Early Graft Loss With Suspected Seventh-Day Syndrome Following Pediatric Liver Transplantation.

INTRODUCTION: Allograft dysfunction within the first week posttransplant is an uncommon but known complication following liver transplantation. Seventh-Day Syndrome (7DS) is a rare complication of allograft dysfunction following liver transplantation characterized by the rapid clinical deterioration of a formerly well-functioning allograft within the first week posttransplant. The etiology of 7DS is unknown, and treatment options remain limited. While cases of graft survival have been reported, the risk of mortality remains exceedingly high without urgent retransplantation. METHODS: Patient data was retrospectively analyzed and a literature review performed. RESULTS: We present a unique case of split liver transplantation into two pediatric recipients in which one recipient developed rapidly progressive graft failure approximately 1 week postoperatively requiring urgent retransplantation while the other recipient had an unremarkable postoperative course. Upon clinical manifestation of progressive graft failure, the patient was treated with thymoglobulin, rituximab, intravenous immunoglobulin, and plasmapheresis. Despite this, the patient's clinical status continued to decline and she underwent retransplantation 11 days following her initial liver transplant. CONCLUSION: Seventh-Day Syndrome is a rare complication following liver transplantation that is associated with a high risk of morbidity and mortality. Our case adds to the limited literature on 7DS in children and is the first to report a comparative posttransplant clinical course in two recipients who received split grafts from the same donor.

A quality improvement intervention to decrease the decline in renal function in pediatric liver transplant recipients.

BACKGROUND: Chronic kidney disease (CKD) impacts long-term morbidity in pediatric liver transplant (LT) recipients. The prevalence of estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 (eGFR < 90) at our institution was 25% at 1 year post-LT; thus, quality improvement (QI) project was initiated, aiming to decrease the prevalence of eGFR < 90 by at least 20% at 1 year-post LT. METHODS: Children post-LT under 19 years from 2010 to 2018 were included. Three QI interventions were implemented starting 1/2016: documentation of blood pressure percentile (BP%) and eGFR, documentation of a kidney management plan if either was abnormal, and amlodipine initiation prior to hospital discharge after LT. We compared the prevalence of eGFR < 90 at 3, 12, and 24 months after LT in the pre- and post-intervention period. RESULTS: 68 patients in pre- and 42 in post-intervention periods met inclusion criteria. Pre-intervention BP%, eGFR, and kidney management plan were documented at 25%, 10%, and 22%, compared to 71%, 83%, and 71% post-intervention, respectively. 22% of patients were started on amlodipine prior to discharge from LT in the pre- versus 74% in the post-intervention period. Prevalence of eGFR < 90 at 3 m post-LT was 19% in pre- versus 14% in the post-intervention period (p = .31); at 12 months 24% versus 7% (p = .01) and at 24 months 16% versus 6% (p = .13), respectively. Significant non-modifiable risk factors for eGFR < 90 were malignancy (RR = 4.5, p < .0001), metabolic disorder (RR = 2.6, p = .02), and age at transplant (7% increased risk per year of age, p = .007). CONCLUSION: By improving documentation of BP%, eGFR, and kidney management plan, the prevalence of eGFR < 90 was decreased by a relative 74% and 60% at 12 and 24 months post-LT, respectively.

Predictors of survival following liver transplantation for pediatric hepatoblastoma and hepatocellular carcinoma: Experience from the Society of Pediatric Liver Transplantation (SPLIT).

Management of unresectable pediatric hepatoblastoma (HB) and hepatocellular carcinoma (HCC) remains challenging. The Society of Pediatric Liver Transplantation (SPLIT) database was used to study survival predictors in pediatric liver transplantation (LT) for HB and HCC. Event-free survival (EFS), associated risk factors, and postoperative complications were studied in children requiring LT for HB/HCC at 16 SPLIT centers. Three-year EFS was 81% for HB (n = 157) and 62% for HCC (n = 18) transplants. Of HB transplants, 6.9% were PRETEXT II and 15.3% were POST-TEXT I/II. Tumor extent did not impact survival (p = NS). Salvage (n = 13) and primary HB transplants had similar 3-year EFS (62% versus 78%, p = NS). Among HCC transplants, 3-year EFS was poorer in older patients (38% in ≥8-year-olds vs 86% <8-year-olds) and those with larger tumors (48% for those beyond versus 83% within Milan criteria, p = NS). Risk of infection (HR 1.5, 95% CI 1.1-2.2, p = .02) and renal injury (HR 2.4, 95% CI 1.7-3.3, p < .001) were higher in malignant versus nonmalignant LT. Survival is favorable for pediatric HB and HCC LT, including outcomes after salvage transplant. Unexpected numbers of LTs occurred in PRE/POST-TEXT I/II tumors. Judicious patient selection is critical to distinguish tumors that are potentially resectable; simultaneously, we must advocate for patients with unresectable malignancies to receive organs.

