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

Authors

Jason T C Lee, Harry Sutton, Priya Pai, Arianna Barbetta, Shengmei Zhou, Rohit Kohli, Sonya MacParland, Juliet Emamaullee

Published in

Hepatology communications. Volume 10. Issue 9. Sep 01, 2026. Epub Aug 20, 2026.

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.

PMID:
42623522
Bibliographic data and abstract were imported from PubMed on 21 Aug 2026.

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