Chapin Catherine A, Diamond Tamir, Perez Adriana, Kreiger Portia A, Loomes Kathleen M, Behrens Edward M, Alonso Estella M
Department 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.
Department of Pediatrics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA; Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Clin Res Hepatol Gastroenterol. 2024 Aug;48(7):102407. doi: 10.1016/j.clinre.2024.102407. Epub 2024 Jun 25.
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.
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).
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.
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.
大多数不明原因的儿童急性肝衰竭（PALF）病例继发于免疫失调，称为活化T细胞肝炎（TCHep）。我们旨在描述一组患有急性重型肝炎和PALF的儿童，并确定临床免疫实验室检查如何有助于识别TCHep组。
回顾性分析2020年3月至2022年8月期间患有急性肝炎和PALF的儿童。患者被分类为已知诊断、不明原因肝炎（IND-Hep）或TCHep（通过肝活检以CD8 T细胞炎症为主或发生再生障碍性贫血来定义）。
共识别出124例患者：83例为已知诊断，16例为TCHep，25例为IND-Hep。与IND-Hep患者相比，TCHep患者的总胆红素中位数显著升高（7.5mg/dL（四分位间距6.8 - 8.9）对1.5mg/dL（四分位间距1.0 - 3.6），p < 0.0001）、可溶性白细胞介素-2受体水平升高（4512IU/mL（四分位间距4073 - 5771）对2997IU/mL（四分位间距1957 - 3237），p = 0.02），以及表达穿孔素的CD8 + T细胞百分比升高（14.5%（四分位间距8.0 - 20.0）对1.0%（四分位间距0.8 - 1.0），p = 0.004）和颗粒酶升高（37.5%（四分位间距15.8 - 54.8）对4.0%（四分位间距2.5 - 5.5），p = 0.004）。临床流式细胞术显示，与IND-Hep患者相比，TCHep患者的CD8 + T细胞百分比显著升高（29.0%（四分位间距24.5 - 33.5）对23.6%（四分位间距19.8 - 25.8），p = 0.04）以及HLA-DR +升高（16.0%（四分位间距14.5 - 24.5）对2.7（1.8 - 5.3），p < 0.001），表明活化的CD8 + T细胞增加。
外周血临床免疫研究表明，TCHep患者的CD8 T细胞活化、增殖和细胞毒性功能标志物增加。这些易于获得的免疫功能实验室检查可用于帮助区分TCHep患者与其他病因患者。这为在进展至肝衰竭之前早期检测潜在的TCHep提供了一种非侵入性工具。