Severe Acute Respiratory Syndrome Coronavirus-2 Infection in Children With Liver Transplant and Native Liver Disease: An International Observational Registry Study.

OBJECTIVE: Increased mortality risk because of severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) infection in adults with native liver disease (LD) and liver transplant (LT) is associated with advanced age and comorbid conditions. We aim to report outcomes for children with LD and LT enrolled in the NASPGHAN/SPLIT SARS-CoV2 registry. METHODS: In this multicenter observational cohort study, we collected data from 91 patients <21 years (LD 44, LT 47) with laboratory-confirmed SARS-CoV2 infection between April 21 and September 17, 2020. RESULTS: Patients with LD were more likely to require admission (70% vs 43% LT, P = 0.007) and pediatric intensive care unit (PICU) management (32% vs 4% LT, P = 0.001). Seven LD patients required mechanical ventilation (MV) and 2 patients died; no patients in the LT cohort died or required MV. Four LD patients presented in pediatric acute liver failure (PALF), 2 with concurrent multisystem inflammatory syndrome in children (MIS-C); all recovered without LT. Two LD patients had MIS-C alone and 1 patient died. Bivariable logistic-regression analysis found that patients with nonalcoholic fatty LD (NAFLD) (odds ratio [OR] 5.6, P = 0.02) and LD (OR 6.1, P = 0.01, vs LT) had higher odds of severe disease (PICU, vasopressor support, MV, renal replacement therapy or death). CONCLUSIONS: Although not directly comparable, LT recipients had lower odds of severe SARS-CoV2 infection (vs LD), despite immunosuppression burden. NAFLD patients reported to the registry had higher odds of severe SARS-CoV2 disease. Future controlled studies are needed to evaluate effective treatments and further stratify LD and LT patients with SARS-CoV2 infection.

Progressive multifocal leukoencephalopathy presenting with acute sensorineural hearing loss in an intestinal transplant recipient.

A 20-year-old male presented 3.5 years after intestinal transplantation with rapidly progressive sensorineural hearing loss. Initial brain imaging was consistent with inflammation and/or demyelination. Lumbar puncture was initially non-diagnostic and a broad infectious workup was unrevealing. Three months after presentation, a repeat LP detected JC virus for which tests had not earlier been conducted. He continued to deteriorate despite withdrawal of prior immunosuppression and addition of mirtazapine, maraviroc, and steroids. He died of progressive neurologic decompensation 5 months after his initial presentation. This case highlights progressive multifocal leukoencephalopathy (PML) as a rare complication after solid organ transplantation and acute sensorineural hearing loss as an unusual first presenting symptom of PML. JC virus should be considered in the differential diagnosis of acute sensorineural hearing loss in any immunocompromised patient.

Transient elastography assessment of liver allograft fibrosis in pediatric transplant recipients.

