WBC、PCT及IL-6水平对肾综合征出血热患者病情严重程度的预测价值
Prediction Value of WBC, PCT and IL-6 Levels in the Severity of Hemorrhagic Fever with Renal Syndrome
摘要: 目的：探讨白细胞计数(WBC)、降钙素原(procalcitonin, PCT)和白细胞介素-6 (interleukin-6, IL-6)水平对肾综合征出血热患者病情严重程度的预测价值。方法：本研究选取2021年至2023年在空军军医大学第二附属医院急诊科确诊为HFRS患者为研究对象，共118例。参照《肾综合征出血热诊疗陕西省专家共识》(2019)，将患者分为轻型、中型、重型和危重型，其中将轻型与中型定义为轻症组(n = 50)，重型与危重型定义为重症组(n = 68)。比较WBC、PCT和IL-6水平在不同组间的表达差异；分析WBC、PCT和IL-6预测HFRS病情严重程度的敏感度及特异度。结果：重症组血清WBC、PCT和IL-6水平均高于轻症组，差异均有统计学意义(P < 0.050)。进行logistic回归分析筛查出PCT和IL-6是患者进展为危重症的独立影响因子(均P < 0.050)。进一步分析PCT、IL-6及其联合指标对重症HFRS预警效能的曲线下面积(area under curve, AUC)分别为0.872，0.768，最佳阈值分别为8.220 ng/ml、42.670 pg/ml，联合检测AUC为0.883，敏感度为36.8%，特异度为90.0%，优于单个实验室检查指标的检测。结论：WBC、PCT和IL-6能早期预测HFRS病情严重程度，其中的PCT和IL-6水平为独立危险因素，其联合指标有更好的特异度。
Abstract: Objective: To investigate the value of leukocyte count (WBC), procalcitonin (PCT) and interleukin-6 (IL-6) levels in predicting the severity of hemorrhagic fever with renal syndrome. Methods: A total of 118 patients diagnosed with HFRS in the emergency Department of the Second Affiliated Hospital of Air Force Med Prediction value of WBC, PCT and IL-6 levels in the severity of hemorrhagic fever with renal syndromeical University from 2021 to 2023 were selected as the study objects. According to the Expert Consensus on the Diagnosis and Treatment of hemorrhagic fever with renal Syndrome in Shaanxi Province (2019), the patients were divided into mild, medium, severe and critical types, in which the mild and medium types were defined as the mild group (n = 50), and the severe and critical types as the severe group (n = 68). The expression of WBC, PCT and IL-6 in different groups were compared. The sensitivity and specificity of WBC, PCT and IL-6 in predicting the severity of HFRS were analyzed. Results: The levels of serum WBC, PCT and IL-6 in severe group were higher than those in mild group, with statistical significance (P < 0.050). Logistic regression analysis showed that PCT and IL-6 were independent factors for progression to critical illness (both P < 0.050). The area under curve (AUC) of PCT, IL-6 and their combined indicators for warning severe HFRS was 0.872 and 0.768, respectively, and the optimal threshold was 8.220 ng/ml and 42.670 pg/ml, respectively, and the AUC of combined detection was 0.883. The sensitivity was 36.8%, and the specificity was 90.0%, which was better than that of a single laboratory test index. Conclusion: WBC, PCT and IL-6 can predict the severity of HFRS early. PCT and IL-6 levels are independent risk factors, and their combined indexes have better specificity.
文章引用：杨琴琴, 郭锦煜. WBC、PCT及IL-6水平对肾综合征出血热患者病情严重程度的预测价值[J]. 临床医学进展, 2024, 14(9): 1012-1017. https://doi.org/10.12677/acm.2024.1492560

1. 引言

肾综合征出血热(hemorrhagic fever with renal syndrome, HFRS)是一种全球分布的急性自然疫源性疾病，其中我国是受肾综合征出血热危害最为严重的国家[1]。据文献报道[2]，自1950年至2020年底，中国已累计确诊HFRS患者1,688,031例，其中死亡48,260例，每年病死率波动于0.60%~13.97%，总病死率达2.86%。HFRS病情进展迅速，常因为误诊或未能识别重症错失最佳治疗时间，因此早期识别重症HFRS是成功诊疗的关键环节。重症HFRS常伴有严重的全身炎症反应性疾病，其病理生理变化是主要是血管内皮受损导致的血管通透性增加和出血，是该病发生发展过程与临床表现的基础[3]-[5]。已有不少研究指出WBC、PCT与HFRS病情有关，其中王惠琦[6]等人以227例HFRS患者为研究对象，发现PCT和NEC指标，在一定程度上可作为判定患者分期的依据，WBC和NEC指标在一定程度上可作为判定患者分型的依据。陈文静[7]研究发现危重型HFRS患者，CRP和PCT检测结果显著高于轻型、中型和重型患者(P < 0.05)。但临床上对IL-6水平的研究甚少。本研究回顾分析了50例轻症HFRS患者、68例HFRS重症患者中炎性指标WBC、PCT和IL-6水平的变化情况，探讨这些指标在HFRS患者病情严重程度的预测价值，为早期诊疗HFRS提供参考依据。

