血浆精氨酸酶1构建Logistic回归模型预测乙肝肝硬化失代偿风险的临床价值

Predicting decompensation of hepatitis B cirrhosis by ARG1 associated logistic regression model

目的探讨精氨酸酶-1(Arg-1)在乙肝肝硬化患者血浆表达的意义并评估其预测肝硬化失代偿风险的价值。方法收集2020年8月-2021年6月于中山大学附属第三医院就诊的乙肝肝硬化代偿期(HBV-CC)患者20例、行经颈静脉肝内门腔静脉分流术(TIPS)的乙肝肝硬化失代偿期(HBV-DC)患者20例,同时纳入同期健康体检者12人作为对照组。采用酶联免疫吸附试验测定外周血浆Arg-1浓度,另外检测乙肝肝硬化失代偿期患者门静脉血浆Arg-1浓度,并对血浆Arg-1浓度与肝硬化相关临床指标进行相关性分析和二元Logistic回归分析。结果乙肝肝硬化患者外周血浆Arg-1表达量明显高于对照组[(6.14±4.33)ng/mL vs.(3.24±1.30)ng/mL,t=3.713,P=0.001],HBV-DC组明显高于HBV-CC组和对照组[(7.54±5.32)ng/mL vs.(4.74±2.47)ng/mL、(3.24±1.30)ng/mL,P均<0.05],HBV-DC组外周血Arg-1表达量显著高于门静脉血[(7.54±5.32)ng/mL vs.(4.84±3.07)ng/mL,t=2.322,P=0.032]。乙肝肝硬化患者外周血浆Arg-1表达量与总胆汁酸、总胆红素、直接胆红素、APRI、FIB-4评分呈正相关。以发生肝硬化失代偿为因变量,纳入总胆红素、脾脏厚度、Arg-1等自变量进行多因素二元Logistic回归分析,结果显示:总胆红素升高(OR=15.42,95%CI:1.302~182.653,P=0.030)、脾脏厚度增大(OR=75.872,95%CI:4.657~1236.099,P=0.002)、Arg-1浓度超过4.45 ng/mL(OR=14.026,95%CI:1.234~159.403,P=0.033),均能显著增加肝硬化失代偿发生的风险。联合独立危险因素构建评分模型,并绘制列线图。HBV-DC发生概率的极佳临界值>34%,风险评分预测肝硬化患者发生失代偿的ROC曲线下面积为0.926(P<0.001),灵敏度为75%,特异度为95%。结论乙肝肝硬化患者血浆Arg-1表达量与肝脏生化功能、胆汁酸代谢、肝硬化分级以及失代偿风险相关,由总胆红素、脾脏厚度、Arg-1构建Logistic回归模型,对肝硬化失代偿发生有较高的预测价值。

Objective To investigate the significance of arginase-1(Arg-1)expression in plasma of patients with hepatitis B cirrhosis and evaluate its value in predicting the risk of cirrhosis decompensation.Methods 20 patients with HBV-relatedcompensated-cirrhosis(HBV-CC),20 patients with HBV-related-decompensated-cirrhosis(HBV-DC)that underwent transjugular intrahepatic portosystemic shunt(TIPS)in the Third Affiliated Hospital of Sun Yat-sen University from August2020 to June 2021 were collected.12 healthy subjects were included as health control(HC)group.Peripheral plasma Arg-1levels of all subjects and portal plasma Arg-1 levels in HBV-DC patients were detected by ELISA.The correlation analysis and binary logistic regression analysis were conducted between plasma Arg-1 concentration and clinical indicators of liver cirrhosis.Results Plasma Arg-1 levels were significantly higher in patients with liver cirrhosis(LC)than that in healthy controls[LC:(6.14±4.33)ng/mL,HC:(3.24±1.30)ng/mL;t=3.713,P=0.001].Plasma Arg-1 levels were significantly higher in HBV-DC patients than that in HBV-CC patients and healthy controls[DC:(7.54±5.32)ng/mL,CC:(4.74±2.47)ng/mL,HC:(3.24±1.30)ng/mL;P=0.006].Arg-1 levels in the peripheral plasma of the HBV-DC group were significantly higher than those in the portal blood[(7.54±5.32)ng/mL vs.(4.84±3.07)ng/mL;t=2.322,P=0.032].Plasma Arg-1 levels were positively correlated with total bile acid,total bilirubin,APRI and FIB-4 scores.The occurrence of decompensation of cirrhosis was taken as the dependent variable,and independent variables such as total bilirubin,spleen thickness and Arg-1 were included for multivariate logistic regression.The results showed total bilirubin increased(OR=15.42,95%CI 1.302-182.653,P=0.030),spleen thickness increased(OR=75.872,95%CI:4.657-1236.099,P=0.002)and Arg-1 concentration above 4.45 ng/mL(OR=14.026,95%CI:1.234-159.403,P=0.033)significantly increased the risk of decompensation of cirrhosis.Combined with independent risk factors,the scoring model was established.The terrific cut-off value for the probability of HBV-DC was>34%,and the area under ROC curve(AUC)was 0.926(P<0.001),with 75%sensitivity and95%specificity.Conclusions Plasma Arg-1 levels in patients with hepatitis B cirrhosis were correlated with liver biochemical function,bile acid metabolism,cirrhosis grade and progression to HBV-DC.The logistic regression model constructed from total bilirubin,spleen thickness and Arg-1 had high predictive value for the occurrence of decompensation of cirrhosis.