血清IL-6和TNF-α对重症急性胰腺炎的早期诊断价值分析

Value of serum interleukin-6 and tumor necrosis factor-αin early diagnosis of severe acute pancreatitis

目的 评估血清细胞因子在重症急性胰腺炎(SAP)早期诊断中的价值,并利用LASSO算法构建复合指标的数理模型以提高对SAP诊断的准确性。方法 纳入2019年1月-2022年6月在常熟市第一人民医院就诊的130例急性胰腺炎患者,其中SAP患者73例,非SAP患者57例。收集所有患者的外周血清样本并通过Luminex xMAP液相芯片技术完成13种血清细胞因子的精准检测。同时,所有患者均进行APACHEⅡ、BISAP和CTSI评分。使用Kolmogorov-Smirnov法进行正态性检验,对符合正态分布的计量资料两组间比较采用成组t检验;对非正态分布的计量资料两组间比较采用Mann-Whitney U检验。计数资料两组间比较采用χ^(2)检验。此外,通过二元Logistic回归分析评估细胞因子对SAP的影响,应用线性回归分析评估细胞因子与SAP疾病的严重程度之间的关联。偏相关分析在校正协变量(年龄、性别、BMI、高血压、糖尿病病史)后分析细胞因子与SAP疾病的严重程度评分的关联性。利用LASSO算法构建复合指标的数理模型,并采用受试者工作特征曲线(ROC曲线)分析血清细胞因子对SAP临床诊断的效能,计算曲线下面积(AUC)。结果 非SAP组APACHEⅡ、BISAP和CTSI评分、改良Marshall评分均低于SAP组,差异均有统计学意义(P值均<0.001)。SAP组患者IFN-γ、IL-1β、IL-6、IL-8、TNF-α水平均高于非SAP组,IL-12水平明显低于非SAP组,差异均有统计学意义(P值均<0.05)。Logistic回归分析结果显示,IFN-γ(OR=1.190,95%CI:1.036~1.367,P=0.014)、IL-6(OR=1.148,95%CI:1.070~1.231,P<0.001)和TNF-α(OR=1.100,95%CI:1.048~1.155,P<0.001)为SAP的独立影响因素。偏相关分析提示,在校正了性别、年龄、BMI、慢性疾病史(糖尿病、高血压)后,SAP患者IL-6和TNF-α的水平与APACHEⅡ评分均呈显著正相关(IL-6:r=0.503,P<0.001;TNF-α:r=0.557,P<0.001)。线性回归分析显示,SAP患者中IL-6和TNF-α水平均与APACHEⅡ评分有关(IL-6:β=0.049,P=0.044;TNF-α:β=0.054,P=0.046),且IL-6和TNF-α存在交互作用,影响APACHEⅡ评分。ROC曲线分析显示,LASSO算法联合IL-6和TNF-α构建的风险评分区分SAP和非SAP的AUC值最大(AUC=0.925),而IL-6和TNF-α的AUC分别为0.885、0.878;偏相关分析发现,在校正性别、年龄、BMI、慢性疾病史(糖尿病、高血压)后,SAP患者风险评分与APACHEⅡ评分呈显著正相关(r=0.565,P<0.001)。结论 血清IL-6和TNF-α水平可反映AP疾病严重程度。联合血清IL-6和TNF-α构建的风险评分可显著提高SAP早期诊断的准确性,对SAP的临床诊疗具有重要的临床价值。

Objective To investigate the value of serum cytokines in the early diagnosis of severe acute pancreatitis(SAP),and to improve the accuracy of the diagnosis of SAP by establishing a mathematical model with composite indices based on LASSO algorithm.Methods A total of 130 patients with acute pancreatitis(AP)who attended Changshu First People’s Hospital from January 2019 to June 2022 were enrolled,among whom there were 73 SAP patients and 57 non-SAP patients.Peripheral serum samples were collected from all patients,and Luminex xMAP liquid chip technique was used to measure 13 serum cytokines.Meanwhile,Acute Physiology and Chronic Health EvaluationⅡ(APACHEⅡ),Bedside Index for Severity in Acute Pancreatitis(BISAP),and Computed Tomography Severity Index(CTSI)scores were determined for all patients.The Kolmogorov-Smirnov method was used for normality test;the independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups.Furthermore,the binary logistic regression analysis was used to evaluate the effect of cytokines on SAP,and the linear regression analysis was used to investigate the correlation between cytokines and SAP severity.The partial correlation analysis was used to evaluate the correlation between cytokines and SAP severity score after adjustment for covariates[age,sex,body mass index(BMI),and history of hypertension and diabetes].The LASSO algorithm was used to establish a mathematical model with composite indices;the receiver operating characteristic(ROC)curve was used to assess the performance of serum cytokines in the clinical diagnosis of SAP,and the area under the ROC curve(AUC)was calculated.Results Compared with the SAP group,the non-SAP group had significantly lower APACHEⅡ,BISAP,CTSI,and modified Marshall scores(all P<0.001).Compared with the non-SAP group,the SAP group had significantly higher levels of interferon-γ(IFN-γ),interleukin-6(IL-6),interleukin-8,and tumor necrosis factor-α(TNF-α)and a significantly lower level of interleukin-12(all P<0.05).The logistic regression analysis showed that IFN-γ(odds ratio[OR]=1.190,95%confidence interval[CI]:1.036-1.367,P=0.014),IL-6(OR=1.148,95%CI:1.070-1.231,P<0.001),and TNF-α(OR=1.100,95%CI:1.048-1.155,P<0.001)were independent influencing factors for SAP.The partial correlation analysis showed that after adjustment for sex,age,BMI,and history of chronic diseases(diabetes and hypertension),the levels of IL-6 and TNF-αwere positively correlated with APACHE II score in SAP patients(IL-6:r=0.503,P<0.001;TNF-α:r=0.557,P<0.001).The linear regression analysis showed that the levels of IL-6 and TNF-αwere associated with APACHE II score in SAP patients(IL-6:β=0.049,P=0.044;TNF-α:β=0.054,P=0.046),and there was an interaction between IL-6 and TNF-α,which affected APACHEⅡscore.The ROC curve analysis showed that the risk score based on IL-6 and TNF-αusing LASSO algorithm had the largest AUC of 0.925 in distinguishing SAP from non-SAP,while IL-6 or TNF-αalone had an AUC of 0.885 and 0.878,respectively.The partial correlation analysis showed that after adjustment for sex,age,BMI,and history of chronic diseases(diabetes and hypertension),the risk score was positively correlated with APACHEⅡscore in SAP patients(r=0.565,P<0.001).Conclusion The serum levels of IL-6 and TNF-αcan reflect the severity of AP.The risk score combining serum IL-6 and TNF-αcan significantly improve the accuracy of the early diagnosis of SAP,which has an important clinical value in the clinical diagnosis and treatment of SAP.