外周血HIF-1α和Cor在HBV感染相关慢加急性肝衰竭疾病进展及预后评估中的应用研究

Application of peripheral blood HIF-1αand Cor in progression and prognosis assessment of HBV infection-related acute-on-chronic liver failure

目的探讨外周血缺氧诱导因子1α(HIF-1α)、皮质醇(Cor)检测在乙型肝炎病毒(HBV)感染相关慢加急性肝衰竭(HBV-ACLF)疾病进展及预后评估中的价值。方法选取2020年4月-2021年9月在新乡医学院第一附属医院收治的80例HBV-ACLF患者,根据凝血酶原活动度(PTA)水平将其分为早期组(n=25)、中期组(n=29)和晚期组(n=26)。检测3组炎症细胞指标[白细胞计数(WBC)、中性粒细胞(NEUT)]、肝功能[丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBiL)和血肌酐(Cr)]、HBV-DNA水平、凝血功能[活化部分凝血活酶时间(APTT)、PTA、国际标准化比值(INR)]、Cor、HIF-1α水平,计算终末期肝病评分模型(MELD)评分,相关性分析HIF-1α、Cor水平与HBV-ACLF进展的关系。以患者预后情况将其分为死亡组(n=25)与存活组(n=55),比较2组HIF-1α、Cor水平;受试者工作特征(ROC)曲线分析HIF-1α、Cor检测对HBV-ACLF不良预后的评估价值。结果晚期组ALT、AST、TBiL、Cr、APTT、INR、WBC、NEUT、MELD评分、HIF-1α水平高于中期组和早期组,PTA、Cor水平低于中期组和早期组,差异均有统计学意义(P均<0.05);且中期组ALT、AST、TBiL、Cr、APTT、INR、WBC、NEUT、MELD评分、HIF-1α水平高于早期组,PTA、Cor水平低于早期组,差异均有统计学意义(P均<0.05)。Spearman相关性分析显示,HIF-1α水平与HBV-ACLF进展成正相关(r=0.501)、Cor水平与HBV-ACLF进展成负相关(r=-0.674),差异均有统计学意义(P均<0.05)。死亡组入院HIF-1α水平[(1587.33±400.65)pg/mL]高于存活组[(1022.79±417.96)pg/mL],Cor水平[(9.25±3.08)nmol/L]低于存活组[(14.01±3.99)nmol/L],差异均有统计学意义(P均<0.05)。ROC曲线分析显示,HIF-1α、Cor联合检测预测HBV-ACLF不良结局的曲线下面积(AUC)为0.875,高于HIF-1α、Cor单独检测的0.820、0.796。结论HBV-ACLF患者外周血HIF-1α与疾病进展成正相关,Cor与疾病进展成负相关,临床可以通过二者联合检测预测患者不良预后。

Objective To explore the value of peripheral blood hypoxia-inducible factor 1α(HIF-1α)and cortisol(Cor)in progression and prognosis assessment of hepatitis B virus(HBV)infection-related acute-on-chronic liver failure(HBV-ACLF).Methods A total of 80 patients with HBV-ACLF admitted to the First Affiliated Hospital of Xinxiang Medical College were enrolled between April 2020 and September 2021.According to the prothrombin activity(PTA),they were divided into early stage group(n=25),middle stage group(n=29)and late stage group(n=26).After diagnosis,inflammatory indexes[white blood cell count(WBC),neutrophil(NEUT)],liver function indexes[alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBiL),serum creatinine(Cr)],HBV-DNA,coagulation function indexes[activated partial thromboplastin time(APTT),PTA,international normalized ratio(INR)],Cor and HIF-1α were detected,and score of model for end-stage liver disease(MELD)was calculated.The relationship between HIF-1α,Cor and HBV-ACLF progression was analyzed.The patients were divided into death group(n=25)and survival group(n=55)according to their prognosis,the levels of HIF-1αand Cor were compared between the two groups.The evaluation value of HIF-1α and Cor for poor prognosis of HBV-ACLF was detected by receiver operating characteristic(ROC)curves.Results The levels of ALT,AST,TBiL,Cr,APTT,INR,WBC,NEUT,MELD and HIF-1α in late stage group were higher than those in middle stage group and early stage group,while the levels of PTA and Cor in late stage group were lower than those in middle stage group and early stage group;the differences were statistically significant(all P<0.05);and the levels of ALT,AST,TBiL,Cr,APTT,INR,WBC,NEUT,MELD and HIF-1αin the middle stage group were higher than those in the early stage group,while the levels of PTA and Cor in the middle stage group were lower than those in the early stage group;the differences were statistically significant(all P<0.05).Spearman correlation analysis showed that HIF-1α level was positively correlated with HBV-ACLF progression(r=0.501),and Cor level was negatively correlated with HBV-ACLF progression(r=-0.674);the differences were statistically significant(all P<0.05).At admission,HIF-1α level in death group[(1587.33±400.65)pg/mL]was higher than that in survival group[(1022.79±417.96)pg/mL],while Cor[(9.25±3.08)nmol/L]was lower than that in survival group[(14.01±3.99)nmol/L];the differences were statistically significant(all P<0.05).ROC curves analysis showed that the area under curve(AUC)of combined detection of HIF-1α and Cor was 0.875,which was higher than that of HIF-1αand Cor alone(0.820,0.796).Conclusions Peripheral blood HIF-1α was positively correlated with disease progression,while Cor was negatively correlated with it in HBV-ACLF patients.Clinically,combined detection could predict poor prognosis of patients.