乙型肝炎肝硬化合并2型糖尿病患者血清热休克蛋白70、可溶性程序性死亡蛋白1和25-羟基维生素D_(3)水平与预后的相关性研究

The correlation between serum heat shock protein 70,soluble programmed death protein 1,25-hydroxy vitamin D_(3) levels and prognosis in patients with hepatitis B associated liver cirrhosis combined with type 2 diabetes mellitus

目的探讨乙型肝炎肝硬化(HBLC)合并2型糖尿病(T2DM)患者血清热休克蛋白70(HSP70)、可溶性程序性死亡蛋白1(sPD-1)、25-羟基维生素D_(3)[25(OH)VD_(3)]的表达及对预后的评估价值。方法回顾性分析2018年6月至2019年11月浙江普陀医院97例HBLC合并T2DM患者(HBLC合并T2DM组)、105例单纯HBLC患者(HBLC组)和118例单纯T2DM患者(T2DM组)的临床资料。比较三组血清HSP70、sPD-1和25(OH)VD_(3)水平,分析其与肝功能指标[丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)]、血糖[空腹血糖(FBG)和糖化血红蛋白(HbAlc)]的相关性。并根据HBLC合并T2DM患者治疗6个月后的预后分为预后不良(28例)和预后良好(69例),比较两者HSP70、sPD-1、25(OH)VD_(3)和肝功能Child-Pugh分级;采用受试者工作特征(ROC)曲线分析HSP70、sPD-1和25(OH)VD_(3)对HBLC合并T2DM患者预后的评估效能。结果HBLC合并T2DM组HSP70和sPD-1明显高于HBLC组和T2DM组[(4.28±1.19)μg/L比(2.27±0.76)和(2.40±0.84)μg/L、(7.86±2.45)ng/L比(4.23±1.62)和(3.85±1.27)ng/L],25(OH)VD_(3)明显低于HBLC组和T2DM组[(13.62±3.96)μg/L比(18.63±6.11)和(17.45±4.36)μg/L],差异有统计学意义(P<0.05);HBLC组与T2DM组比较差异无统计学意义(P>0.05)。Pearson相关分析结果显示,在HBLC合并T2DM患者中,HSP70和sPD-1与ALT、AST、FBG、HbAlc呈正相关(P<0.01),25(OH)VD_(3)与ALT、AST、FBG、HbAlc呈负相关(P<0.01)。在HBLC合并T2DM患者中,预后不良患者HSP70、sPD-1和Child-Pugh分级B级率明显高于预后良好者[(6.03±1.63)μg/L比(3.57±1.02)μg/L、(9.86±1.59)ng/L比(7.05±2.62)ng/L和71.43%(20/28)比30.43%(21/69)],25(OH)VD_(3)明显低于预后良好患者[(9.26±3.02)μg/L比(15.39±5.84)μg/L],差异有统计学意义(P<0.01或<0.05)。ROC曲线分析结果显示,HSP70、sPD-1和25(OH)VD_(3)联合预测HBLC合并T2DM预后的曲线下面积最大,为0.890,灵敏度和特异度分别为89.29%和79.71%。结论HBLC合并T2DM患者血清HSP70、sPD-1明显升高,25(OH)VD_(3)明显降低,并与肝功能、血糖存在良好线性关系,早期联合检测HSP70、sPD-1和25(OH)VD_(3)可为临床对症治疗、预后评估提供新思路。

Objective To investigate the expression of serum heat shock protein 70(HSP70),soluble programmed death protein 1(sPD-1),and 25-hydroxy vitamin D_(3) in hepatitis B associated liver cirrhosis(HBLC)combined with type 2 diabetes mellitus(T2DM)and their value in prognostic prediction.Methods The clinical data of 97 patients with HBLC combined with T2DM(HBLC combined with T2DM group),105 patients with HBLC(HBLC group)and 118 patients with T2DM(T2DM group)from June 2018 to November 2019 in Zhejiang Putuo Hospital were prospectively analyzed.The serum levels of HSP70,sPD-1 and 25-hydroxy vitamin D_(3) were compared among 3 groups,and the correlation between above serum indexes and liver function indexes,blood sugar indexes were analyzed.The liver function indexes included alanine aminotransferase(ALT)and aspartate aminotransferase(AST),and the blood sugar indexes included fasting blood glucose(FBG)and glycosylated hemoglobin(HbA1c).According to the prognosis 6 months later,the patients with HBLC combined with T2DM were divided into poor prognosis(28 cases)and good prognosis(69 cases),and the HSP70,sPD-1,25-hydroxy vitamin D_(3) and liver function Child-Pugh classification were compared.The predictive value of serum HSP70,sPD-1 and 25-hydroxy vitamin D_(3) on prognosis in patients with HBLC combined with T2DM was analyzed by receiver operating characteristic(ROC)curve.Results The HSP70 and sPD-1 in HBLC combined with T2DM group were significantly higher than those in HBLC group and T2DM group:(4.28±1.19)μg/L vs.(2.27±0.76)and(2.40±0.84)μg/L,(7.86±2.45)ng/L vs.(4.23±1.62)and(3.85±1.27)ng/L,the 25-hydroxy vitamin D_(3) was significantly lower than that in HBLC group and T2DM group:(13.62±3.96)μg/L vs.(18.63±6.11)and(17.45±4.36)μg/L,and there were statistical differences(P<0.05);there were no statistical differences between HBLC group and T2DM group(P>0.05).The Pearson correlation analysis result showeds that HSP70 and sPD-1 were positively correlated with ALT,AST,FBG and HbA1c(P<0.01),the 25-hydroxy vitamin D_(3) was negatively correlated with ALT,AST,FBG and HbA1c(P<0.01)in patients with HBLC combined with T2DM.In patients with HBLC combined with T2DM,the HSP70,sPD-1 and rate of Child-Pugh classification B in patients with poor prognosis were significantly higher than those in patients with good prognosis:(6.03±1.63)μg/L vs.(3.57±1.02)μg/L,(9.86±1.59)ng/L vs.(7.05±2.62)ng/L and 71.43%(20/28)vs.30.43%(21/69),the 25-hydroxy vitamin D_(3) was significantly lower than that in patients with good prognosis:(9.26±3.02)μg/L vs.(15.39±5.84)μg/L,and there were statistical differences(P<0.01 or<0.05).The ROC curve analysis result showed that the area under curve of HSP70,sPD-1 combined with 25-hydroxy vitamin D_(3) in predicting prognosis was the highest in patients with HBLC combined with T2DM,which was 0.890,with a sensitivity of 89.29%and a specificity of 79.71%.Conclusions The levels of serum HSP70 and sPD-1 in patients with HBLC combined with T2DM increase,and the level of 25-hydroxy vitamin D_(3) decreases.There is a good linear relationship with liver function and blood glucose.Early combined detection of the above serum levels can provide new ideas for clinical implementation of symptomatic treatment and prognosis prediction.