Fischer Josiane, Silva Telma Erotides, Soares E Silva Pedro Eduardo, Colombo Bruno Silveira, Silva Mariana Costa, Wildner Letícia Muraro, Bazzo Maria Luiza, Rateke Elayne Cristina Morais, Frode Tania Silvia, Mello Silvana Vigil de, Rosa Júlia S, Dantas-Correa Esther Buzaglo, Narciso-Schiavon Janaína Luz, Schiavon Leonardo Lucca
Division of Gastroenterology, Federal University of Santa Catarina, Brazil.
Department of Clinical Analysis, Federal University of Santa Catarina, Brazil.
Cytokine. 2017 Mar;91:162-169. doi: 10.1016/j.cyto.2016.12.017. Epub 2017 Jan 9.
Although both pro- and anti-inflammatory circulating cytokines are known to be elevated in liver cirrhosis, its clinical significance is not completely recognized. Our aim was to evaluate the prognostic significance of circulating cytokines interleukin (IL)-6, IL-17 and IL-10 in different stages of cirrhosis.
This prospective study included two cohorts: (1) stable cirrhosis attended in the Outpatient Clinic (n=118), and (2) subjects hospitalized for acute decompensation (AD) (n=130). Thirty healthy subjects served as control group.
Patients with cirrhosis exhibited higher levels of cytokines as compared to controls. In stable cirrhosis, during a median follow-up of 17months, liver-related events occurred in 26 patients. Higher IL-10 levels and Child-Pugh B/C were independently associated with reduced event-free survival. In AD cohort, death after 90days of follow-up occurred in 39 patients and was independently associated with ascites, higher IL-6 and model for end-stage liver disease. IL-6 levels also showed higher AUROC than CRP for predicting bacterial infection in the AD cohort (0.831±0.043vs. 0.763±0.048, respectively). IL-17 decreased at third day of hospitalization only in patients who progressed to death. Higher IL-6 levels were observed in acute-on-chronic liver failure (ACLF) patients even in the absence of bacterial infection whereas IL-10 was higher only in subjects with infection-related ACLF. Higher IL-10 and IL-17 levels were associated with progression to death in ACLF.
The pattern of immune response seems to vary according to the phase of cirrhosis and is related to prognosis, from stable disease to ACLF.
尽管已知促炎和抗炎循环细胞因子在肝硬化中均升高，但其临床意义尚未完全明确。我们的目的是评估循环细胞因子白细胞介素（IL）-6、IL-17和IL-10在肝硬化不同阶段的预后意义。
这项前瞻性研究包括两个队列：（1）门诊就诊的稳定期肝硬化患者（n = 118），以及（2）因急性失代偿（AD）住院的患者（n = 130）。30名健康受试者作为对照组。
与对照组相比，肝硬化患者的细胞因子水平更高。在稳定期肝硬化患者中，中位随访17个月期间，26例患者发生了肝脏相关事件。较高的IL-10水平和Child-Pugh B/C分级与无事件生存期缩短独立相关。在AD队列中，随访90天后39例患者死亡，且死亡与腹水、较高的IL-6水平和终末期肝病模型独立相关。在AD队列中，IL-6水平预测细菌感染的受试者工作特征曲线下面积（AUROC）也高于C反应蛋白（CRP）（分别为0.831±0.043和0.763±0.048）。仅在进展至死亡的患者中，住院第三天IL-17水平下降。即使在无细菌感染的情况下，慢性急性肝衰竭（ACLF）患者中也观察到较高的IL-6水平，而仅在与感染相关的ACLF患者中IL-10水平较高。较高的IL-10和IL-17水平与ACLF患者进展至死亡相关。
免疫反应模式似乎因肝硬化阶段而异，并且与从稳定期疾病到ACLF的预后相关。
