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白细胞介素-6作为肝硬化患者细菌性脓毒症的早期诊断标志物

Interleukin-6 as an early diagnostic marker for bacterial sepsis in patients with liver cirrhosis.

作者信息

Lin Su, Huang Zhongtao, Wang Mingfang, Weng Zhiyuan, Zeng Dawu, Zhang Yanliang, Zhu Yueyong, Jiang Jiaji

机构信息

Liver Research Center, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350005, China.

Department of Gastroenterology, The First Hospital of Putian City, The training hospital of Fujian Medical University, Putian, Fujian, 351100, China.

出版信息

J Crit Care. 2015 Aug;30(4):732-8. doi: 10.1016/j.jcrc.2015.03.031. Epub 2015 Apr 8.

Abstract

OBJECTIVE

Liver cirrhosis is associated with frequent bacterial infections that increase the mortality rate. However, the early diagnosis and treatment of these infections are often difficult. In this retrospective-prospective observational study, the serum levels of interleukin-6 (IL-6) and procalcitonin (PCT) were measured in 233 cirrhotic patients to evaluate the early diagnostic and prognostic values of IL-6 and PCT for cirrhotic patients.

METHODS

Cirrhotic patients admitted to the Liver Research Center of the First Affiliated Hospital of Fujian Medical University between 1 October 2012 and 30 June 2014 were enrolled. They showed no evidence of infection on admission, and all had first onset of fever and met the systemic inflammatory response syndrome criteria 72 hours after admission. The serum IL-6 and PCT levels were determined on admission, at the onset of fever (0 hour) and 24 and 48 hours after fever onset.

RESULTS

A total of 233 cirrhotic patients, including 183 men and 50 women, with a median age of 56 (46-65) years were enrolled. A training group of 159 patients was retrospectively enrolled from 1 October 2012 to 31 December 2013, and a validation group of 74 patients was prospectively enrolled from 1 January 2014 to 30 June 2014. Among these patients, 134 were diagnosed with bacterial sepsis, 96 of whom were in the training group and 38 of whom were in the validation group; infections were ultimately ruled out in 99 patients: 63 training patients and 36 validation patients. At 0 hour, the IL-6 and PCT levels as well as the proportion of neutrophils were much higher in septic patients than in nonseptic ones. The IL-6 level and proportion of neutrophils peaked upon the onset of fever, 24 hours before the PCT levels and white blood cell count, and then sharply declined. The area under the receiver operating characteristic curve of IL-6 for diagnosing sepsis was largest at the onset of fever (area under the receiver operating characteristic curve, 0.983; 95% confidence interval, 0.967-0.999). The threshold of IL-6 for diagnosis was 135 pg/mL, with a sensitivity of 94.8% and a specificity of 93.7%. These diagnostic values were also confirmed in the validation group, with a sensitivity of 97.4% and specificity of 80.6%. Eleven (11.5%) patients died, and 85 (88.5%) patients recovered in the sepsis group of training patients after a 4-week follow-up. The IL-6 level was significantly higher in the nonsurvival group than that in the survival group (1813.00 vs 472.10 pg/mL, P = .004) at the onset of sepsis. The cutoff value for predicting prognosis was 1105 pg/mL, with a sensitivity of 81.8% and a specificity of 76.5%.

CONCLUSIONS

The serum IL-6 levels increased earlier than the PCT in septic cirrhotic patients. The direct measurement of the serum IL-6 level can help to rapidly detect bacterial infection, thus allowing for early therapeutic decisions and prognostic predictions.

摘要

目的

肝硬化常伴有频繁的细菌感染,这会增加死亡率。然而,这些感染的早期诊断和治疗往往很困难。在这项回顾性-前瞻性观察研究中,对233例肝硬化患者的血清白细胞介素-6(IL-6)和降钙素原(PCT)水平进行了检测,以评估IL-6和PCT对肝硬化患者的早期诊断和预后价值。

方法

纳入2012年10月1日至2014年6月30日期间入住福建医科大学附属第一医院肝病研究中心的肝硬化患者。他们入院时无感染证据,且均首次发热,并在入院72小时后符合全身炎症反应综合征标准。在入院时、发热开始时(0小时)以及发热开始后24小时和48小时测定血清IL-6和PCT水平。

结果

共纳入233例肝硬化患者,其中男性183例,女性50例,中位年龄为56(46 - 65)岁。回顾性纳入2012年10月1日至2013年12月31日的159例患者作为训练组,前瞻性纳入2014年1月1日至2014年6月30日的74例患者作为验证组。这些患者中,134例被诊断为细菌性败血症,其中训练组96例,验证组38例;99例患者最终排除感染:训练组63例,验证组36例。在0小时时,败血症患者的IL-6和PCT水平以及中性粒细胞比例均显著高于非败血症患者。IL-6水平和中性粒细胞比例在发热开始时达到峰值,比PCT水平和白细胞计数提前24小时,然后急剧下降。IL-6诊断败血症的受试者操作特征曲线下面积在发热开始时最大(受试者操作特征曲线下面积,0.983;95%置信区间,0.967 - 0.999)。IL-6的诊断阈值为135 pg/mL,敏感性为94.8%,特异性为93.7%。这些诊断价值在验证组中也得到证实,敏感性为97.4%,特异性为80.6%。经过4周随访,训练组败血症患者中11例(11.5%)死亡,85例(88.5%)康复。在败血症开始时,非存活组的IL-6水平显著高于存活组(1813.00 vs 472.10 pg/mL,P = 0.004)。预测预后的截断值为1105 pg/mL,敏感性为81.8%,特异性为76.5%。

结论

在败血症肝硬化患者中,血清IL-6水平比PCT升高更早。直接检测血清IL-6水平有助于快速检测细菌感染,从而做出早期治疗决策和预后预测。

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