Department of Liver Intensive Care Unit (WY, XM, YYZ, ZGZ, YZ, HZ, YL, JFW, ZPQ), Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
Department of Liver Intensive Care Unit (WY, XM, YYZ, ZGZ, YZ, HZ, YL, JFW, ZPQ), Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
Am J Med Sci. 2020 Dec;360(6):656-661. doi: 10.1016/j.amjms.2020.06.023. Epub 2020 Jun 28.
Interleukin-33 (IL-33), along with its receptor suppression of tumorigenicity 2 (ST2), is capable of regulating immune responses. Immunologically mediated events play a critical role in the acute phase of chronic hepatitis B (CHB) infection. The present study primarily aimed to determine whether the IL-33/ST2 axis could be used as a reliable biomarker to predict disease progression and prognosis.
The study included 130 cases of CHB, with 48 cases in stable condition, 50 cases of progression to hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF), and 32 cases of progression to HBV related pre-ACLF. The demographic data and laboratory test results were recorded and compared among the groups. The blood samples for the measurement of serum IL-33 and soluble ST2 (sST2) levels were collected at admission and evaluated twice using the ELISA method.
The patients in which the disease progressed to HBV-ACLF had the highest serum IL-33 and sST2 levels among the three groups (p<0.001). The correlation analysis showed that the serum IL-33 levels were associated with the levels of ALT (r = 0.367, p<0.001), AST (r = 0.456, p<0.001) and the MELD score (r = 0.377, p = 0.001). The area under the curve (AUC) of IL-33 and sST2 levels for differentiation of disease progression were 0.861 (95% CI: 0.787-0.934, p<0.001) and 0.788 (95% CI: 0.692-0.884, p<0.001), respectively. The serum IL-33 levels combined with the MELD score had the highest 90-day mortality prediction efficiency, with an AUC of 0.918 (95% CI: 0.859-0.977, p<0.001), a sensitivity of 92.3%, and a specificity of 88.7%.
The IL-33/sST2 axis could be used to evaluate the progression and mortality in CHB patients with hepatic flare. The combinatorial use of multiple indicators could achieve the highest diagnostic and predictive accuracy.
白细胞介素-33（IL-33）及其受体抑制肿瘤发生 2（ST2）能够调节免疫反应。免疫介导的事件在慢性乙型肝炎（CHB）感染的急性期中起着关键作用。本研究主要旨在确定 IL-33/ST2 轴是否可用作预测疾病进展和预后的可靠生物标志物。
该研究纳入了 130 例 CHB 患者，其中 48 例病情稳定，50 例进展为乙型肝炎病毒（HBV）相关慢加急性肝衰竭（ACLF），32 例进展为 HBV 相关 ACLF 前期。记录并比较了各组的人口统计学数据和实验室检查结果。入院时采集血样测量血清 IL-33 和可溶性 ST2（sST2）水平，并使用 ELISA 法进行两次评估。
疾病进展为 HBV-ACLF 的患者三组中血清 IL-33 和 sST2 水平最高（p<0.001）。相关性分析显示，血清 IL-33 水平与 ALT（r=0.367，p<0.001）、AST（r=0.456，p<0.001）和 MELD 评分（r=0.377，p=0.001）相关。IL-33 和 sST2 水平区分疾病进展的曲线下面积（AUC）分别为 0.861（95%CI：0.787-0.934，p<0.001）和 0.788（95%CI：0.692-0.884，p<0.001）。血清 IL-33 水平联合 MELD 评分对 90 天死亡率的预测效率最高，AUC 为 0.918（95%CI：0.859-0.977，p<0.001），灵敏度为 92.3%，特异性为 88.7%。
IL-33/sST2 轴可用于评估乙型肝炎患者肝内炎症活动的进展和死亡率。联合使用多个指标可以达到最高的诊断和预测准确性。