2. 对象与方法

2.1. 研究对象

本研究对2021年至2023年就诊空军军医大学第二附属医院急诊科的HFRS患者进行回顾性分析。纳入标准：以《肾综合征出血热防治专家共识》(2021) [8]中的临床诊断病例和确诊病例为标准。排除标准：合并其他病毒性感染病、细菌性感染、血液系统疾病、严重肝脏及肾脏疾病、自身免疫性疾病、肿瘤性疾病及发病前存在严重免疫缺陷及关键指标缺失的病例。最终118例患者纳入该研究，其中，男94例(79.7%)，女24例(20.3%)，平均年龄(43.38 ± 17.63)岁。参照《肾综合征出血热诊疗陕西省专家共识》(2019) [9]，将患者分为轻型、中型、重型和危重型，其中将轻型与中型定义为轻症组，重型与危重型定义为重症组。

2.2. 研究方法

收集118例HFRS患者的WBC、PCT和IL-6数据，以患者入院时第1次检测结果为统计信息。白细胞计数(WBC)采用日本希森美康全自动分析以及配套试剂，降钙素原(PCT)采用美国赛默飞时间分辨荧光免疫分析仪检测。

2.3. 统计学方法

采用SPSS 25.0软件进行统计学分析，不符合正态分布计量资料用用中位数(四分位间距)表示，组间比较采用非参数KruskalWallisH检验；计数资料以例数和百分数表示，组间比较采用χ2检验；应用Spearman相关性分析指标之间的相关性；应用Logistic回归分析筛选出HFRS患者病情严重程度的独立危险因素；应用ROC曲线分析参数对病情严重程度的预测价值，计算AUC和95%的可信区间(confidence interval, CI)，P < 0.05表示差异有统计学意义。

3. 结果

3.1. HFRS轻症组与重症组年龄、性别、WBC、PCT和IL-6水平比较

HFRS重症组WBC、PCT和IL-6水平高于轻症组，差异均有统计学意义(P < 0.050)；患者年龄和性别水平在轻、重症组间上无统计学差异(P > 0.050)，见表1。

Table 1. Comparison of age, sex, WBC, PCT and IL-6 levels between mild HFRS group and severe HFRS group

表1. HFRS轻症组与重症组年龄、性别、WBC、PCT和IL-6水平比较

指标

 轻症组

 重症组(n = 68)

 χ2/Z

 P
男(例，%)

 37 (74.00%)

 57 (83.82%)

 1.716

 0.190
年龄(岁)

 42.00 (29)

 45.00 (26)

 −0.101

 0.920
WBC (×109/L)

 10.67 (9.23)

 15.67 (13.19)

 −2.946

 0.003
PCT (ng/ml)

 1.86 (4.43)

 16.85 (31.12)

 −6.889

 0.000
IL-6 (pg/ml)

 20.895 (31.02)

 45.425 (70.47)

 −4.959

 0.000

3.2. WBC、PCT和IL-6水平与临床分型(轻/重症)相关性

WBC水平与临床分析即病情严重程度成弱正相关(P < 0.05)，rs值为0.272；PCT水平与病情严重程度成强正相关(P < 0.05)，rs值为0.637；IL-6水平与病情严重程度成中等正相关(P < 0分析0.05)，rs值为0.458。见表2。

Table 2. Correlation between WBC, PCT and IL-6 levels and disease types

表2. WBC、PCT和IL-6水平与病情分型相关性

指标

 rs值

 P
WBC

 0.272

 0.003
PCT

 0.637

 0.000
IL-6

 0.458

 0.000

3.3. WBC、PCT和IL-6水平在重症HFRS的Logistic回归分析情况

以HFRS临床分型(轻/重症)为因变量，以WBC、PCT和IL-6水平为自变量，进行二元logistic回归分析筛查得出PCT、IL-6水平是患者进展危重症的独立影响因子(均P < 0.050)。见表3。

