HBV相关慢加急性肝衰竭患者外周血中Th1、Th2细胞及其细胞因子的变化和临床价值研究

Changes and clinical value of Th1,Th2 cells and cytokines in peripheral blood of patients with HBV associated acute-on-chronic liver failure

目的 探讨辅助性T细胞亚群1(Th1)、辅助性T细胞亚群2(Th2)细胞及其细胞因子水平在HBV相关慢加急性肝衰竭(HBV associated acute-on-chronic liver failure, HBV-ACLF)疾病进展中的相关变化。方法 选取2020年12月-2021年7月新疆医科大学第一附属医院感染中心确诊的45例HBV-ACLF患者为ACLF组,45例慢性乙型肝炎(Chronic hepatitis B,CHB)患者为CHB组,同期30例无任何肝病史的健康体检者为健康对照组(HC组)。采用流式细胞术检测Th1、Th2、Th1/Th2水平,采用酶联免疫吸附测定实验检测γ-干扰素(γ-interferon, IFN-γ)和白介素-4(Interleukin, IL-4)表达水平,分析HBV-ACLF患者肝功指标、终末期肝病模型(Model for end-stage liver disease, MELD)评分与Th1、Th2细胞及其细胞因子的相关性。采用受试者工作特征曲线(Receiver operator characteristic curve,ROC)分析上述指标对HBV-ACLF患者疾病严重程度的评判能力。结果 3组血浆丙氨酸氨基转移酶(Alanine aminotransferase, ALT)、天门冬氨酸氨基转移酶(Aspartate aminotransferase, AST)、总胆红素(Total-bilirubin, T-BIL)等肝功指标,Th1、Th2、Th1/Th2、IFN-γ和IL-4等表达水平均存在显著差异(P均<0.05)。相关性分析发现,Th2、Th1/Th2、IFN-γ与肝功指标和MELD评分显著相关(r>0.4或r<-0.4,P<0.05),且Th1/Th2水平与MELD评分呈强正相关(r>0.7)。ROC曲线发现,Th1、Th2、Th1/Th2及IFN-γ等指标对HBV-ACLF患者的疾病严重程度具有良好的预测能力。结论 在HBV-ACLF疾病进展中Th1、Th2、Th1/Th2、IFN-γ及IL-4表达水平存在显著改变,这对HBV-ACLF的疾病严重程度的预测具有较高的应用价值。

Objective To explore the changes of helper T cell 1(Th1),helper T cell 2(Th2)cells and the cytokine levels in the progression and prognosis of HBV associated acute-on-chronic liver failure(HBV-ACLF),and to provide the oretical data for clinical disease monitoring of HBV-ACLF.Methods In this study,45 HBV-ACLF patients diagnosed in the hospital from December 2020 to July 2021 were included in the ACLF group,and 45 chronic hepatitis B(CHB)patients were included in the CHB group and 30 cases of healthy people without any history of liver disease were included in the health control(HC)group.The levels of Th1,Th2 and Th1/Th2 were detected by flow cytometry and the expression level ofγ-interferon and interleukin-4 were detected by enzyme-linked immunosorbent assay.The correlation of liver function indexes and model for end-stage liver disease(MELD)scores with Th1 and Th2 cells and their cytokines in HBV-ACLF patients were analyzed.Finally,the receiver operator characteristic curve(ROC curve)was used to analyze the assessment ability of the above indicators on the disease severity of HBV-ACLF patients.Results There were significant differences in the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(T-BIL)etc liver function indexes,as well as Th1,Th2,Th1/Th2,IFN-γand IL-4(P<0.05).Correlation analysis found that Th2,Th1/Th2 and IFN-γwere significantly correlated with all liver function indexes and MELD scores(r>0.4 or r<-0.4,P<0.05),and Th1/Th2 levels had a strong positive correlation with MELD scores sex(r>0.7).After drawing the ROC curve,it was found that Th1,Th2,Th1/Th2 and IFN-γhad good predictive ability for the disease severity of HBV-ACLF patients.Conclusion The expression levels of Th1,Th2,Th1/Th2,IFN-γand IL-4 were significantly altered in HBV-ACLF,which has high application value for disease severity of HBV-ACLF.