Immunosuppression after pediatric liver transplant: The parents' perspective.

BACKGROUND: For children with liver transplants (LT), achieving an "ideal outcome" is a balancing act: too little immunosuppression begets graft injury; too much begets systemic complications. We aimed to delineate the parental perspective on this tightrope. METHODS: Parents of children with LT completed an internet-based survey about their child's immunosuppression. RESULTS: Children of respondents (n = 82) were a median 4 years from primary LT (range 0-22); 73% were on immunosuppression monotherapy. Parents' top concerns were related to immunosuppression complications; 46% were more concerned about immunosuppression complications than rejection; only 17% were more concerned about rejection than immunosuppression complications. Among parents of children on immunosuppression monotherapy, 29% still worried more about immunosuppression complications than rejection, 48% expressed equal concern for both. Time since LT (0-4 vs. >4 years) was not associated with concern level for rejection or immunosuppression complications. Caregivers were significantly more certain that their child's immunosuppression regimen was correct to prevent rejection than to mitigate complications (p < .005). CONCLUSION: Caregivers of children with LTs reported higher levels of concern and uncertainty about immunosuppression complications than rejection risk. Understanding parent and patient perspectives on IS, and incorporating them into immunosuppression counseling and decision-making, is critical to achieving truly "ideal" long-term outcomes.

Allocation to pediatric recipients around the world: An IPTA global survey of current pediatric solid organ transplantation deceased donation allocation practices.

BACKGROUND: There has not been a comprehensive global survey of pediatric-deceased donor allocation practices across all organs since the advent of deceased donor transplantation at the end of the 20th century. As an international community that is responsible for transplanting children, we set out to survey the existing landscape of allocation. We aimed to summarize current practices and provide a snapshot overview of deceased donor allocation practices to children across the world. METHODS: The International Registry in Organ Donation and Transplantation (IRODAT, www.irodat.org) was utilized to generate a list of all countries in the world, divided by continent, that performed transplantation. We reviewed the published literature, published allocation policy, individual website references and associated links to publicly available listed allocation policies. Following this, we utilized tools of communication, relationships, and international fellowship to confirm deceased donation pediatric centers and survey pediatric allocation practices for liver, kidney, heart, and lung across the world. We summarize pediatric allocation practices by organ when available using source documents, and personal communication when no source documents were available. RESULTS: The majority of countries had either formal or informal policies directed toward minimizing organ distribution disparity among pediatric patients. CONCLUSION: Children have long-term life to gain from organ donation yet continue to die while awaiting transplantation. We summarize global strategies that have been employed to provide meaningful and sustained benefit to children on the waitlist.

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.

Factors associated with thrombotic and hemorrhagic complications in pediatric liver transplant: A multi-center analysis from the Starzl Network for Excellence in Pediatric Transplantation.

BACKGROUND: Survival after pediatric liver transplantation (PLT) is negatively impacted by thrombotic and hemorrhagic complications. Limited data exists regarding factors associated with these complications and utilization of anticoagulation. METHODS: Retrospective review of donor, recipient variables and outcomes from four centers participating in the Starzl Network for Excellence in Pediatric Transplantation. RESULTS: 76 PLT included 39 (51%) technical variant transplants, with mean follow-up 628 ± 193.6 days. Median age/weight at transplant were 59.3 ± 53.8 months and 19.6 ± 17.2 kg. Seven (9.2%) transplants experienced intraoperative hepatic artery thrombosis (iHAT), all successfully corrected. Four HAT recurred postoperatively on POD 1,7,8 and 616. All three portal vein thromboses (PVT) occurred on POD1. Anticoagulation protocols were initiated intraoperatively in 50 and postoperatively in 66 and were active for all thrombotic and hemorrhagic events. Two patients were re-transplanted for HAT. Two patients died without having thrombotic or hemorrhagic complications. iHAT and post-operative HAT were associated with lower hepatic arterial flows. iHAT was associated with donor variant anatomy, reduced allografts and intraoperative blood loss. Intraoperative ultrasound could not predict post-operative HAT nor PVT. Surgeon pre-operative concern regarding the native portal vein correlated with postoperative PVT. Lower hepatic arterial and portal flows, higher estimated blood losses, higher prothrombin time and use of arterial interposition grafts were associated with postoperative hemorrhagic complications. CONCLUSIONS: Thrombotic and hemorrhagic complications after pediatric liver transplant remain rare but significant events. Their occurrence can be predicted with pre-operative assessment of donor and recipient vascular anatomy and direct flow measurement but may not be predicted with ultrasound evaluation nor prevented with anticoagulation.

The management of hepatitis B and hepatitis C in children.

In the present paper, we review the increased disease burden of hepatitis B (HBV) and hepatitis C (HCV) infection that is recognized worldwide; especially in children when the most common mode of transmission is vertically from infected mothers. In children with HBV and HCV infection, spontaneous clearance of the virus in the first years of life is not common, in contrast with adults, but these patients often stay asymptomatic until early adulthood, when disease has progressed to chronic hepatitis with increased risk of cirrhosis and its complication, and hepatocellular carcinoma. Due to limited treatment options of HBV infection in the pediatric population, clinicians focus on primary prevention, by vaccinating all infants during their first days of life. Infants born to infected mothers, receive intravenous immunoglobulin on top of the vaccine, and thus preventing transmission in 95% of the infants. While for HCV infection, since there is no vaccine to prevent HCV disease, providers focus primarily on treatment. The treatment landscape of HCV infection in children rapidly evolves, away from interferon regimens, and towards direct-acting antiviral agents that have a safer and more efficacious drug profile. Currently, there are ongoing clinical trials investigating the efficacy and tolerance of direct-acting agents in children below 12 years of age.

