Identification of pediatric activated T-cell hepatitis using clinical immune studies
Catherine A Chapin1, Tamir Diamond2, Adriana Perez3
1Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA; Division of Gastroenterology, Hepatology and Nutrition, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
Insights
Pediatric acute liver failure (PALF) often results from activated T-cell hepatitis (TCHep). Clinical immune labs can identify TCHep, offering a non-invasive tool for early detection before liver failure progresses.
Area of Science:
- Pediatric Hepatology
- Immunology
- Clinical Diagnostics
Background:
- Pediatric acute liver failure (PALF) is frequently linked to immune dysregulation, specifically activated T-cell hepatitis (TCHep).
- Distinguishing TCHep from other causes of acute hepatitis in children is crucial for appropriate management.
Purpose of the Study:
- To characterize a cohort of children with acute severe hepatitis and PALF.
- To determine if clinical immune laboratory tests can help identify TCHep.
Main Methods:
- Retrospective review of 124 children with acute hepatitis and PALF (March 2020 - August 2022).
- Patients were categorized into known diagnoses, indeterminate hepatitis (IND-Hep), or TCHep groups.
- TCHep was defined by liver biopsy findings or development of aplastic anemia.
Main Results:
- TCHep patients (n=16) showed significantly higher total bilirubin, soluble interleukin-2 receptor levels, and CD8+ T-cell cytotoxic markers (perforin, granzyme) compared to IND-Hep patients (n=25).
- Clinical flow cytometry revealed increased CD8+ T cells and activated HLA-DR+ cells in TCHep patients.
- These immune markers indicate heightened CD8+ T-cell activation and cytotoxic function in TCHep.
Conclusions:
- Peripheral blood immune studies reveal elevated markers of CD8+ T-cell activation, proliferation, and cytotoxic function in TCHep.
- Readily available immune function tests can aid in differentiating TCHep from other causes of acute hepatitis.
- These non-invasive lab tests offer a tool for early TCHep detection, potentially preventing progression to liver failure.
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. Patients were classified as known diagnosis, indeterminate hepatitis (IND-Hep), or TCHep (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 TCHep, and 25 with IND-Hep. Patients with TCHep 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 TCHep 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 TCHep patients. These readily available immune function labs can be used to help distinguish patients with TCHep from those with other causes. This provides a non-invasive tool for early detection of potential TCHep before progression to liver failure.
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