Identification of pediatric activated T-cell hepatitis using clinical immune studies.

Background And Aims: The majority of indeterminate pediatric acute liver failure (PALF) cases are secondary to immune dysregulation, labeled activated T-cell hepatitis (TCHep). We aimed to describe a cohort of children with acute severe hepatitis and PALF and define how clinical immune labs may help identify the TCHep group.

Methods: Retrospective review of children with acute hepatitis and PALF between March 2020 and August 2022.

Utilization and perspectives of weight loss medications in pediatric metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing globally in pediatric populations. Currently, MASLD management primarily relies on lifestyle interventions, which pose challenges in sustaining long-term weight loss. This study investigated the use of weight loss medications in MASLD care through an international survey of 166 pediatric gastroenterologists and hepatologists.

CXCL9 inhibition does not ameliorate disease in murine models of both primary and secondary hemophagocytic lymphohistiocytosis.

Hemophagocytic Lymphohistiocytosis (HLH) is a group of disorders culminating in systemic inflammation and multi-organ failure with high incidence of hepatic dysfunction. Overproduction of IFN-γ is the main immunopathological driver in this disorder. Monokine induced by IFN-γ (CXCL9) serves as a biomarker for disease activity and response to treatment in this disorder.

Effector memory CD8 T-cells as a novel peripheral blood biomarker for activated T-cell pediatric acute liver failure.

A distinct phenotype of pediatric acute liver failure (PALF) has been identified, labeled activated T-cell hepatitis. These patients, previously included within the indeterminate group, have evidence of systemic immune activation and liver biopsy specimens with dense infiltration of CD8+ T-cells. We aimed to evaluate the peripheral blood T-cell phenotype in PALF patients with activated T-cell hepatitis compared to indeterminate cause.

Adenovirus is Not Detected in Liver Tissue From a Historical Multicenter Cohort of Children With Acute Liver Failure.

There has been a recent surge in cases of pediatric acute hepatitis and pediatric acute liver failure (PALF) of unknown cause. Several reports have described clusters of these children who were positive for adenovirus (AdV) DNA, primarily in peripheral blood but some in liver tissue. We tested archived liver tissue specimens from a historical cohort of 44 children with PALF who were enrolled in a multicenter biorepository between 2007 and 2014 for AdV 40/41 using quantitative polymerase chain reaction.

The Liver in Hemophagocytic Lymphohistiocytosis: Not an Innocent Bystander.

Hemophagocytic lymphohistiocytosis (HLH) is a rare multisystemic hyperinflammatory disease commonly associated with hepatic dysfunction. Liver injury is mediated by unchecked antigen presentation, hypercytokinemia, dysregulated cytotoxicity by natural killer and CD8 T cells, and disruption of intrinsic hepatic metabolic pathways. Over the past decade, there have been significant advances in diagnostics and expansion in therapeutic armamentarium for this disorder allowing for improved morbidity and mortality.

The RAG1 Ubiquitin Ligase Domain Stimulates Recombination of TCRβ and TCRα Genes and Influences Development of αβ T Cell Lineages.

RAG1/RAG2 (RAG) endonuclease-mediated assembly of diverse lymphocyte Ag receptor genes by V(D)J recombination is critical for the development and immune function of T and B cells. The RAG1 protein contains a ubiquitin ligase domain that stabilizes RAG1 and stimulates RAG endonuclease activity in vitro. We report in this study that mice with a mutation that inactivates the Rag1 ubiquitin ligase in vitro exhibit decreased rearrangements and altered repertoires of TCRβ and TCRα genes in thymocytes and impaired thymocyte developmental transitions that require the assembly and selection of functional TCRβ and/or TCRα genes.

Familial hemophagocytic lymphohistiocytosis hepatitis is mediated by IFN-γ in a predominantly hepatic-intrinsic manner.

Interferon gamma (IFN-γ) is the main cytokine driving organ dysfunction in Familial Hemophagocytic Lymphohistiocytosis (FHL). Blockade of IFN-γ pathway ameliorates FHL hepatitis, both in animal models and in humans with FHL. Hepatocytes are known to express IFN-γ receptor (IFN-γ-R).

Severe Hepatitis in Pediatric Coronavirus Disease 2019.

Hepatic involvement in coronavirus disease 2019 (COVID-19) is typically characterized as mild hepatitis with preserved synthetic function in children. Severe hepatitis is a rare complication of COVID-19 infection that has not been extensively described in the pediatric population. We report a case series of four previously healthy children who presented with significant hepatitis as the primary manifestation of COVID-19 infection.

Live Vaccines in Pediatric Liver Transplant Recipients: "To Give or Not to Give".

Content available: Author Audio Recording.

Hepatic Ciliopathy Syndromes.

Content available: Author Interview and Audio Recording.

Nutrition rehabilitation-related complications in primary mitochondrial disorders.

Primary mitochondrial disorders (PMDs) comprise a group of hundreds of individual genetic diseases affecting mitochondrial function, including oxidative phosphorylation and energy production. The estimated prevalence of these disorders ranges from 2.9 to 20 cases per 100,000.

A new syndrome of moyamoya disease, kidney dysplasia, aminotransferase elevation, and skin disease associated with de novo variants in RNF213.

Ring-finger protein 213 (RNF213) encodes a protein of unknown function believed to play a role in cellular metabolism and angiogenesis. Gene variants are associated with susceptibility to moyamoya disease. Here, we describe two children with moyamoya disease who also demonstrated kidney disease, elevated aminotransferases, and recurrent skin lesions found by exome sequencing to have de novo missense variants in RNF213.