TE measures liver stiffness to assess fibrosis. Its use in post-transplant patients was reported in few small pediatric studies. We evaluated TE ability to predict liver graft fibrosis in a large cohort while comparing it to the performance of APRI and FIB-4. We also investigated the effect of graft type on LSMs. Patients at Boston Children's Hospital who underwent LT and LSM ≤ 1 year from biopsy (2007-2018) were eligible. Ninety-four patients (45%M) aged 1-21 years (89% < 18 years; 13% < 2 years) were eligible. Median time between transplant/biopsy and LSM was 5.1 years and 52 days, respectively. Thirty-nine percent received whole-liver grafts, 54% TV grafts, and 6% as part of MV. At LSM, median ALT was 25 [IQR 16-33] IU/L. Twenty-one percent had METAVIR ≥ F2. LSM was statistically higher among those with significant fibrosis (METAVIR ≥ F2) compared to those with METAVIR F0/F1 (median [IQR] 7.5 [4.6, 13.6] vs 5.1 [4.0, 6.4] kPa, respectively) (P = .005 by Wilcoxon rank-sum test). APRI and FIB-4 distributions were not different across METAVIR stages. The AUROC for LSM was 0.71 (95% CI 0.56-0.85) with an optimal cut-point of 6.5 kPa. Graft type had no influence on the AUROC for LSM. TE is useful for assessing significant graft fibrosis in children and young adult LT recipients and performs better than APRI and FIB-4. TV grafts demonstrate similar correlation with histology as whole-liver grafts.

Society of pediatric liver transplantation: Current registry status 2011-2018.

BACKGROUND: SPLIT was founded in 1995 in order to collect comprehensive prospective data on pediatric liver transplantation, including waiting list data, transplant, and early and late outcomes. Since 2011, data collection of the current registry has been refined to focus on prospective data and outcomes only after transplant to serve as a foundation for the future development of targeted clinical studies. OBJECTIVE: To report the outcomes of the SPLIT registry from 2011 to 2018. METHODS: This is a multicenter, cross-sectional analysis characterizing patients transplanted and enrolled in the SPLIT registry between 2011 and 2018. All patients, <18 years of age, received a first liver-only, a combined liver-kidney, or a combined liver-pancreas transplant during this study period. RESULTS: A total of 1911 recipients from 39 participating centers in North America were registered. Indications included biliary atresia (38.5%), metabolic disease (19.1%), tumors (11.7%), and fulminant liver failure (11.5%). Greater than 50% of recipients were transplanted as either Status 1A/1B or with a MELD/PELD exception score. Incompatible transplants were performed in 4.1%. Kaplan-Meier estimates of 1-year patient and graft survival were 97.3% and 96.6%. First 30 days of surgical complications included reoperation (31.7%), hepatic artery thrombosis (6.3%), and portal vein thrombosis (3.2%). In the first 90 days, biliary tract complications were reported in 13.6%. Acute cellular rejection during first year was 34.7%. At 1 and 2 years of follow-up, 39.2% and 50.6% had normal liver tests on monotherapy (tacrolimus or sirolimus). Further surgical, survival, allograft function, and complications are detailed.

Pediatric post-transplant hepatic kaposi sarcoma due to donor-derived human herpesvirus 8.

In areas of the world where human herpesvirus 8 (HHV-8) is endemic, Kaposi sarcoma (KS) is a common SOT-associated cancer. In the United States, where the virus is not prevalent, PTKS is rare, and there is little literature on pediatric PTKS. We present a North American female who underwent deceased donor, left lateral segment liver transplant for biliary atresia at age 11 months. The donor was a male with no known history of KS, originally from an HHV-8-endemic country. Three months after transplantation, the patient developed liver nodules and portal vein thrombosis. Analysis of needle biopsy established the diagnosis of KS and confirmed that the transformed cells were donor-derived. HHV-8 viremia was detected, and ganciclovir dosing (which had been started prophylactically) was increased. Immunosuppression was changed from tacrolimus to sirolimus. After further disease progression, 8 cycles of paclitaxel were administered. Under this treatment, her nodules regressed, HHV-8 viremia resolved, and she had marked clinic improvement. Notably, the adult recipient of the right liver lobe from the same donor also developed PTKS. This is one of few pediatric PTKS cases described in the literature. It contributes to the mechanistic understanding of PTKS development, illustrating the risk posed by donors from HHV-8-endemic countries, as well as the potential for strong PTKS correlation between multiple recipients of organs from a single shared donor.

Long-term outcomes of liver transplantation for hepatoblastoma: A single-center 14-year experience.

