Clinical Rearch On The Diagnostic Value Of Lipocalin2 In Patients With Acute Cholangitis

Objective:The aim of this study was to evaluate the diagnostic value of serum lipocalin2(LCN2)in patients with acute cholangitis(AC)and acute cholangitis patients with sepsis,attempting to provide a novel biomarker with more accurate and effective diagnostic power for the patients with AC.Methods:1.Patients who were confirmed to havr an AC diagnosis and treated in the Department of Hepatobiliary Surgery at the First Affiliated Hospital of Chongqing Medical University from November 2020 to December 2021 were enrolled.According to the Tokyo Guidelines 2018 for the severity assessment of acute cholangitis,we divided the enrolled patients into mild,moderate and severe groups(Grade Ⅰ,Grade Ⅱ and Grade Ⅲ).Based on the diagnostic criteria of sepsis,all AC patients were divided into sepsis group and general AC group and we added healthy control group.Patients with sepsis were divided into general sepsis group and septic shock group.According to the 30-day survival status,we divided AC patients with sepsis into survival group and death group.2.We collected clinical data including white blood cell(WBC)count,C-reaction protein(CRP),procalcitonin(PCT)and neutrophil-lymphocyte ratio(NLR)and so on.Blood samples were obtained on admission and at24 h,72h after biliary-drainage,and ELISA(enzyme-linked immunosorbent assay)was used for measuring the LCN2 level.We compared the differences of LCN2 level and other clinical indices between groups.Collinearity between LCN2 and other inflammantory markers were evaluated by Spearman’s correlation coefficient,and the relationships between inflammantory markers and three clinical assessment methods as well as the ICU stay were evaluated by the same method.3.Throngh the receiver operating characteristic(ROC)analysis and Delong test,we compared the abilities of LCN2 levels on admission to predict for judging different severity of AC patients with the abilities of other inflammantory markers levels.4.We compared the changes of clinical indices on admission and at 24 hours and 72 hours after biliary-drainage.5.Risk factors for 30 days mortality in AC patients with sepsis were identified by using univariate and multivariate analysis,and the predictive value of the five inflammantory markers and three clinical assessment methods in AC patients with sepsis were evaluated by the ROC and area under curve of ROC(AUC).A two-sided P value less than 0.05 was considered statistically significant.Results:1.In total,108 patients with AC were enrolled in this study,including43 Grade Ⅰ,29 Grade Ⅱ and 36 Grade Ⅲ cases.Of 53 patients with sepsis,15 patients suffered septic shock.Finally,8 patients died within 30 days.2.There were significant differences between severity grading groups on these inflammantory markers LCN2,PCT,CRP,NLR and WBC,and LCN2 had strong positive correlations with PCT、CRP、NLR and WBC(r=0.8053,r=0.6299,r=0.5457,r=0.4096,P<0.001).3.The AUC of LCN2 in predicting moderate and severe AC(vs.mild AC)was 0.925,prominently higher than that of other inflammantory markers,and the optimal cutoff value of LCN2 was 262.2ng/mL(sensitivity,90.8%;specificity,81.4%).The AUC of LCN2 combined with NLR(0.940)was larger than that of LCN2 combined with other inflammantory markers,and the sensitivity and specificity of the optimal cutoff value were 89.2% and 88.4%,respectively.4.The AUC of LCN2 in predicting severe AC(vs.mild and moderate AC)was 0.912,prominently higher than that of other inflammantory markers,and the optimal cutoff value of LCN2 was 325.7ng/mL(sensitivity,86.1%;specificity,83.3%).The AUC of LCN2 combined with NLR(0.916)was larger than that of LCN2 combined with other inflammantory markers,and the sensitivity and specificity of the optimal cut-off value were 91.7% and 80.6%,respectively.5.After biliary drainage,the level of LCN2 decreased gradually,from292.7ng/mL(236.4-368.6)in pre-operation group to 230.9ng/mL(183.1-291.7)in postoperative 24 h,173.8ng/mL(139.3-206.6)in postoperative 72 h group.The differences between groups were statistical significance(P<0.05).6.The level of serumLCN2 in AC group(245.3 ng/mL(205.3-283.2))was higher than that in healthy control group(136.0 ng/mL(105.8-151.0))and lower than that in sepsis group(362.2ng/mL(325.9-413.6)),with statistically significant differences(P<0.05).The AUC of LCN2 in predicting the AC patients with sepsis(AC vs.sepsis)was 0.903,prominently higher than that of other inflammantory markers,and the optimal cutoff value of LCN2 was 307.4ng/mL,with sensitivity of 81.1%and specificity of 89.1%.The AUC of LCN2 in predicting septic shock(moderate sepsis vs.sepsis shock)was 0.905,prominently higher than that of other inflammantory markers,and the optimal cutoff value of LCN2 was388.5ng/mL,with sensitivity of 86.7% and specificity of 86.9%.7.LCN2 had moderate positive correlations with APACHE Ⅱ,SOFA,NEWS scores and ICU-stays(r=0.727,r=0.652,r=0.706,r=0.424,P<0.05),by Spearman test.The LCN2 concentration,APACHE Ⅱ and NEWS scores in death group were significantly higher than those in survival group by univariate analysis(P<0.05).Multivariate logistic regression analysis showed that APACHE Ⅱ score and LCN2 concentration were the independent risk factors for 30-day mortality in the AC patients with sepsis.The AUC of LCN2 in predicting 30-day mortality for the AC patients with sepsis was 0.828,which was higher than that of other indices and followed by APACHE Ⅱ.Through Youden index analysis,the optimal cut-off value of LCN2 for predicting 30-day mortality in the AC patients with sepsis was397.2ng/mL,with a sensitivity of 87.5% and specificity of 82.2%.Conclusion:1.The serumLCN2 on patient admission showed higher accuracy of predicting moderate/severe AC and severe AC;2.SerumLCN2 showed better dignostic value in predicting AC patients with sepsis or septic shock;3.LCN2 and APACHE Ⅱ scores could be used as independent risk factors for predicting 30-day mortality in the AC patients with sepsis;4.Dynamic monitoring the changes in serumLCN2 level might be helpful in understanding the changes of AC patients’ condition;5.Compared with traditional inflammatory markers such as WBC,CRP,PCT and NLR,LCN2 performed better in early diagnosis,risk stratification and survival prognosis of AC patients with or without sepsis.