【作者】 余静；

【导师】 白爱平；

【作者基本信息】 南昌大学 ， 内科学（消化内科）（专业学位）， 2021， 硕士

【摘要】 背景:炎症性肠病(inflammatory bowel disease,IBD)主要包括克罗恩病(Crohn’s disease,CD)和溃疡性结肠炎(ulcerative colitis,UC),是一种涉及胃肠道的慢性疾病。近年来,IBD的发病率在我国逐步增加,己经逐渐成为消化系统的常见病。当前IBD临床治疗效果欠佳并且该疾病易反复发作,患者需长期随访以监测活动度并且及时调整治疗方案。一直以来,内镜检查及病理活检是评估IBD病情活动度的金标准,但内镜检查费用昂贵、具有侵入性,有相关的出血、穿孔并发症和死亡率的风险,病患依从性较差等缺点;因此,寻找简便、无创的评估指标成为当前研究热点。先前的研究表明中性粒细胞-淋巴细胞比率(Neutrophil to lymphocyte ratio,NLR)、单核细胞与淋巴细胞比值(Monocyte to lymphocyte ratio,MLR)、血小板与淋巴细胞比值(Platelet to lymphocyte ratio,PLR)与克罗恩病或者溃疡性结肠炎疾病的活动性密切相关,但结论不一,本文主要研究NLR、MLR、PLR在不同疾病活动度的IBD患者中是否存在差异,NLR、MLR、PLR是否对IBD病情活动度的评估具有价值。目的:通过分析NLR、MLR、PLR等指标在IBD患者及健康人群间的差异,并比较IBD患者不同疾病活动度(轻中重)组中NLR、MLR、PLR等指标的差异,探索NLR、MLR、PLR与IBD疾病活动度的关系,分析NLR、MLR、PLR是否可作为评估IBD病情活动度的指标。方法:选取2016年1月至2020年12月在我院消化内科初次诊断为IBD的患者作为病例组,并分为UC组(146例)和CD组(47例);根据改良Mayo评分UC组分为轻度组(10例)、中度组(13例)及重度组(23例);根据best CDAI评分CD组分为轻度组(51例)、中度组(81例)及重度组(14例)。以上IBD患者均符合《炎症性肠病诊断和治疗的共识意见》(2018年北京)中的诊断标准。另外,以我院体检科同期健康体检人群193例作为正常对照组,收集病例组及对照组的年龄、身高、体重、性别、血常规相关指标(包括白细胞,血红蛋白,血小板,中性粒细胞计数、单核细胞、淋巴细胞计数),以及病例组的血沉(Erythrocyte sedimentation rate,ESR)、C-反应蛋白(C-reactive protein,CRP),腹部B超或CT或MRI,内镜报告等指标。完成病例组疾病活动度的分组,比较IBD组与对照组,UC组与CD组NLR、MLR、PLR等指标的差异,分别比较UC和CD患者轻度组、中度组及重度组间上述各项指标的差异,对NLR、MLR、PLR与ESR、CRP进行相关性分析。采用SPSS 25.0统计软件分析处理。计量资料经正态分布或方差齐性检验后,符合正态分布的连续变量用均数±标准差(x±s);符合偏态分布的计量资料使用中位数及四分位数间距(25%分位数,75%分位数),组间采用t检验或秩和检验;采用Pearson或Spearman相关性分析确定NLR、MLR、PLR与ESR、CRP的相关性;构建受试者工作特征曲线(ROC曲线),并计算曲线下面积(AUC)及其95%CI,P<0.05为差异有统计学意义。结果:1.IBD患者NLR、MLR以及PLR均显著高于对照组,UC组及CD组患者的NLR、MLR、PLR均明显高于对照组,差异均有统计学意义(P<0.05)。2.CD患者的NLR、PLR均高于UC组,差异均无统计学意义,UC组患者的MLR高于CD组,差异无统计学意义。3.CD患者轻度组、中度组的NLR、MLR、PLR均明显低于重度组,差异均具有统计学意义(P<0.05);轻度组的NLR低于中度组,差异无统计学意义;轻度组的MLR低于中度组,差异无统计学意义;轻度组的PLR明显低于中度组,差异有统计学意义(P<0.05)。4.UC患者轻度组NLR低于中度组,差异无统计学意义,低于重度组,差异有统计学差异(P<0.05),中度组NLR低于重度组,差异无统计学意义;轻度组MLR低于中度组、重度组,差异均无统计学意义,中度组MLR低于重度组,差异无统计学意义;轻度组PLR高于中度组,差异无统计学意义,低于重度组,差异无统计学意义,中度组PLR低于重度组,差异有统计学意义(P<0.05)5.IBD患者NLR、MLR、PLR与炎症指标ESR、CRP呈明显正相关(P<0.01);CD患者NLR、MLR、PLR与炎症指标ESR、CRP呈明显正相关(P<0.01);UC患者NLR与炎症指标ESR呈正相关(P<0.05),MLR、PLR与炎症指标ESR呈明显正相关(P<0.01),NLR、MLR与炎症指标CRP呈明显正相关(P<0.01),PLR与炎症指标CRP呈正相关(P<0.05)。6.NLR评估轻度CD、中度CD、重度CD的AUC分别为0.775、0.870、0.988,敏感性和特异性分别为0.725、0.753、0.929和0.803、0.881、0.969。MLR评估轻度CD、中度CD、重度CD的AUC为0.810、0.870、0.996,敏感性和特异性分别为0.569、0.704、0.821和0.907、0.896、0.902。PLR评估轻度CD、中度CD、重度CD的AUC为0.836、0.941、0.999,敏感性和特异性分别为0.686、0.840、0.920和0.943、0.948、0.956。7.NLR评估轻度UC、中度UC、重度UC的AUC分别为0.608、0.836、0.888,敏感性和特异性分别为0.800、0.692、0.708和0.575、0.819、0.979。MLR评估轻度UC、中度UC、重度UC的AUC为0.764、0.771、0.928,敏感性和特异性分别为0.700、0.769、0.875和0.798、0.725、0.938。PLR评估轻度UC的AUC为0.790、0.701、0.914,敏感性和特异性分别为0.700、0.538、0.875和0.808、0.912、0.917。结论:1.IBD患者NLR、MLR、PLR较健康者明显升高,且与ESR及CRP具有相关性。2.PLR在不同疾病活动度的CD中的差异有意义,PLR可作为评估CD病情活动度的指标。MLR、PLR是否能评估CD的病情活动度尚需进一步研究。PLR评估CD活动度具有较高的敏感性和特异性。3.NLR、MLR、PLR是否能评估UC的病情活动度尚需进一步研究。更多还原

【Abstract】 Background:Inflammatory bowel disease(IBD),mainly including Crohn’S disease(CD)and ulcerative colitis(UC),is a group of chronic immune disorders in intestine.IBD becomes a critical challenge in clinic with high frequency of relapse and poor prognosis.Patients with IBD suffer the disease with long term disease course,thus,it is urgent to develop clinical parameters to monitor disease activity of the patients.Currently,evaluation and diagnosis of IBD is performed by endoscopy and pathological examinations on biopsy,but those methods are costly and inconvenient to operate,and sometimes may have some complications such as bleeding,perforation,and poor patient