HB is the most common primary liver tumor in children. Complete tumor excision, either by partial resection or by total hepatectomy and liver transplantation, in combination with chemotherapy provides the best chance for cure. We performed a retrospective analysis of patients who underwent liver transplantation for HB and herein present our 14-year single-institution experience. Twenty-five patients underwent liver transplantation for HB at a median age of 26 months (IQR: 15-44). Graft survival was 96%, 87%, and 80% at 1, 3, and 5 years, respectively. There were four patient deaths, three of them due to disease recurrence within the first year post-transplant. Ten-year overall survival was 84%. Three recipients initially presented with pulmonary metastases and underwent resection of metastatic disease, of which two are alive at 3.9 years. Of three patients who underwent salvage transplants, two are alive at 1.5 years after transplant. Non-survivors were associated with lower median alpha fetoprotein value at presentation compared to survivors (21 707 vs 343 214; P = .04). In conclusion, the overall long-term outcome of primary liver transplantation for HB is excellent. Tumor recurrence was the highest contributor to mortality. Even patients with completely treated pulmonary metastases prior to transplant demonstrated a favorable survival.

Bilateral native nephrectomy to reduce oxalate stores in children at the time of combined liver-kidney transplantation for primary hyperoxaluria type 1.

OBJECTIVE: Primary hyperoxaluria type-1 (PH-1) is a rare genetic disorder in which normal hepatic metabolism of glyoxylate is disrupted resulting in diffuse oxalate deposition and end-stage renal disease (ESRD). While most centers agree that combined liver-kidney transplant (CLKT) is the appropriate treatment for PH-1, perioperative strategies for minimizing recurrent oxalate-related injury to the transplanted kidney remain unclear. We present our management of children with PH-1 and ESRD on hemodialysis (HD) who underwent CLKT at our institution from 2005 to 2015. METHODS: On chart review, three patients (2 girls, 1 boy) met study criteria. Two patients received deceased-donor split-liver grafts, while one patient received a whole liver graft. All patients underwent bilateral native nephrectomy at transplant to minimize the total body oxalate load. Median preoperative serum oxalate was 72 µmol/L (range 17.8-100). All patients received HD postoperatively until predialysis serum oxalate levels fell <20 µmol/L. All patients, at a median of 7.5 years of follow-up (range 6.5-8.9), demonstrated stable liver and kidney function. CONCLUSIONS: While CLKT remains the definitive treatment for PH-1, bilateral native nephrectomy at the time of transplant reduces postoperative oxalate stores and may mitigate damage to the renal allograft.

Hematopoietic stem cell transplantation outcomes for 11 patients with dedicator of cytokinesis 8 deficiency.

BACKGROUND: Dedicator of cytokinesis 8 (DOCK8) deficiency can be cured by allogeneic hematopoietic stem cell transplantation (HSCT). Reports of outcomes are still limited. OBJECTIVE: We sought to analyze the results of HSCT in patients with DOCK8 deficiency and report whether approaches resulting in mixed chimerism result in clinically relevant immune reconstitution. METHODS: We performed a retrospective chart review of 11 patients with DOCK8 deficiency and measured DOCK8 expression and cytokine production. RESULTS: Of 11 patients, 7 received HSCT from related and 4 from unrelated donors; 9 patients received busulfan-based conditioning regimens. Survival was excellent (10 [91%] of 11 patients alive), including a patient who had undergone liver transplantation. Patients showed significant improvements in the frequency and severity of infections. Although eczema resolved in all, food allergies and high IgE levels persisted in some patients. Lymphopenia, eosinophilia, low numbers of naive CD8(+) T cells and switched memory B cells, and TH1/TH2 cytokine imbalance improved in most patients. Although the 8 matched related or unrelated donor recipients had full donor chimerism, all 3 recipients of mismatched unrelated donor HSCT had high levels of donor T-cell chimerism and low B-cell and myeloid cell chimerism (0% to 46%). Almost all switched memory B cells were of donor origin. All patients, including those with mixed chimerism, mounted robust antibody responses to vaccination. CONCLUSION: Allogeneic HSCT ameliorated the infectious and atopic symptoms of patients with DOCK8 deficiency. In patients with mixed chimerism, selective advantage for donor-derived T cells and switched memory B cells promoted restoration of cellular and humoral immunity and protection against opportunistic infection.

Outcomes after discontinuation of routine use of transanastomotic biliary stents in pediatric liver transplantation at a single site.

