Education and Psychosocial Factors Predict Odds of Death After Transfer to Adult health Care in Pediatric Liver Transplant Patients.

OBJECTIVES: To analyze demographic, psychosocial, and clinical factors in pediatric liver transplant recipients for their association with death or loss to follow up in adulthood. We aimed to better understand known health disparities in transplant outcomes and identify potentially modifiable risk factors prior to transfer. METHODS: A retrospective cohort study of children who underwent liver transplantation at a large tertiary transplant center and were transferred to adult care between 2000 and 2015. RESULTS: During the study period, 101 qualifying patients were transferred. Ninety-three individuals followed with an adult provider, while 8 were lost to follow up. In total 23 of 93 patients died after transfer (24.7%). Several childhood factors were associated with adult death: Black race [odds ratio (OR) 6.59, P < 0.001]; psychiatric illness or substance use (OR 2.81, P = 0.04); failure to graduate high school before transfer (OR 9.59, P < 0.001); posttransplant tacrolimus medication-level variability index >2.5 (OR 5.36, P = 0.04); provider documentation of medication nonadherence (OR 4.72, P = 0.02); acute cellular rejection (OR 4.44, P = 0.03); the presence of diabetes mellitus (OR 5.71, P = 0.001), and chronic kidney disease (OR 2.82, P = 0.04). Failure to graduate HS was associated with loss to follow up ( P < 0.001). On multivariate analysis, Black race, substance use, diabetes, and failure to graduate HS retained association with adult death (each P < 0.05). CONCLUSIONS: Complex, intertwined patient characteristics are associated with increased odds of death in pediatric liver transplant recipients transferred to adult care. Early recognition of high-risk patients and intervention for modifiable factors, such as improved HS graduation and substance use prevention, may improve long-term outcomes.

Resolution of recurrent pediatric acute liver failure with liver transplantation in a patient with NBAS mutation.

BACKGROUND: Pediatric acute liver failure (PALF) remains an enigmatic process of rapid end-organ dysfunction associated with a variety of pathologic conditions though the predominant cause is indeterminate. A growing body of research has identified mutations in the NBAS gene to be associated with recurrent acute liver failure and multi-systemic disease including short stature, skeletal dysplasia, facial dysmorphism, immunologic abnormalities, and Pelger-Huët anomaly. METHODS AND RESULTS: Here, we describe a 4-year-old girl who presented with dehydration in the setting of acute gastroenteritis and fever but went on to develop PALF on day 2 of hospitalization. She clinically recovered with supportive measures, but after discharge, had at least 2 additional episodes of PALF. Ultimately, she underwent liver transplant and her recurrent episodes of PALF did not recur throughout a 6-year follow-up period. Whole-exome sequencing post-liver transplant initially revealed two variants of uncertain significance in the NBAS gene. Parental studies confirmed the c.1549C > T(p.R517C; now likely pathogenic) variant from her mother and a novel c.4646T > C(p.L1549P) variant from her father. In silico analyses predicted these variants to have a deleterious effect on protein function. Consistent with previously characterized NBAS mutation-associated disease (NMAD), our patient demonstrated the following features: progeroid facial features, hypoplasia of the 12th ribs, Pelger-Huët anomaly on peripheral blood smear, and abnormal B and NK cell function. CONCLUSION: Altogether, we describe a novel pathogenic variant in the NBAS gene of a patient with NMAD and report the resolution of recurrent PALF secondary to NMAD following liver transplantation.

Development and repair of aorto-esophageal fistula following esophageal button battery impaction: A case report.

BACKGROUND: Complications from esophageal button battery impactions remain a real fear for practicing pediatric gastroenterologists and surgeons. This case describes a child who developed an aorto-esophageal fistula 25 days after initial battery ingestion and survived due to prompt placement of an aortic stent via minimally invasive surgery, avoiding an open procedure. CASE PRESENTATION: A 6-year-old female presented acutely with a mid-esophageal button battery impaction witnessed by her parents. Presenting symptoms included chest pain and emesis. Button battery location and size were confirmed on X-ray. She underwent removal with flexible esophagogastroduodenoscopy (EGD) and rigid esophagoscopy. She was admitted to the hospital and received conservative medical management, with serial cross-sectional imaging via chest MRIs to assess the evolution of her injury according to available national guidelines, and was discharged after 12 days of close inpatient monitoring. Despite these measures the patient represented 25 days post-ingestion with hematemesis from a new aorto-esophageal fistula, requiring emergent cardiac catheterization with successful, life-saving aortic stent placement. She remained admitted for an additional 12 days of monitoring as her diet was advanced slowly post-catheterization. Since this second hospitalization she continues to do well, with outpatient follow-up by multiple subspecialists. CONCLUSIONS: This case highlights the continued uncertainty regarding the risk of developing this complication, as well as gaps in the current literature and guidelines for managing these patients following ingestion and esophageal injury. It also details the unique course following development of this complication and its surgical repair.

