Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario San Cecilio, Granada, Spain.
Cytokine. 2013 Feb;61(2):595-601. doi: 10.1016/j.cyto.2012.10.009. Epub 2012 Nov 16.
This paper investigates serum levels of interleukin 10 (IL-10) and interleukin 6 (IL-6) in patients with chronic hepatitis C genotype 1 (CHC-GT1), the relation of each with clinical and virological characteristics, how they affect the response to combined therapy and their relation with the IL28B polymorphisms rs12979860. Serum level expression and the polymorphism of IL-10, IL-6 and IL28B were determined in 138 CHC-GT1 patients, treated with pegylated interferon/ribavirin (pegIFN-α/RBV) for 48 weeks, in the following samples: baseline, week-12 (during treatment) and week-72 (post-treatment). 77 patients (56%) presented Sustained Virological Response (SVR) and 61 (44%) were non-SVR. Multivariate logistic regression showed that age ≤ 40 years (aOR=3.7, 95%CI=1.5-8.9, P=0.004), low activity of gamma glutamyl transferase (GGT) (aOR=0.9, 95%CI=0.98-0.99, P=0.028), CC genotype of IL28B polymorphism (aOR=2.7, 95%CI=1.0-7.2, P=0.044) and low IL-6 (aOR=0.5, 95%CI=0.3-1.0, P=0.038) were predictor factors of virological response. In all patients, following treatment, IL-6 decreased at week-12 (P=0.004) from baseline and had returned to basal values at week-72. Serum IL-10 concentration was significantly decreased at week-72 only in SVR patients (P ≤ 0.001). When patients were stratified by IL28B polymorphisms rs12979860 CC vs non-CC patients, a statistically significant decrease in IL-10 at week-72 in both groups was observed (P=0.003 and P ≤ 0.001, respectively). None of the polymorphisms of IL-10 or IL-6 studied were associated with SVR.
CC genotype of IL28B and low IL-6 serum concentration are factors associated independently with SVR. Moreover, decreased IL-10 at week-72 is associated with SVR in both CC and non-CC patients, and both factors are important to determine the effectiveness of treatment.
本研究旨在探讨慢性丙型肝炎基因型 1 （CHC-GT1）患者血清白细胞介素 10 （IL-10）和白细胞介素 6 （IL-6）水平，及其与临床和病毒学特征的关系，以及它们如何影响联合治疗的反应，并与 IL28B 多态性 rs12979860 相关。方法：采用聚合酶链反应技术检测 138 例 CHC-GT1 患者的 IL-10、IL-6 和 IL28B 基因多态性。这些患者均接受聚乙二醇干扰素/利巴韦林（pegIFN-α/RBV）治疗 48 周，分别在基线、第 12 周（治疗期间）和第 72 周（治疗后）采集样本。结果：77 例（56%）患者获得持续病毒学应答（SVR），61 例（44%）患者未获得 SVR。多因素逻辑回归分析显示，年龄≤40 岁（比值比[OR] = 3.7，95%置信区间[CI] = 1.5-8.9，P = 0.004）、γ谷氨酰转移酶（GGT）活性低（OR = 0.9，95%CI = 0.98-0.99，P = 0.028）、IL28B 多态性 CC 基因型（OR = 2.7，95%CI = 1.0-7.2，P = 0.044）和低 IL-6（OR = 0.5，95%CI = 0.3-1.0，P = 0.038）是病毒学应答的预测因素。在所有患者中，治疗后第 12 周（P = 0.004）时血清 IL-6 水平下降，并在第 72 周时恢复至基线水平。仅在 SVR 患者中，第 72 周时血清 IL-10 浓度显著下降（P ≤ 0.001）。根据 IL28B 多态性 rs12979860 CC 与非 CC 患者进行分层，两组患者在第 72 周时均观察到 IL-10 显著下降（P = 0.003 和 P ≤ 0.001）。研究中未发现 IL-10 或 IL-6 的任何多态性与 SVR 相关。结论：IL28B 的 CC 基因型和低血清 IL-6 浓度是与 SVR 独立相关的因素。此外，第 72 周时 IL-10 下降与 CC 和非 CC 患者的 SVR 相关，这两个因素对于确定治疗效果很重要。