Routine use of transanastomotic biliary stents (RTBS) for biliary reconstruction in liver transplantation (LT) is controversial, with conflicting outcomes in adult randomized trials. Pediatric literature contains limited data. This study is a retrospective review of 99 patients who underwent first LT (2005-2014). In 2011, RTBS was discontinued at our center. This study describes biliary complications following LT with and without RTBS. 56 (56%) patients had RTBS. Median age at LT was 1.9 yr (IQR 0.7, 8.6); 55% were female. Most common indication for LT was biliary atresia (36%). Most common biliary reconstruction was Roux-en-Y choledochojejunostomy (75% with RTBS, 58% without RTBS, p = 0.09). Biliary complications (strictures, bile leaks, surgical revision) occurred in 23% without significant difference between groups (20% with RTBS, 28% without RTBS, p = 0.33). Patients with RTBS had routine cholangiography via the tube at 6-8 wk; thus, significantly more patients with RTBS had cholangiograms (91% vs. 19%, p < 0.0001). There was no difference in the number of patients who required therapeutic intervention via endoscopic or percutaneous transhepatic cholangiography (11% with RTBS, 19% no RTBS, p = 0.26). Routine use of RTBS for biliary reconstruction in pediatric LT may not be necessary, and possibly associated with need for costlier, invasive imaging without improvement in outcomes.

Treatment and outcomes of immune cytopenias following solid organ transplant in children.

BACKGROUND: Immune cytopenias are a recognized life-threatening complication following pediatric solid organ transplants (SOT), but treatment responses and overall outcome are not well described. The aim of this study was to evaluate the demographic characteristics, response to treatments, and outcomes of a cohort of patients who developed immune cytopenias following SOT. PROCEDURE: In this single center retrospective review, patients with immune cytopenias after SOT were identified by electronic medical record (EMR) search and transplant databases from 1995-2012. RESULTS: Of 764 SOT patients, 19 (2.4%) developed immune cytopenias. Incidence varied widely by transplant type from 1.2% (renal) to 23.5% (multivisceral). Autoimmune hemolytic anemia (AIHA) was the most common immune cytopenia. Overall median time from transplant to immune cytopenia was 8 m and varied by transplant type from 3 m (liver) to 74 m (heart). Standard therapies for immune cytopenias were often used and ineffective. The most effective therapy for the immune cytopenia was changing immunosuppression from tacrolimus to another agent. Three of 19 patients died; none directly attributed to the immune cytopenia. CONCLUSIONS: Immune cytopenias are not rare after SOT, and patients usually do not respond well to traditional first line therapies. Provided that the risk of organ rejection is otherwise manageable, temporary cessation of tacrolimus could be more widely explored in this challenging clinical context. Pediatr Blood Cancer 2015;62:214-218. © 2014 Wiley Periodicals, Inc.

Intravenous N-acetylcysteine in pediatric patients with nonacetaminophen acute liver failure: a placebo-controlled clinical trial.

UNLABELLED: N-acetylcysteine (NAC) was found to improve transplantation-free survival in only those adults with nonacetaminophen (non-APAP) acute liver failure (ALF) and grade 1-2 hepatic encephalopathy (HE). Because non-APAP ALF differs significantly between children and adults, the Pediatric Acute Liver Failure (PALF) Study Group evaluated NAC in non-APAP PALF. Children from birth through age 17 years with non-APAP ALF enrolled in the PALF registry were eligible to enter an adaptively allocated, doubly masked, placebo-controlled trial using a continuous intravenous infusion of NAC (150 mg/kg/day in 5% dextrose in water [D5W]) or placebo (D5W) for up to 7 days. The primary outcome was 1-year survival. Secondary outcomes included liver transplantation-free survival, liver transplantation (LTx), length of intensive care unit (ICU) and hospital stays, organ system failure, and maximum HE score. A total of 184 participants were enrolled in the trial with 92 in each arm. The 1-year survival did not differ significantly (P = 0.19) between the NAC (73%) and placebo (82%) treatment groups. The 1-year LTx-free survival was significantly lower (P = 0.03) in those who received NAC (35%) than those who received placebo (53%), particularly, but not significantly so, among those less than 2 years old with HE grade 0-1 (NAC 25%; placebo 60%; P = 0.0493). There were no significant differences between treatment arms for hospital or ICU length of stay, organ systems failing, or highest recorded grade of HE. CONCLUSION: NAC did not improve 1-year survival in non-APAP PALF. One-year LTx-free survival was significantly lower with NAC, particularly among those <2 years old. These results do not support broad use of NAC in non-APAP PALF and emphasizes the importance of conducting controlled pediatric drug trials, regardless of results in adults.

