Maralixibat Reduces Serum Bile Acids and Improves Cholestatic Pruritus in Adolescents With Alagille Syndrome.

Background: Alagille syndrome (ALGS) is a multisystem cholestatic disorder. Maralixibat is approved for the treatment of cholestatic pruritus in ALGS with limited data in adults.

Methods: Participants were included if they received ≥ 2 doses of maralixibat at age ≥ 16 years in one of the three previously published maralixibat ALGS clinical trials.

COVID-19 vaccination induces distinct T-cell responses in pediatric solid organ transplant recipients and immunocompetent children.

Immune responses to COVID-19 vaccination are attenuated in adult solid organ transplant recipients (SOTRs) and additional vaccine doses are recommended for this population. However, whether COVID-19 mRNA vaccine responses are limited in pediatric SOTRs (pSOTRs) compared to immunocompetent children is unknown. Due to SARS-CoV-2 evolution and mutations that evade neutralizing antibodies, T cells may provide important defense in SOTRs who mount poor humoral responses.

Liver transplant for primary biliary tract neuroendocrine tumor in a nine-year-old girl.

Background: Neuroendocrine tumors (NETs) are rare epithelial neoplasms that arise most commonly from the gastrointestinal tract. In pediatrics, the most common site of origin is in the appendix, with the liver being the most common site of metastasis. Neuroendocrine tumors arising from the biliary tract are extremely rare.

Anti-spike antibody durability after SARS-CoV-2 vaccination in adolescent solid organ transplant recipients.

Background: Adolescent solid organ transplant recipients (aSOTRs) who received three doses of the COVID-19 mRNA vaccine experience high seroconversion rates and antibody persistence for up to 3 months. Long-term antibody durability beyond this timeframe following three doses of the SARS-CoV-2 mRNA vaccine remains unknown. We describe antibody responses 6 months following the third vaccine dose (D3) of the BNT162b2 mRNA vaccination among aSOTRs.

Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA.

Background And Aims: Alagille syndrome (ALGS) is characterized by chronic cholestasis with associated pruritus and extrahepatic anomalies. Maralixibat, an ileal bile acid transporter inhibitor, is an approved pharmacologic therapy for cholestatic pruritus in ALGS. Since long-term placebo-controlled studies are not feasible or ethical in children with rare diseases, a novel approach was taken comparing 6-year outcomes from maralixibat trials with an aligned and harmonized natural history cohort from the G lobal AL agille A lliance (GALA) study.

Trends in the Utilization of Herbal and Dietary Supplements in Patients with Chronic Liver Disease During the SARS-CoV2 Pandemic.

Background: We studied the pattern of herbal and dietary supplement (HDS) use in patients with chronic liver disease (CLD) during the first year of the COVID-19 pandemic.

Methods: A questionnaire/survey was sent to hepatology patients with CLD under the care of hepatologists at Johns Hopkins University School of Medicine.

Results: The 5 most taken dietary supplements during the pandemic included vitamin B12 (27.

Change in Health-Related Quality of Life in Youth with Chronic Hepatitis B Living in North America: A 5-Year Cohort Study.

Background: Greater hepatitis-related symptomology is associated with lower health-related quality-of-life (HRQoL) among untreated youth with chronic hepatitis B (CHB). How HRQoL changes over time in this population is unknown.

Methods: Children from 7 hepatology centers in North America positive for hepatitis B surface antigen, not taking anti-viral therapy, were enrolled in the Hepatitis B Research Network.

Predictors of 6-year event-free survival in Alagille syndrome patients treated with maralixibat, an ileal bile acid transporter inhibitor.

Background And Aims: Refractory pruritus and other complications of cholestasis are indications for liver transplantation (LT) in patients with Alagille syndrome (ALGS). We evaluated predictors of event-free survival and transplant-free survival in patients with ALGS treated with maralixibat (MRX), an ileal bile acid transporter inhibitor.

Approach And Results: We assessed patients with ALGS from 3 clinical trials of MRX with up to 6 years of follow-up.

Costs of pediatric liver transplantation among commercially insured and Medicaid-insured patients with cholestasis in the US.

Children with rare cholestatic liver diseases, such as Alagille syndrome, progressive familial intrahepatic cholestasis, and biliary atresia typically require liver transplantation (LT). The objective of this analysis was to assess the economic burden of LT on these patients. Health care resource utilization and costs associated with pediatric LT were retrospectively assessed using insurance claims data from the US IBM MarketScan Commercial and Medicaid databases collected between October 2015 and December 2019.

Health Care Resource Utilization by Patients with Alagille Syndrome.

Objective: To assess and characterize health care resource utilization (HRU) in children with the rare, genetic, multisystem disorder, Alagille syndrome.

