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Immune mechanisms and pathophysiology of T cell-mediated pediatric acute liver failure (TC-PALF)

Year: 2026

Type: article

Abstract: Immune dysregulation in pediatric acute liver failure (PALF) is a distinct phenomenon that has garnered interest with respect to disease outcomes and targeted therapies. Some patients with PALF have an "indeterminate" (iPALF) etiology ranging from acute severe hepatitis to fulminant liver failure. Recent evidence from iPALF demonstrates that a large subset suffers from a unified, immune-mediated disorder. This immune-mediated PALF has been defined by the presence of dense T-cell infiltrates on liver biopsy and is often referred to as T-cell PALF (TC-PALF). TC-PALF has common features with other inflammatory liver diseases, including autoimmune hepatitis, hemophagocytic lymphohistiocytosis, and macrophage activation syndrome, while also demonstrating distinct pathologic features that contribute to liver injury in PALF. In this review, the spectrum of disease, comparisons between young and aged liver immune microenvironments, and the current literature evaluating the immune system during PALF are summarized. Relationships between TC-PALF, other inflammatory liver diseases, and contemporary studies that associate specific immune subsets with this pathology are also reviewed. These studies use precision "omic" technologies to investigate tissue and blood samples in TC-PALF and have opened new lines of investigation into potential genetic, immunologic, and environmental risk factors for disease. Together, recent data suggest that immune dysregulation is a central feature of TC-PALF, and facets of disease offer potential biomarker identification to aid in the clinical management of TC-PALF.

Source: Hepatology Communications

DOI: 10.1097/hc9.0000000000001033