Clinical and immunophenotype correlating with response to immunotherapy in paediatric patients with primary liver carcinoma. A case series.

BACKGROUND: Paediatric hepatocellular carcinomas (HCC) traditionally arise in the context of a normal structural and functional liver and carry a dismal prognosis. While chemotherapy is the frontline standard, there is emerging interest in the study of immunotherapies for paediatric patients with relapsed/refractory disease. There is limited data to support whether immunotherapies will be of utility in this patient population. METHODS: Six paediatric patients (median age:16 years, range: 12-17 at the time of treatment) with advanced hepatocellular neosplams, either conventional hepatocellular or fibrolamellar carcinoma, were treated with immunotherapy. Patients were consented to institutional genomic profiling and biobanking protocols. Baseline samples and serial tissue samples, when available, were evaluated for somatic mutation rate, actionable gene mutations, and pan-immune bulk RNA expression profiling. Results were correlated with clinical course. FINDINGS: Three patients responded to checkpoint inhibition: one achieved a complete, durable response and the other two, prolonged stable disease. Three additional patients progressed. Diagnostic tissue from the complete responder demonstrated a higher relative mutational burden and robust immune infiltrate. Pre-treatment samples from the three responders demonstrated decreased expression of genes associated with T-cell dysfunction. INTERPRETATION: A subset of patients with primary paediatric hepatocellular tumours will respond to immunotherapy. Immunotherapies are currently under prospective study for relapsed/refractory liver tumours in paediatric patients. Results from this report support the prospective collection of serial serum and tissue samples which may further identify genomic and immunophenotypic patterns predictive of response. FUNDING: This work was supported by Philanthropic funds (Pan Mass Challenge, Team Angus and Team Perspective).

Fecal Microbiota Transplant in Pediatric Solid Organ Transplant Recipients.

BACKGROUND: Fecal microbiota transplant (FMT) is an effective treatment for recurrent Clostridioides difficile infection (CDI). Safety concerns around FMT are increased in immunocompromised populations, such as solid organ transplant (SOT) recipients. Outcomes among adult SOT recipients suggest FMT is efficacious and safe; however, pediatric SOT data are lacking. METHODS: We describe the efficacy and safety of FMT among pediatric SOT recipients in a single-center retrospective study from March 2016 to December 2019. Successful FMT was defined as no recurrence of CDI within 2 mo of FMT. We identified 6 SOT recipients ages 4-18 y who received FMT a median of 5.3 y post-SOT. RESULTS: Success after a single FMT was 83.3%. One liver recipient did not achieve cure after 3 FMTs and remains on low-dose vancomycin. One serious adverse event (SAE) occurred; cecal perforation and bacterial peritonitis occurred following colonoscopic FMT coordinated with intestinal biopsy in a kidney transplant recipient. He achieved full recovery and CDI cure. There were no other SAEs. There were no adverse events related to immunosuppression or transplantation status including: bacteremia, cytomegalovirus activation or reactivation, allograft rejection, or allograft loss. CONCLUSIONS: In this limited series, efficacy of FMT in pediatric SOT is comparable to efficacy in the general pediatric recurrent CDI population. There may be an increased risk of procedure-related SAE in SOT patients and larger cohort studies are needed.

Safety and Immunogenicity of Live Viral Vaccines in a Multicenter Cohort of Pediatric Transplant Recipients.

