乙型肝炎肝硬化患者血清GRP78、caspase-12表达与肝脏炎症的相关性分析

Correlations of glucose regulated protein 78 and caspase-12 expressions in peripheral blood with liver inflammation in patients with hepatitis B cirrhosis

目的观察乙型肝炎肝硬化患者血清葡萄糖调节蛋白78(glucose regulated protein 78, GRP78)、caspase-12水平,探讨其表达与患者肝脏炎症的关系。方法 83例乙型肝炎肝硬化患者均行常规综合治疗48周,根据治疗后患者肝脏炎症活动度分为进展组17例和未进展组66例;采用ELISA法检测血清GRP78、caspase-12水平,比较治疗前、后患者血清GRP78、caspase-12水平;采集患者基线资料,并进行2组间比较;采用多因素logistic回归分析乙型肝炎肝硬化患者肝脏炎症活动度进展的影响因素;采用双变量Pearson直线相关性分析乙型肝炎肝硬化患者血清GRR78水平与caspase-12的相关性;绘制ROC曲线,评估血清caspase-12、GRP78水平对预测乙型肝炎肝硬化患者肝脏炎症活动度进展的效能。结果治疗48周时,83例患者血清GRP78、caspase-12水平均低于治疗前(P<0.05),其中17例患者肝脏炎症进展,占20.48%;进展组患者血清GRP78[(45.69±5.17)μg/L]、caspase-12[(57.05±5.41)u/L]水平均高于未进展组[(39.63±5.10)μg/L、(48.52±5.36)u/L](P<0.05);GRP78、caspase-12是乙型肝炎肝硬化患者肝脏炎症活动度进展的影响因素(OR=1.43,95%CI:1.15~1.78,P<0.001;OR=1.44,95%CI:1.14~1.82,P<0.001)。乙型肝炎肝硬化患者血清GRP78水平与caspase-12呈正相关(r=0.39,P<0.001)。血清GRP78、caspase-12水平的最佳截断值分别为41.23μg/L、50.52 u/L时,GRP78、caspase-12单独及联合预测乙型肝炎肝硬化患者肝脏炎症活动度进展的AUC分别为0.92(95%CI:0.86~0.99,P<0.001)、0.87(95%CI:0.88~0.99,P<0.001)、0.94(95%CI:0.80~0.95,P<0.001),灵敏度分别为96.0%、96.0%、97.0%,特异度分别为43.0%、67.0%、36.0%。结论乙型肝炎肝硬化患者外周血GRP78、caspase-12过表达提示患者肝脏炎症程度重或有持续进展风险,动态监测患者血清GRP78、caspase-12水平对指导临床早期预测和干预肝脏炎症进展有一定意义。

Objective To observe the levels of glucose regulated protein 78(GRP78) and caspase-12 in peripheral blood in patients with hepatitis B cirrhosis, and to investigate the relationships of their expressions with liver inflammation. Methods Eighty-three patients with hepatitis B cirrhosis received conventional comprehensive therapy for 48 weeks, and were divided into progressive group(n=17) and non-progressive group(n=66) according to the liver inflammatory activity after treatment. The levels of GRP78 and caspase-12 in peripheral blood were detected by ELISA, and were compared before and after treatment. The baseline data were collected and compared between two groups. Multivariate logistic regression analysis was used to assess the influencing factors of liver inflammatory activity progression in patients with hepatitis B cirrhosis. Bivariate Pearson linear correlation analysis was used to assess the correlation of GRP78 with caspase-12 in patiants with hepatitis B circhosis.ROC was drawn to analyze the values of caspase-12 and GRP78 expressions to the prediction of the disease progression of patients with hepatitis B cirrhosis. Results In 48 weeks of treatment, the levels of GRP78 and caspase-12 of 83 patients were lower than those before treatment(P<0.05), and among them, 17 patients had progressive liver inflammation, accounting for 20.48%. The levels of GRP78 and caspase-12 were higher in progressive group((45.69±5.17) μg/L,(57.05±5.41) u/L) than those in non-progressire group((39.63±5.10) μg/L,(48.52±5.36) u/L)(P<0.05). GRP78 and caspase-12 were the influencing factors of liver inflammatory activity progression in patients with hepatitis B cirrhosis(OR=1.43, 95%CI:1.15-1.78, P<0.001;OR=1.44,95%CI:1.14-1.82,P<0.001).The serum GRP78 level was positively correlated with caspase-12(r=0.39,P<0.001)in patients with hepatitis B cirrhosis.When the optimal cut-off values of GRP78 and caspase-12 were 41.23μg/L and 50.52 u/L,the AUCs of GRP78,caspase-12 and GRP78+caspase-12 for predicting the disease progression were 0.92(95%CI:0.86-0.99,P<0.001),0.87(95%CI:0.88-0.99,P<0.001),and 0.94(95%CI:0.80-0.95,P<0.001),the sensitivities were 96%,96% and 97%,and the specificities were 43%,67% and 36%,respectively.Conclusion The overexpressions of GRP78 and caspase-12 in peripheral blood may indicate the progression of liver inflammation or the risk of continuous progression in patients with hepatitis B cirrhosis,and dynamic monitoring of GRP78 and caspase-12 levels is of significance in guiding early prediction and intervention of liver inflammatory progression.