compliance.Some other parameters of routine blood test including neutrophil to lymphocyte ratio(NLR),monocyte to lymphocyte ratio(MLR),and platelet to lymphocyte ratio(PLR)are associated with the pathogenesis of IBD and may be indicative of IBD disease activities,but the data from different groups exhibit high variation.The association between those parameters and IBD disease activities requires further studying.Objective:To study the correlation of routine blood test parameters including NLR,MLR,and PLR with disease activity of IBD patients.Method:The patients who were diagnosed with IBD for the first time in the Gastroenterology Department of our hospital from January 2016 to December 2020 were selected as the case group and divided into UC group(146 cases)and CD group(47 cases);UC group was divided according to the modified Mayo score Mild group(10 cases),moderate group(13 cases)and severe group(23 cases);CD group was divided into mild group(51 cases),moderate group(81 cases)and severe group(14cases).The above IBD patients meet the diagnostic criteria in the "Consensus on the Diagnosis and Treatment of Inflammatory Bowel Disease"(Beijing,2018).In addition,193 healthy people from the physical examination department of our hospital during the same period were selected as the normal control group.The age,height,weight,gender,and blood routine related indicators of the case group and the control group(including white blood cells,hemoglobin,platelets,neutrophil counts,Monocyte,lymphocyte count),Erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),abdominal B-ultrasound or CT or MRI,endoscopy report and other indicators in the case group.Complete the grouping of the disease activity of the case group,compare the differences in the indicators between the IBD group and the control group,the UC group and the CD group,and compare the differences in the indicators between the mild,moderate and severe groups of UC and CD patients,including NLR,MLR,PLR;analyze the correlation between NLR,MLR,PLR and ESR,CRP.SPSS 25.0 statistical software was used for analysis and processing.After the measurement data are tested for the normal distribution or the homogeneity of variance,the continuous variables conforming to the normal distribution are used as the mean ± standard deviation(±s);the measurement data conforming to the skewed distribution use the median and interquartile range(25 % Quantile,75% quantile),using t test or rank sum test between groups;using Pearson or Spearman correlation analysis to determine the correlation between NLR,MLR,PLR and ESR,CRP;construct receiver operating characteristic curve(ROC curve),and calculate the area under the curve(AUC)and its 95% CI.P<0.05 indicates that the difference is statistically significant.Result:1.The NLR,MLR,and PLR of IBD patients were significantly higher than those of the control group.The NLR,MLR,and PLR of patients in the UC group and CD group were significantly higher than those of the control group,and the differences were statistically significant(P<0.05).2.The NLR and PLR of CD patients were higher than those of the UC group,and the difference was not statistically significant.The MLR of patients in the UC group was higher than that of the CD group,and the difference was not statistically significant.3.The NLR,MLR,and PLR of the mild group and the moderate group of CD patients were significantly lower than those of the severe group,and the difference was statistically significant(P<0.05);the