Importance: Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions. Objective: To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients. Design, Setting, and Participants: This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody levels at enrollment between January 1, 2002, and February 28, 2023. Eligibility for live vaccine was determined by individual US pediatric solid organ transplant center protocols. Exposures: Exposure was defined as receipt of a posttransplant live vaccine. Transplant recipients received 1 to 3 doses of MMR vaccine and/or 1 to 3 doses of VZV vaccine. Main Outcome and Measure: Safety data were collected following each vaccination, and antibody levels were obtained at 0 to 3 months and 1 year following vaccination. Comparisons were performed using Mann-Whitney U test, and factors associated with development of postvaccination protective antibodies were explored using univariate analysis. Results: The cohort included 281 children (270 [96%] liver, 9 [3%] kidney, 2 [1%] liver-kidney recipients) from 18 centers. The median time from transplant to enrollment was 6.3 years (IQR, 3.4-11.1 years). The median age at first posttransplant vaccine was 8.9 years (IQR, 4.7-13.8 years). A total of 202 of 275 (73%) children were receiving low-level monotherapy immunosuppression at the time of vaccination. The majority of children developed protective antibodies following vaccination (107 of 149 [72%] varicella, 130 of 152 [86%] measles, 100 of 120 [83%] mumps, and 124 of 125 [99%] rubella). One year post vaccination, the majority of children who initially mounted protective antibodies maintained this protection (34 of 44 [77%] varicella, 45 of 49 [92%] measles, 35 of 42 [83%] mumps, 51 of 54 [94%] rubella). Five children developed clinical varicella, all of which resolved within 1 week. There were no cases of measles or rubella and no episodes of graft rejection within 1 month of vaccination. There was no association between antibody response and immunosuppression level at the time of vaccination. Conclusions and Relevance: The findings suggest that live vaccinations may be safe and immunogenic after solid organ transplant in select pediatric recipients and can offer protection against circulating measles, mumps, and varicella.

Health status of patients with Alagille syndrome.

OBJECTIVES: The aim of the study was to assess health-related quality of life (HRQOL) in children with Alagille syndrome (AGS) in comparison with a normative population and other chronic diseases, and also to examine the effect of AGS-specific morbidities on HRQOL. PATIENTS AND METHODS: A cross-sectional study was performed using the Child Health Questionnaire Parent Form 50 (CHQ-PF50) to measure HRQOL in patients with AGS. AGS HRQOL was compared with that of a normative population and those previously studied by the CHQ, including juvenile rheumatoid arthritis, attention-deficit/hyperactivity disorder, and liver transplantation. AGS-specific questions were used in multiple regression analysis to determine correlation of features and symptoms of AGS with HRQOL. RESULTS: Seventy-one patients with AGS, ages 5 to 18 years, were studied. Those families completing surveys demonstrated that children with AGS had significantly lower HRQOL (P < 0.05) compared with the normative sample. In comparison with children with juvenile rheumatoid arthritis, children with AGS had lower psychosocial function scores (P < 0.0005). In comparison with children with attention-deficit/hyperactivity disorder, children with AGS had lower physical function scores (P < 0.0005) but higher psychosocial function scores (P < 0.0005). Children with AGS had lower physical function scores than a liver transplant population (P < 0.05). Regression analysis indicated that cardiac catheterization or surgery, mental health diagnoses, and poor sleep were associated with lower CHQ scores in children with AGS. CONCLUSIONS: In the first descriptive report of HRQOL in a large cohort of patients with AGS, HRQOL was impaired, indicating a significant burden of chronic disease in both physical and psychosocial health. Additional prospective evaluation is needed in multicenter collaboration.

The re-occurrence of cardiomyopathy in propionic acidemia after liver transplantation.

Cardiomyopathy is a frequent complication of propionic acidemia (PA). It is often fatal, and its occurrence is largely independent of classic metabolic treatment modalities. Liver transplantation (LT) is a treatment option for severe PA as the liver plays a vital role in metabolism of the precursors that accumulate in patients with PA. LT in PA is now considered to be a long-lasting and valid treatment to prevent cardiac disease. The subject of this report had severe cardiomyopathy that largely disappeared prior to undergoing a LT. Three years following the transplant, there was recurrence of cardiomyopathy following a surgery that was complicated with a postoperative aspiration pneumonia. On his last hospital admission, he was presented with pulmonary edema and heart failure. He continued with episodes of intractable hypotension, despite maximum inotropic and diuretic support. He died following redirection of care. We conclude that lethal cardiomyopathy may develop several years after successful LT in patients with PA.