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 hepatitis B virus and its clinical significance

摘要:

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51.86 μmol/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1 243.620 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。

Abstract:

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.