Systemic manifestations of extraskeletal myxoid chondrosarcoma associated with a novel t(2;22)(q34;q12) EWS translocation in a child and a review of the literature.

Extraskeletal myxoid chondrosarcoma (EMC), a soft-tissue sarcoma with unique clinicopathologic features and characteristic chromosomal translocations, is extremely rare in the pediatric population. We, herein, present the case of a 7-year-old boy with profound microcytic hypochromic anemia, poor weight gain and a mid-thoracic paraspinal mass that was identified as EMC. Systemic manifestations of localized, nonmetastatic EMC have never been described in the pediatric population, yet our patient's anemia and poor weight gain resolved after successful surgical resection of the tumor, suggesting that localized EMC can present with systemic manifestations. The tumor also contained a novel t(2;22)(q34;q12) translocation involving the EWSR1 gene, which is consistent with additional reports suggesting that a growing list of translocations can drive formation of, and potential new management strategies for, EMC.

Internal Hernia as a Cause for Intestinal Obstruction in a Newborn.

BACKGROUND: An internal hernia is a rare cause of intestinal obstruction, which can occur at any age. Children most often develop an internal hernia due to a congenital defect in the mesentery. While some patients are asymptomatic, others present to medical attention with vague abdominal symptoms, an acute abdomen, or in shock. CASE REPORT: We report a case of a 5-day-old previously healthy baby who presented to our pediatric emergency department with bilious vomiting, grossly bloody stool, and abdominal distention. During an exploratory laparotomy, the patient was diagnosed with an internal hernia caused by a congenital mesenteric defect. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although internal hernia is an infrequent cause of intestinal obstruction in a newborn and requires emergent operative repair, it may be mistaken for other more common causes, such as necrotizing entercolitis, which are often managed medically. This case report aims to highlight some of the difficulties in diagnosis and key features that may assist the clinician in identifying these patients.

Post-transplant eosinophilic gastrointestinal disorders and lymphoproliferative disorder in pediatric liver transplant recipients on tacrolimus.

AIM: To examine and characterize post-transplant eosinophilic gastrointestinal disorders (PTEGID) and post-transplant lymphoproliferative disorder (PTLD) in pediatric liver transplant recipients. METHODS: This is a single center retrospective study of all liver transplant recipients aged 0-18 years from 1999 to 2019 who received tacrolimus as their primary immunosuppressant. Demographic data and clinical/laboratory data including PTEGID, PTLD, liver transplant types, Epstein-Barr virus status, and blood eosinophil count were reviewed. Analysis was done with logistic regression and Mann-Whitney U test. RESULTS: Ninety-eight pediatric liver transplant recipients were included with median age at transplantation of 3.3 years (IQR: 1.1-9.3). The major indication for transplantation was biliary atresia, 51 (52%) cases. Eight (8%) children had PTLD and 14 (14%) had PTEGID. Receiving liver transplantation at an age of ≤1 year was associated with developing PTEGID (OR = 11.9, 95% CI = 3.5-45.6, p < 0.001). Additionally, eosinophilic count of ≥500/µL was associated with having PTLD (OR = 10.7, 95% CI = 1.8-206.0, p = 0.030) as well as having at least one liver rejection (OR = 2.8, 95% CI = 1.2-7.0, p = 0.024). The frequency of food-induced anaphylaxis significantly increased post-transplantation (p = 0.023). CONCLUSIONS: PTEGID and PTLD are common in this cohort and are associated with certain risk factors that help screen children to improve recipient survival. Further studies are needed to evaluate the clinical benefits of these findings.

Efficacy and Tolerance of Blended Diets in Children Receiving Gastrostomy Feeds.

BACKGROUND: To determine the prevalence of gastrointestinal (GI) symptoms in children receiving a blended diet via a gastrostomy tube. METHODS: This is a single-center, retrospective study of children ages 1-18 years that received a blended diet. We reviewed demographics, anthropometrics, clinical characteristics, and rationale for switching to blended diet. Fixed-effects logistic regression analysis was used to evaluate the changes in patient symptoms over the 12-month follow-up period, and fixed-effects regression was employed to test for changes in anthropometrics. RESULTS: Twenty-three patients (8 female, 15 male) were identified, and data from 89 outpatient visits were analyzed. The most common underlying diagnosis was neurological disorder. Thirty-five percent of patients received commercial whole cow milk formulas, 30% received hydrolysate formulas, and 35% received amino acid-based formulas. After formula switches were made, 65% received homemade blended diets, 17.5% received commercial blended diets, and 17.5% received a combination of both. Median duration of time on a blended diet was 17 months. Ninety-five percent of patients who were previously experiencing upper GI symptoms improved within the first 3 months after blended diet initiation. Twenty-one percent of patients developed mild constipation on the diet, which was managed with increased water intake and/or polyethylene glycol. Only 2 patients discontinued the blended diet, because of inadequate weight gain and worsening of upper GI symptoms. CONCLUSIONS: In our study population, blended diets were well tolerated in gastrostomy-fed children and were associated with clinical improvement of upper GI symptoms.