Study Design: This retrospective analysis reviewed commercially insured and Medicaid-insured claims from October 1, 2015 to December 31, 2019 to assess HRU in patients with Alagille syndrome. As there is no specific International Classification ofDiseases-10 code for Alagille syndrome, patients were identified using the following algorithm: ≥1 claim with diagnosis code Q44.

Endoluminal Functional Lumen Imaging Probe Is Safe in Children Under Five Years Old.

Background: Endoluminal functional lumen imaging probe (EndoFLIP) is a minimally invasive, novel device that uses high-resolution impedance planimetry to measure important parameters of the gastrointestinal lumen that aid in the diagnosis of esophageal disorders. EndoFLiP is approved by the US Food and Drug Administration (FDA) for children 5 years and older. We sought to compare its safety and luminal characteristics between children under 5 years of age with children 5 years and older.

Survival Benefit of Split-Liver Transplantation for Pediatric and Adult Candidates.

Patient and graft survival are similar following whole-liver transplantations (WLTs) versus split-liver transplantations (SLTs) among pediatric and adult recipients, yet SLTs are rarely used. We sought to determine the survival benefit associated with accepting a splittable graft offer for SLT versus declining and waiting for a subsequent offer using 2010 to 2018 Scientific Registry of Transplant Recipients (SRTR) data on 928 pediatric and 1814 adult liver transplantation candidates who were ever offered a splittable graft. We compared eventual mortality, regardless of subsequent transplants, between those patients who accepted versus declined a split liver offer with adjustments for Pediatric End-Stage Liver Disease/Model for End-Stage Liver Disease (MELD) scores, diagnosis, and weight among pediatric candidates and matching for MELD score, height, and offer among adult candidates.

Hepatitis B e antigen loss in adults and children with chronic hepatitis B living in North America: A prospective cohort study.

Hepatitis B e antigen (HBeAg) is a soluble viral protein in plasma of patients with hepatitis B virus infection. HBeAg loss is an important first stage of viral antigen clearance. We determined the rate and predictors of HBeAg loss in a North American cohort with chronic hepatitis B viral infection (CHB).

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.

The Inflammatory Cytokine Profile Associated With Liver Damage Is Broader and Stronger in Patients With Chronic Hepatitis B Compared to Patients With Acute Hepatitis B.

Liver damage in hepatitis B is immune driven and correlates with inflammatory markers in patient serum. There is no comparison of these markers to determine if inflammatory profiles are distinct to different types of liver damage across patients at different stages of disease. We measured 25 inflammatory markers in patients with acute hepatitis B and chronic hepatitis B with hepatitis B e antigen seroconversion and chronic patients stopping nucleoside analogue therapy.

Chronic Hepatitis Is Common and Often Untreated Among Children with Hepatitis B Infection in the United States and Canada.

Objective: To determine the outcomes of chronic hepatitis B virus (HBV) infection in a large, prospectively studied cohort of children in the US and Canada.

Study Design: This was a prospective, observational study of children with chronic HBV enrolled in 7 clinical centers and evaluated at baseline, weeks 24 and 48, and annually thereafter, with analysis of demographic, clinical, physical examination, and blood test data.

Results: Among 362 children followed for a median of 4.

Recurrence of Primary Sclerosing Cholangitis After Liver Transplant in Children: An International Observational Study.

Background And Aims: Recurrent primary sclerosing cholangitis (rPSC) following liver transplant (LT) has a negative impact on graft and patient survival; little is known about risk factors for rPSC or disease course in children.

Approach And Results: We retrospectively evaluated risk factors for rPSC in 140 children from the Pediatric PSC Consortium, a multicenter international registry. Recipients underwent LT for PSC and had >90 days of follow-up.

Stimulating Solutions for Intractable Epilepsy.

Implantable devices for controlling medically intractable seizures nondestructively are rapidly advancing. These offer reversible, potentially, restorative options beyond traditional, surgical procedures, which rely, largely on resection or ablation of selected brain sites. Several lines of, investigation aimed at improving efficacy of these devices are discussed, ranging from identifying novel subcortical, white matter, or cell-type specific targets to engineering advances for adaptive techniques based- on continuous, dynamic system analysis.

Clinical significance of quantitative e antigen in a cohort of hepatitis B virus-infected children and adults in North America.

Background: In chronic hepatitis B (CHB) viral infection, e antigen positivity (HBeAg+) is associated with high levels of viral replication and infectivity. Furthermore, HBeAg-positive CHB is associated with a liver disease spectrum ranging from none to severe.

Aim: To assess whether the level of circulating HBeAg is associated with different clinical presentations of HBeAg-positive CHB.

Liver simulated allocation model does not effectively predict organ offer decisions for pediatric liver transplant candidates.

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.