TLR4、MyD88、NF-κB在乙型肝炎病毒肝硬化患者中的表达及其临床意义

Expression of TLR4/MyD88/NF-κB signaling pathway in cirrhosis caused by hepatitisBvirus and its clinical significance

目的探讨Toll样受体4(TLR4)、髓样分化因子88(MyD88)、核转录因子-κ(NF-κB)信号通路在乙型肝炎病毒所致肝硬化中的表达及临床意义。方法选取2017年1月—2019年1月华北石油管理局总医院收治的130例乙型肝炎肝硬化患者为研究对照(肝硬化组),选择同期130例乙型肝炎患者为乙型肝炎组,选择130例健康人群为对照组。其中肝硬化组进一步根据ChildPugh分为A级(49例),B级(47例),C级(34例);根据肝硬化程度分为:代偿期肝硬化(49例),失代偿期肝硬化(48例),原发性肝癌(33例)。比较3组丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TBIL)的差异,比较3组单核细胞表面TLR4阳性率及血清MyD88、NF-κB水平,以及不同程度肝硬化患者TLR4、MyD88、NF-κB表达水平。采用Spearman或Pearson分析法分析TLR4、MyD88、NF-κB与ChildPugh分级、AST、ALT及TBIL的相关性,采用受试者工作特征(ROC)曲线分析ALT、AST、TBIL、TLR4、MyD88及NF-κB对肝硬化致原发性肝癌的诊断价值。结果肝硬化组、乙型肝炎组、对照组AST、ALT、TBIL水平比较,差异有统计学意义(P<0.05);TLR4、MyD88、NF-κB水平比较,差异有统计学意义(P<0.05);ChildPughA级、B级、C级患者TLR4、MyD88、NF-κB水平比较,差异有统计学意义(P<0.05);不同程度肝硬化患者TLR4、MyD88、NF-κB比较,差异有统计学意义(P<0.05)。TLR4、MyD88及NF-κB与ChildPugh分级、AST、ALT及TBIL均呈正相关(P<0.05)。ROC曲线结果显示,ALT截断值为101.44 u/L时,AUC为0.738;AST截断值为136.74 u/L时,AUC为0.706;TBIL截断值为51.86μmol/L时,AUC为0.746;TLR4截断值为32.342%时,AUC为0.896;MyD88截断值为931.402 pg/ml时,AUC为0.897;NF-κB截断值为1243.620 pg/ml时,AUC为0.875。结论TLR4、MyD88、NF-κB信号通路与乙型肝炎病毒所致肝炎及肝硬化病理进程密切相关,且TLR4、MyD88、NF-κB的检测在诊断肝硬化致原发性肝癌中具有一定临床价值。

Objective To investigate the clinical significance of TLR4/MyD88/NF-κB signaling pathway in cirrhosis induced by hepatitis B virus.Methods A total of 130 patients with hepatitis B cirrhosis admitted to our hospital from January 2017 to January 2019 were selected as the study control(cirrhosis group).130 patients with hepatitis B were selected as the hepatitis B group,and 130 healthy people were selected as the control group.The cirrhosis group was further divided into A grade(49 cases),B grade(47 cases),and C grade(34 cases).Classified according to the degree of cirrhosis:decompensated cirrhosis(n=49),decompensated cirrhosis(n=48),hepatocellular carcinoma(33 cases).Three groups of biochemical indicators(AST,ALT,TBIL),mononuclear cell surface TLR4 positive rate,and serum MyD88,NF-κB levels were compared.The positive rate of TLR4 on monocytes and the levels of serum MyD88 and NF-κB in patients with different degrees of cirrhosis were compared.The correlation between TLR4,MyD88,NF-κB,and ChildPugh classification,AST,ALT,TBIL was analyzed by spearman or Pearson analysis.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of ALT,AST,TBIL,TLR4,MyD88,and NF-κB in the conversion of cirrhosis to liver cancer.Results The levels of TLR4,MyD88,NF-κB,AST,ALT,and TBIL in the control group,hepatitis B group,and cirrhosis group gradually increased(P<0.05);Childpugh A,B,TLR4,MyD88,and NF-κB levels of patients with grade C increased significantly(P<0.05);TLR4,MyD88,and NF-κB of patients with compensated cirrhosis,decompensated cirrhosis,and primary liver cancer showed an upward trend(P<0.05).TLR4,MyD88,and NF-κB were positively related with ChildPugh classification,AST,ALT,and TBIL(P<0.05).ROC curve results showed that when the ALT cutoff value was 101.44 U/L,the AUC was 0.738;when the AST cutoff value was 136.74 U/L,the AUC was 0.706;when the TBIL cutoff value was 51.86μmol/L,the AUC was 0.746;When cutoff value of the TLR4 was 32.342%,the AUC was 0.896;when the cut-off value of MyD88 was 931.402 pg/ml,the AUC was 0.897;when the cut-off value of NF-κB was 1,243.620 pg/ml,the AUC was 0.875.Conclusion The TLR4/MyD88/NF-κB signaling pathway is closely related to the pathogenesis of hepatitis and cirrhosis caused by hepatitis B virus.It is positively correlated with the severity of liver cirrhosis and the degree of liver injury.TLR4,MyD88,and NF-κB have certain clinical value in the diagnosis of liver cirrhosis.