Table 3. Logistic regression analysis of WBC, PCT and IL-6 levels in severe HFRS

表3. WBC、PCT和IL-6水平在重症HFRS的Logistic回归分析

指标

 B

 SE

 P

 Wald值

 OR值

 95% CI
WBC

 0.048

 0.030

 0.107

 2.602

 1.049

 (0.990, 1.113)
PCT

 0.106

 0.029

 0.000

 12.904

 1.112

 (1.049, 1.178)
IL-6

 0.023

 0.010

 0.027

 4.921

 1.023

 (1.003, 1.044)
常数

 −2.377

 0.595

 0.000

 15.948

 0.093

 (-, -)

3.4. PCT、IL-6水平及其联合指标对重症HFRS患者预测的ROC曲线分析

Figure 1. Subject operating characteristic curves of PCT, IL-6 and combined tests in the diagnosis of severe HFRS

图1. PCT、IL-6及联合检测在诊断重症HFRS的受试者操作特征曲线

PCT、IL-6水平及其联合指标对重症HFRS患者预测的ROC曲线下面积AUC分别为0.872，0.768，最佳阈值分别为8.220 ng/ml、42.670 pg/ml，联合检测AUC为0.883，敏感度为36.8%，特异度为90.0%，优于单个实验室检查指标的检测(见图1，表4)。

Table 4. ROC curve analysis of PCT, IL-6 levels and their combined indexes for predicting patients with severe HFRS

表4. PCT、IL-6水平及其联合指标对重症HFRS患者预测的ROC曲线分析

实验室指标

 最佳阈值

 AUC

 P

 灵敏度(%)

 特异度(%)

 95% CI
下限

 上限
PCT

 8.220

 0.872

 <0.001

 75.0%

 86.0%

 0.810

 0.935
IL-6

 42.670

 0.768

 <0.001

 55.9%

 86.0%

 0.685

 0.851
联合检测

 18.065

 0.883

 <0.001

 36.8%

 90.0%

 0.825

 0.941

4. 讨论

肾综合征出血热是由汉坦病毒科正汉坦病毒属病毒引起的，以啮齿类动物为主要传染源的自然疫源性疾病。汉坦病毒可直接破坏受感染细胞的功能和结构，诱发固有免疫反应和适应性免疫反应，B细胞和T细胞反应以及多种细胞因子、炎症因子都参与了病理生理过程[10] [11]。其中炎症因子风暴在重症患者的发病中发挥了重要作用。为了早期更好的识别重症HFRS患者，本研究对临床上常用的炎性指标WBC、PCT及IL-6进行了研究。

WBC指标是临床上发热患者就诊或初诊时判断细菌感染的基本特征，其敏感性高，特异性不强，本研究表明WBC水平不是患者进展危重症的独立危险因素(P > 0.05)，这与既往研究相符[12]。PCT常年被广泛用于监测细菌感染的指标，对脓毒症、重症肺炎感染有很好的预测价值[13]。王庆增等人[14]通过分析117例肺炎患者实验室数据，发现PCT、RDW水平变化在重症肺炎患者血清中呈高水平表达，且与感染程度、器官功能状态相关，联合检测对重症肺炎患者病情程度诊断、临床治疗及疾病转归有重要指导作用结论。近年也有相关研究表明，TNF-α和IL-6无细菌感染的情况下也可诱导PCT的产生，其升高水平与感染的严重程度呈正相关，对临床监测病情变化、指导用药均具有重要意义[15]。本研究表明HFRS患者血清PCT水平与疾病的严重程度呈正相关，这与既往研究一致。IL-6是常见的促炎因子，具有诱导炎症细胞聚集、促进大量炎症因子释放的作用，其水平升高对感染机体的早期诊断、指导治疗和预后评价等方面有重要作用[16]。本研究表明重症组IL-6水平水平均高于轻症组，且与病情严重程度呈正相关，通过二元logistic回归分析筛查得出PCT、IL-6水平是患者进展危重症的独立危险因素(P < 0.05)，其联合指标更具有特异性。

综上所述，WBC、PCT和IL-6能早期预测HFRS病情严重程度，其中的PCT和IL-6水平为独立危险因素，其联合指标有更好的特异度。本研究有一定局限性，首先，样本量较少，分布不均一，结果可能存在偏差；其次，只分析了炎症指标，缺少对生化指标的分析，且未对炎症指标动态分析。未来需要进行多中心、大样本、前瞻性研究随机对照研究，来明确WBC、PCT、IL-6在确诊重症HFRS的预测价值。

NOTES

*通讯作者。

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