血清IL-12、IL-18、CRP联合检测对肝硬化并发自发性细菌性腹膜炎患者预后的评估价值

Prognostic assessment value of combined serum IL-12,IL-18 and CRP detection in liver cirrhosis patients complicated with spontaneous bacterial peritonitis

目的探讨血清白细胞介素12(interleukin 12,IL-12)、白细胞介素18(interleukin 18,IL-18)、C反应蛋白(C-reactive protein,CRP)联合检测对肝硬化并发自发性细菌性腹膜炎(spontaneous bacterial peritonitis,SBP)患者的预后评估价值。方法选择2021年8月至2022年8月在承德医学院附属医院确诊并接受治疗的120例肝硬化并发SBP患者为研究对象,均给予相应的对症治疗,分别于入院当天和治疗14 d后采集患者空腹肘静脉血5 ml,采用酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测血清IL-12、IL-18水平,采用速率散射免疫比浊法检测血清CRP水平,分析治疗前后患者血清IL-12、IL-18、CRP水平变化情况。治疗结束后随访90 d,根据预后将患者分为存活组和死亡组,比较两组患者各项临床资料并采用Cox回归分析影响肝硬化并发SBP患者90 d内死亡的危险因素,绘制受试者工作特征(receiver operating characteristic,ROC)曲线评估血清IL-12、IL-18、CRP联合检测对肝硬化并发SBP患者预后的预测价值。结果120例患者均完成治疗,随访期间死亡21例,存活99例。治疗后患者血清IL-12[(36.67±4.57)ng/L比(67.53±8.16)ng/L]、IL-18[(60.19±7.04)ng/L比(111.06±12.58)ng/L]、CRP[(19.56±2.24)mg/L比(42.65±5.53)mg/L]水平均较治疗前显著降低(P均<0.05)。死亡组患者肝性脑病[33.33%(7/21)比14.14%(14/99)]、肝肾综合征[42.86%(9/21)比18.18%(18/99)]比例以及白蛋白[(22.34±2.52)g/L比(25.53±2.64)g/L]、总胆红素[(47.56±4.90)μmol/L比(33.34±3.58)μmol/L]、治疗后IL-12[(40.01±4.16)ng/L比(35.96±4.02)ng/L]、治疗后IL-18[(65.28±7.02)ng/L比(59.11±6.31)ng/L]、治疗后CRP[(23.19±3.34)mg/L比(18.79±2.36)mg/L]水平均高于存活组(P均<0.05)。Cox回归分析显示,肝性脑病(HR=1.893,95%CI:1.379~2.406,P<0.001)、肝肾综合征(HR=1.749,95%CI:1.225~2.273,P<0.001)、低白蛋白(HR=1.756,95%CI:1.108~2.404,P<0.001)、治疗后IL-12(HR=1.996,95%CI:1.226~2.765,P<0.001)、IL-18(HR=1.564,95%CI:1.117~2.010,P<0.001)、CRP(HR=2.385,95%CI:1.856~2.913,P<0.001)水平高均是导致肝硬化并发SBP患者90 d内死亡的危险因素。治疗后血清IL-12、IL-18、CRP水平联合预测肝硬化并发SBP患者90 d内死亡的ROC曲线下面积为0.906,约登指数为0.638,高于治疗后单独血清IL-12、IL-18、CRP预测的ROC曲线下面积(0.791、0.805、0.802;z值分别为2.996、2.819、2.847,P值分别为0.022、0.031、0.027)。结论血清IL-12、IL-18、CRP水平升高与肝硬化并发SBP患者90 d内死亡有关,可用于预测肝硬化并发SBP患者的死亡风险,三者联合的预测价值更高。

Objective To investigate the prognostic assessment value of combined serum interleukin 12(IL-12),interleukin 18(IL-18),and C-reactive protein(CRP)detection in liver cirrhosis patients complicated with spontaneous bacterial peritonitis(SBP).Methods Total of 120 liver cirrhosis patients complicated with SBP in Affiliated Hospital of Chengde Medical College from August 2021 to August 2022 were selected.The patients were given corresponding symptomatic treatment and 5 ml fasting elbow venous blood was collected on the day of admission and 14 d after treatment,serum IL-12 and IL-18 level was measured by enzyme-linked immunosorbent assay(ELISA)and serum CRP levels were measured by rate-scattering immunoturbidimetry,the changes of serum IL-12,IL-18 and CRP levels were analyzed before and after treatment.At the end of treatment,patients were followed up for 90 d and divided into survival group and death group according to their prognosis,clinical data was compared between the two groups and Cox regression analysis was used to analyze the risk factors affecting death within 90 d in liver cirrhosis patients complicated with SBP.The predictive value of serum IL-12,IL-18 and CRP on prognosis of liver cirrhosis patients complicated with SBP was assessed by receiver operating characteristic(ROC)curve.Results All of the 120 patients completed the treatment,21 cases died and 99 cases survived during the follow-up period.The serum IL-12[(36.67±4.57)ng/L vs.(67.53±8.16)ng/L],IL-18[(60.19±7.04)ng/L vs.(111.06±12.58)ng/L]and CRP[(19.56±2.24)mg/L vs.(42.65±5.53)mg/L]levels of patients after treatment were significantly lower than those before treatment(all P<0.05).The proportion of hepatic encephalopathy[33.33%(7/21)vs.14.14%(14/99)],proportion of hepatorenal syndrome[42.86%(9/21)vs.18.18%(18/99)],albumin[(22.34±2.52)g/L vs.(25.53±2.64)g/L],total bilirubin[(47.56±4.90)μmol/L vs.(33.34±3.58)μmol/L],IL-12 after treatment[(40.01±4.16)ng/L vs.(35.96±4.02)ng/L],IL-18 after treatment[(65.28±7.02)ng/L vs.(59.11±6.31)ng/L]and CRP after treatment[(23.19±3.34)mg/L vs.(18.79±2.36)mg/L]were significantly higher in death group than those in survival group(all P<0.05).Cox regression analysis showed that hepatic encephalopathy(HR=1.893,95%CI:1.379~2.406,P<0.001),hepatorenal syndrome(HR=1.749,95%CI:1.225~2.273,P<0.001),low albumin(HR=1.756,95%CI:1.108~2.404,P<0.001)and high IL-12(HR=1.996,95%CI:1.226~2.765,P<0.001),IL-18(HR=1.564,95%CI:1.117~2.010,P<0.001)and CRP(HR=2.385,95%CI:1.856~2.913,P<0.001)levels after treatment were risk factors for death within 90 d in liver cirrhosis patients complicated with SBP.The area under ROC curve of serum IL-12,IL-18 and CRP combined detection on death within 90 d in liver cirrhosis patients with SBP was 0.906(Youden index was 0.638),which was significantly higher than that of IL-12(0.791),IL-18(0.805)and CRP(0.802)alone(z=2.996,2.819,2.847;P=0.022,0.031,0.027).Conclusions Elevated serum IL-12,IL-18 and CRP levels are associated with death within 90 d in liver cirrhosis patients complicated with SBP and can be used to predict the risk of death in 90 d,and the predictive value of combination of IL-12,IL-18 and CRP was higher.