Identification of pediatric activated T-cell hepatitis using clinical immune studies - 29/06/24
, Tamir Diamond c, d, 1, ⁎ , Adriana Perez d, Portia A Kreiger e, f, Kathleen M Loomes c, d, Edward M Behrens c, g, Estella M Alonso a, bHighlights |
• | Many cases of acute hepatitis and liver failure in children are of unknown cause. |
• | These children often have features of immune dysregulation, labeled activated T-cell hepatitis (TC-hep). |
• | Clinically available peripheral blood immune studies can help identify the TC-hep group. |
• | TC-hep patients have increased markers of CD8 T-cell activation, proliferation, and cytotoxic function. |
• | Workup of children with liver failure of unknown cause should be standardized to include immune dysregulation evaluation. |
Abstract |
Background and aims |
The majority of indeterminate pediatric acute liver failure (PALF) cases are secondary to immune dysregulation, labeled activated T-cell hepatitis (TC-Hep). We aimed to describe a cohort of children with acute severe hepatitis and PALF and define how clinical immune labs may help identify the TC-Hep group.
Methods |
Retrospective review of children with acute hepatitis and PALF between March 2020 and August 2022. Patients were classified as known diagnosis, indeterminate hepatitis (IND-Hep), or TC-Hep (defined by liver biopsy with predominant CD8 T-cell inflammation or development of aplastic anemia).
Results |
124 patients were identified: 83 with known diagnoses, 16 with TC-Hep, and 25 with IND-Hep. Patients with TC-Hep had significantly increased median total bilirubin levels (7.5 mg/dL (IQR 6.8–8.9) vs 1.5 mg/dL (IQR 1.0–3.6), p < 0.0001), soluble interleukin-2 receptor levels (4512 IU/mL (IQR 4073–5771) vs 2997 IU/mL (IQR 1957–3237), p = 0.02), and percent of CD8+ T-cells expressing perforin (14.5 % (IQR 8.0–20.0) vs 1.0 % (IQR 0.8–1.0), p = 0.004) and granzyme (37.5 % (IQR 15.8–54.8) vs 4.0 % (IQR 2.5–5.5), p = 0.004) compared to IND-Hep patients. Clinical flow cytometry showed that TC-Hep patients had significantly increased percent CD8+ T cells (29.0 % (IQR 24.5–33.5) vs 23.6 % (IQR 19.8–25.8), p = 0.04) and HLA-DR+ (16.0 % (IQR 14.5–24.5) vs 2.7 (1.8–5.3), p < 0.001) compared to IND-Hep patients indicative of increase in CD8+ T cells that are activated.
Conclusions |
Peripheral blood clinical immune studies demonstrate increased markers of CD8 T-cell activation, proliferation, and cytotoxic function for TC-Hep patients. These readily available immune function labs can be used to help distinguish patients with TC-Hep from those with other causes. This provides a non-invasive tool for early detection of potential TC-Hep before progression to liver failure.
Il testo completo di questo articolo è disponibile in PDF.Graphical abstract |
Keywords : Pediatric acute liver failure, Immune dysregulation, Acute hepatitis, Aplastic anemia
Abbreviations : PALF, TC-Hep, IND-Hep, ALT, PT, INR, HE, IHC, EBV, IgM, TRIUMPH
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Vol 48 - N° 7
Articolo 102407- Agosto 2024 Ritorno al numero
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