ArticleJournal of pediatric gastroenterology and nutrition2020
Activated CD8 T-cell Hepatitis in Children With Indeterminate Acute Liver Failure: Results From a Multicenter Cohort.
Article in Journal of pediatric gastroenterology and nutrition, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Characterization of a Hepatitis Outbreak in Children, 2021 to 2022.JAMA network open · 2022Pooled it
- Immune mechanisms and pathophysiology of T cell-mediated pediatric acute liver failure (TC-PALF).Hepatology communications · 2026Review
- CD8 TRM-like T cells expressing perforin and IFN-γ define a pediatric activated T-cell acute liver failure endotype.Hepatology communications · 2026Article
- Contaminating plasmid sequences and disrupted vector genomes in the liver following adeno-associated virus gene therapy.Nature medicine · 2026Article
- Acute severe cholestatic hepatitis and lymphopenia characterize pediatric hepatitis-associated aplastic anemia.Journal of pediatric gastroenterology and nutrition · 2026Article
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- Article
- Origins of T-cell-mediated autoimmunity in acquired aplastic anaemia.British journal of haematology · 2025Review
- Expansion of CD103Frontiers in immunology · 2025Article
- Anti-Thymocyte Globulin Treatment of Steroid-Refractory T-Cell Hepatitis in Children: A Case Series.Gastro hep advances · 2025Review
- Identification of pediatric activated T-cell hepatitis using clinical immune studies.Clinics and research in hepatology and gastroenterology · 2024Article
- Immunosuppression in two cases of indeterminate hepatitis.Canadian liver journal · 2024Article
- Adenovirus is Not Detected in Liver Tissue From a Historical Multicenter Cohort of Children With Acute Liver Failure.Journal of pediatric gastroenterology and nutrition · 2023Article
- Recent Increase in Incidence of Severe Acute Hepatitis of Unknown Etiology in Children is Associated with Infection with Adenovirus and Other Nonhepatotropic Viruses.The Journal of pediatrics · 2023Article
- Acute hepatitis of unknown aetiology in children: a clinical update on the recent outbreak with mechanistic insights.Clinical and experimental immunology · 2023Review
- Effector memory CD8 T-cells as a novel peripheral blood biomarker for activated T-cell pediatric acute liver failure.PloS one · 2023Article
- Orchestrated regulation of immune inflammation with cell therapy in pediatric acute liver injury.Frontiers in immunology · 2023Review
- Immunological characteristics of severe acute hepatitis of unknown origin in a child post SARS-CoV-2 infection.Clinical immunology (Orlando, Fla.) · 2022Article
- Familial hemophagocytic lymphohistiocytosis hepatitis is mediated by IFN-γ in a predominantly hepatic-intrinsic manner.PloS one · 2022Article
- Acute severe hepatitis outbreak in children: A perfect storm. What do we know, and what questions remain?Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 1 country.
Funding
Abstract
objectivesIn many pediatric acute liver failure (PALF) cases, a diagnosis is not identified, and the etiology is indeterminate (IND-PALF). Our pilot study found dense CD8 T-cell infiltrates and increased T-cell clonality in liver specimens from IND-PALF patients. We aimed to validate these findings in a multicenter cohort with investigators blinded to diagnosis.
methodsPALF Study Group registry subjects with IND-PALF (n = 37) and known diagnoses (DX-PALF) (n = 18), ages 1 to 17 years, with archived liver tissue were included. Liver tissue slides were stained for T cells (CD8 and CD4), B cells (CD20), macrophages (CD163), perforin, and tissue resident-memory T cells (Trm, CD103), and scored as minimal, moderate, or dense. Lymphocytes were isolated from frozen liver tissue for T-cell receptor beta (TCRβ) sequencing.
resultsDense hepatic CD8 staining was found in significantly more IND-PALF (n = 29, 78%) compared with DX-PALF subjects (n = 5, 28%) (P = 0.001). IND-PALF subjects were more likely to have dense or moderate perforin (88% vs 50%, P = 0.03) and CD103 (82% vs 40%, P = 0.02) staining compared with DX-PALF subjects. TCRβ sequencing of 15 IND-PALF cases demonstrated increased clonal overlap compared with 6 DX-PALF cases (P = 0.002).
conclusionsDense infiltration of effector Trm CD8 T cells characterizes liver tissue from IND-PALF subjects. Increased clonality suggests the T-cell expansion is antigen(s)-driven as opposed to a nonspecific inflammatory response. These findings support CD8 staining as a new biomarker of the activated CD8 T-cell PALF phenotype. Future studies are needed to characterize potential antigens, host risk factors, and inflammatory pathways with the goal of developing targeted therapies.
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