African American Pediatric Liver Transplant Recipients Have an Increased Risk of Death After Transferring to Adult Healthcare.

OBJECTIVE: To analyze the long-term outcomes in pediatric liver transplant recipients after they have transferred to an adult provider and assess for racial disparities in health outcomes. STUDY DESIGN: This is a single-center, retrospective review of pediatric patients who underwent liver transplantation between July 1990 and August 2015 at a tertiary healthcare system with a large transplant center. Patient mortality and retransplantation were assessed after transfer to adult care. RESULTS: There were 120 patients who were transferred, of whom 19 did not meet the inclusion criteria. Of the remaining 101 patients, 64 (63%) transferred care to a nearby affiliated tertiary adult facility, 29 (29%) were followed by other healthcare systems, and 8 (8%) were lost to follow-up. Of the patients followed at our affiliated adult center, 18 of the 64 (28%) died. Of those 18 deaths, 4 (22%) occurred within the first 2 years after transfer, and 10 (55%) within 5 years of transfer. Four patients were retransplanted by an adult provider, of whom 2 eventually received a third transplant. African Americans had higher rates of death after transfer than patients of other races (44% mortality vs 16%, representing 67% of all cases of death; P = .032), with nearly 50% mortality at 20 years from time of transplantation. CONCLUSIONS: Death is common in pediatric liver transplant recipients after transfer to adult care, with African Americans having disproportionately higher mortality. This period of transition of care is a vulnerable time, and measures must be taken to ensure the safe transfer of young adults with chronic health care needs.

Undiagnosed Metachromatic Leukodystrophy Presenting as Severe Gastrointestinal Bleeding and Cholestasis from Hemobilia.

Metachromatic leukodystrophy (MLD) is a neurodegenerative disorder caused by the accumulation of lipids called sulfatides throughout the nervous system. Sulfatides can also collect in other organs throughout the body including the gallbladder where they form polyps. Gallbladder polyps rarely have been found to bleed in patients with known MLD, presumably due to polyp shearing. Here we present a case of a child with autism presenting with severe gastrointestinal bleeding and direct hyperbilirubinemia, requiring significant resuscitation and biliary drain placement to tamponade ongoing bleeding. Subsequent neurologic and genetic investigation led to the diagnosis of MLD, with laparoscopic cholecystectomy revealing extensive, elongated gallbladder polyps. Clinicians who care for patients with MLD, including gastroenterologists who manage their progressive oropharyngeal dysphagia, should be aware of the risk for this life-threatening complication. Moreover, pediatric gastroenterologists and hepatologists should maintain a high index of suspicion for MLD in new patients presenting with developmental regression and gastrointestinal bleeding.

Performance of Interferon-Gamma Release Assays for Tuberculosis Screening in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: The aim of the study was to analyze the diagnostic accuracy and utility of QuantiFERON-TB Gold In-Tube, an interferon-gamma release assay (IGRA), as a screening tool for latent tuberculosis infection (LTBI) in pediatric patients with inflammatory bowel disease (IBD) undergoing treatment with anti-tumor necrosis factor (anti-TNF) medications. To describe cases of tuberculosis in the pediatric IBD population, TB treatment courses, outcomes, and their effect on IBD management. METHODS: A single-center, retrospective cohort study of pediatric IBD patients who underwent tuberculosis screening. IGRA testing from 2011 to 2017 were analyzed to determine result rates, characteristics, and outcomes. RESULTS: One thousand seven hundred fifty-four (1,754) tests were performed on 859 patients. One thousand six hundred thirty-four (1,634) tests were negative, 9 were positive, and 111 were indeterminate. Eight of 9 positive tests resulted during repeat annual screening while receiving IBD treatment. Five patients were treated for latent tuberculosis infection (LTBI), and 4 were false-positives. IBD therapy was interrupted in 3 patients, with no negative long-term outcomes. We report 1 known false-negative, in a patient who developed disseminated TB on anti-TNF therapy. Indeterminate testing rates were higher at IBD diagnosis than during treatment (10.3% vs 5.3%, P < 0.001). Follow-up testing of indeterminate results was negative in all patients retested, with 14 patients lost to follow-up. No patient with indeterminate testing developed TB. CONCLUSIONS: IGRAs are a useful tool to screen for LTBI, both before anti-TNF therapy and during treatment. Results should be used in concert with detailed history and examination. Positive and indeterminate results should be promptly repeated for timely TB diagnosis and to minimize interruptions in IBD therapy.