RIPK3介导肝细胞程序性坏死在乙型肝炎相关慢加急性肝衰竭中的作用

The role of RIPK3-mediated necroptosis in patients with HBV-related acute-on-chronic liver failure

目的探讨受体相互作用蛋白激酶3(RIPK3)介导肝细胞程序性坏死在乙型肝炎相关慢加急性肝衰竭中的作用。方法共纳入140例受试者并采集血清,其中乙型肝炎相关慢加急性肝衰竭(HBV-ACLF)40例、乙型肝炎肝硬化(HBV-LC)40例、慢性乙型肝炎(CHB)40例以及健康对照(HC)20例。检测血清RIPK3水平的表达,并与ALT、AST水平进行相关性分析。结果总的肝病患者血清RIPK3水平(447.41±1089.425)pg/mL显著高于健康对照组[(0.62±2.78)pg/mL,P<0.0001],且随着疾病严重程度的增加,血清RIPK3水平呈递增趋势,其中以HBV-ACLF组(1195.31±1622.95)pg/mL最高。所有肝病患者血清中RIPK3水平与ALT(r=0.5804,P<0.0001)、AST(r=0.8114,P<0.0001)、总胆红素(r=0.5388,P<0.0001)、PT(r=0.5690,P<0.0001)和INR(r=0.5724,P<0.0001)呈显著正相关。结论 RIPK3介导的肝细胞程序性坏死在乙型肝炎相关慢加急性肝衰竭病情进展中发挥重要作用。

Objective To investigate the role of RIPK3-mediated necroptosis in patients with HBV-related acute-on-chronic liver failure.Methods Total 140 subjects were recruited,including 40 patients with HBV related acute-on-chronic liver failure(HBV-ACLF),40 patients with HBV-related liver cirrhosis(HBV-LC),40 chronic hepatitis B patients(CHB),and 20 heathy controls.Serum RIPK3 levels were measured,and the correlation between ALT/AST with serum RIPK3 levels were analyzed.Results Serum RIPK3 levels in all patients with liver diseases[30.94(0.00,459.10)pg/mL],including HBV-ACLF,HBV-LC and CHB,were significantly higher than that in healthy controls[0.00(0.00,0.00)pg/mL](P<0.0001).Moreover,serum RIPK3 levels gradually elevated as the severity of liver desease increased,especially in HBV-ACLF group[870.35(337.80,1426.97)pg/mL].Significant positive correlation was found between serum RIPK3 and ALT levels(r=0.5804,P<0.0001),AST levels(r=0.8114,P<0.0001),TBIL(r=0.5388,P<0.0001),PT(r=0.5690,P<0.0001),as well as INR(r=0.5724,P<0.0001)in patients with liver disease.Conclusion Necroptosis,mediated by RIPK3,plays a significant role in HBV-ACLF.