11 months and died.