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.
方法:2020年3月至2022年8月期间对急性肝炎和PALF儿童的回顾性回顾。患者被分类为已知诊断,不确定型肝炎(IND-Hep),或TC-Hep(通过肝活检确定为主要的CD8T细胞炎症或再生障碍性贫血的发展)。
结果:确定了124例患者:83例已知诊断,16与TC-Hep,和25IND-Hep。TC-Hep患者的中位总胆红素水平显着增加(7.5mg/dL(IQR6.8-8.9)vs1.5mg/dL(IQR1.0-3.6),p<0.0001),可溶性白细胞介素2受体水平(4512IU/mL(IQR4073-5771)与2997IU/mL(IQR1957-3237),p=0.02),和表达穿孔素的CD8+T细胞百分比(14.5%(IQR8.0-20.0)对1.0%(IQR0.8-1.0),p=0.004)和颗粒酶(37.5%(IQR15.8-54.8)vs4.0%(IQR2.5-5.5),p=0.004)与IND-Hep患者相比。临床流式细胞术显示,TC-Hep患者的CD8+T细胞百分比显着增加(29.0%(IQR24.5-33.5)vs23.6%(IQR19.8-25.8),p=0.04)和HLA-DR(16.0%(IQR14.5-24.5)比2.7(1.8-5.3),p<0.001)与IND-Hep患者相比,表明激活的CD8+T细胞增加。
结论:外周血临床免疫研究表明CD8T细胞活化的标志物增加,扩散,TC-Hep患者的细胞毒性功能。这些现成的免疫功能实验室可用于帮助区分TC-Hep患者与其他原因。这提供了用于在进展为肝衰竭之前早期检测潜在的TC-Hep的非侵入性工具。