Preclinical, randomized phase 1, and compassionate use evaluation of REGN4461, a leptin receptor agonist antibody for leptin deficiency.

Deficiency in the adipose-derived hormone leptin or leptin receptor signaling causes class 3 obesity in individuals with genetic loss-of-function mutations in leptin or its receptor LEPR and metabolic and liver disease in individuals with hypoleptinemia secondary to lipoatrophy such as in individuals with generalized lipodystrophy. Therapies that restore leptin-LEPR signaling may resolve these metabolic sequelae. We developed a fully human monoclonal antibody (mAb), REGN4461 (mibavademab), that activates the human LEPR in the absence or presence of leptin.

Feasibility of using a patient-reported outcome measure into clinical practice following pediatric liver transplantation: The Starzl Network experience.

Background: Patient-reported outcome measures (PROMs) are not routinely used in clinical care by pediatric liver transplant (LT) teams. The Starzl Network for Excellence in Pediatric Transplantation (SNEPT) assessed feasibility of using a disease-specific Quality of Life (QoL) questionnaire in the ambulatory setting at 10 SNEPT sites.

Methods: A mixed methods feasibility project assessing administration processes, barriers, and user experiences with the Pediatric Liver Transplant Quality of Life (PeLTQL) tool.

Living Donor Liver Transplantation vs. Split Liver Transplantation Using Left Lateral Segment Grafts in Pediatric Recipients: An Analysis of the UNOS Database.

Split and LDLT in pediatric patients have the potential to decrease wait times and waitlist mortality. Using UNOS-STAR data, we compared outcomes of pediatric patients undergoing LDLT and SLT using LLS grafts. The baseline characteristics and post-operative outcomes were compared between groups.

Increased use of split liver grafts in adult recipients following implementation of a pediatric liver transplant program.

Background: Split liver transplantation (SLT) is a strategy to address organ shortage, but is a technically more demanding procedure than whole graft liver transplantation (LT). We aimed to determine the outcomes following SLT in adult recipients as well as to highlight the impact that having a pediatric LT program has on SLT implementation.

Methods: All SLTs conducted at a single-center from 2010 to 2019 were identified.

Incidence and Sequelae of Liver Injury Among Children Treated for Solid Tumors: Analysis of a Large Single-Center Prospective Cohort.

Objectives: Pediatric oncology patients are at risk of adverse drug events. The incidence and etiologies of liver injury in this population are not well characterized. We utilized a large, single-center pediatric oncology registry to investigate the incidence, causes, and outcomes of liver injury during treatment for solid tumor malignancies.

The complicated clinical course in a case of atypical lipodystrophy after development of neutralizing antibody to metreleptin: treatment with setmelanotide.

Summary: A patient with atypical partial lipodystrophy who had a transient initial response to metreleptin experienced acute worsening of her metabolic state when neutralizing antibodies against metreleptin appeared. Because her metabolic status continued to deteriorate, a therapeutic trial with melanocortin-4 receptor agonist setmelanotide, that is believed to function downstream from leptin receptor in the leptin signaling system, was undertaken in an effort to improve her metabolic status for the first time in a patient with lipodystrophy. To achieve this, a compassionate use (investigational new drug application; IND) was initiated (NCT03262610).

Congenital Portosystemic Shunts in Children: Associations, Complications, and Outcomes.

Background: Congenital portosystemic shunt (CPSS) is a rare malformation in which splanchnic venous flow bypasses the liver. CPSS is associated with other congenital anomalies and syndromes and can be associated with life-threatening complications. CPSS and their management remain underreported in the literature.

Prospective Assessment of Ultrasound Shear Wave Elastography for Discriminating Biliary Atresia from other Causes of Neonatal Cholestasis.

Objective: To prospectively assess the diagnostic performance of ultrasound shear wave elastography (SWE) and hepatobiliary laboratory biomarkers for discriminating biliary atresia from other causes of neonatal cholestasis.

Study Design: Forty-one patients <3 months of age with neonatal cholestasis (direct bilirubin >2 mg/dL) and possible biliary atresia were prospectively enrolled. Both 2-dimensional (2D) and point ultrasound SWE were performed prior to knowing the final diagnosis.

Antimicrobials and Antiepileptics Are the Leading Causes of Idiosyncratic Drug-induced Liver Injury in American Children.

Objectives: The aim of this study was to provide an overview of the presenting features, etiologies, and outcomes of children enrolled in the Drug-induced Liver Injury Network (DILIN) prospective and retrospective studies.

Methods: Consecutive definite, highly likely, or probable cases in children enrolled into the ongoing DILIN prospective and retrospective studies between September 2004 and February 2017 were reviewed.

Results: Fifty-seven cases were adjudicated as definite (14), highly likely (30), or probable (13) DILI.

Spectrum of disease associated with partial lipodystrophy: lessons from a trial cohort.

Context: Partial lipodystrophy (PL) is associated with metabolic co-morbidities but may go undiagnosed as the disease spectrum is not fully described.

Objective: The objective of the study was to define disease spectrum in PL using genetic, clinical (historical, morphometric) and laboratory characteristics.

Design: Cross-sectional evaluation.

Effect of Fontan operation on liver stiffness in children with single ventricle physiology.

Objectives: Assess liver stiffness using ultrasound point shear wave elastography (US P-SWE) in children before and after the Fontan operation.

Methods: Eighteen children undergoing the Fontan operation were prospectively enrolled. Eight US P-SWE measurements were obtained from the right hepatic lobe before surgery, and at multiple postoperative time points.

Identification of intramural epithelial networks linked to peribiliary glands that express progenitor cell markers and proliferate after injury in mice.

Unlabelled: Peribiliary glands (PBGs) are clusters of epithelial cells residing in the submucosal compartment of extrahepatic bile ducts (EHBDs). Though their function is largely undefined, they may represent a stem cell niche. Here, we hypothesized that PBGs are populated by mature and undifferentiated cells capable of proliferation in pathological states.

The VEGF receptor flt-1 (VEGFR-1) is a positive modulator of vascular sprout formation and branching morphogenesis.

Sprouting angiogenesis is critical to blood vessel formation, but the cellular and molecular controls of this process are poorly understood. We used time-lapse imaging of green fluorescent protein (GFP)-expressing vessels derived from stem cells to analyze dynamic aspects of vascular sprout formation and to determine how the vascular endothelial growth factor (VEGF) receptor flt-1 affects sprouting. Surprisingly, loss of flt-1 led to decreased sprout formation and migration, which resulted in reduced vascular branching.