NLR of the mild group was lower than that of the moderate group,and the difference was not statistically significant Scientific significance;the MLR of the mild group was lower than that of the moderate group,and the difference was not statistically significant;the PLR of the mild group was significantly lower than that of the moderate group,and the difference was statistically significant(P<0.05).4.The NLR of the mild group of UC patients was lower than that of the moderate group,and the difference was not statistically significant.It was lower than that of the severe group,and the difference was statistically significant(P<0.05).The NLR of the moderate group was lower than that of the severe group,and the difference was not statistically significant.;The MLR of the mild group was lower than that of the moderate group and the severe group,and the difference was not statistically significant.The MLR of the moderate group was lower than the severe group,and the difference was not statistically significant;the PLR of the mild group was higher than that of the moderate group,and the difference was not statistically significant.Significance,lower than the severe group,the difference was not statistically significant,the PLR of the moderate group was lower than the severe group,the difference was statistically significant(P<0.05)5.NLR,MLR,and PLR in patients with IBD were significantly positively correlated with inflammation indicators ESR and CRP(P<0.01);NLR,MLR,and PLR in patients with CD were significantly positively correlated with inflammation indicators ESR and CRP(P<0.01);patients with UC NLR was positively correlated with inflammation index ESR(P<0.05),MLR,PLR and inflammation index ESR were significantly positively correlated(P<0.01),NLR,MLR and inflammation index CRP were significantly positively correlated(P<0.01),PLR and inflammation The index CRP was positively correlated(P<0.05).6.The AUCs of NLR for mild CD,moderate CD,and severe CD were 0.775,0.870,and 0.988,respectively.The sensitivity and specificity were 0.725,0.753,0.929 and 0.803,0.881,0.969.The AUC of MLR assessment of mild CD,moderate CD,and severe CD were 0.810,0.870,0.996,and the sensitivity and specificity were0.569,0.704,0.821 and 0.907,0.896,0.902,respectively.The AUC of PLR assessment of mild CD,moderate CD,and severe CD were 0.836,0.941,0.999,and the sensitivity and specificity were 0.686,0.840,0.920 and 0.943,0.948,0.956,respectively.7.The AUC of NLR assessment of mild UC,moderate UC,and severe UC were0.608,0.836,0.888,and the sensitivity and specificity were 0.800,0.692,0.708 and0.575,0.819,0.979,respectively.The AUC of MLR assessment of mild UC,moderate UC,and severe UC were 0.764,0.771,0.928,and the sensitivity and specificity were 0.700,0.769,0.875 and 0.798,0.725,0.938,respectively.The AUC of PLR assessment of mild UC was 0.790,0.701,0.914,and the sensitivity and specificity were 0.700,0.538,0.875 and 0.808,0.912,0.917,respectively.Conclusion:1.The NLR,MLR,and PLR of IBD patients are significantly higher than those of healthy people,and are related to ESR and CRP.2.The difference of PLR in CD with different disease activity is significant,and PLR can be used as an index to evaluate the disease activity of CD.Whether MLR and PLR can assess the disease activity of CD needs further research.PLR has high sensitivity and specificity in evaluating CD activity.3.Whether NLR,MLR,and PLR can assess the disease activity of UC needs further research.更多还原