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IL28B 多态性、IP-10 和病毒载量可预测慢性丙型肝炎治疗的病毒学应答。

IL28B polymorphisms, IP-10 and viral load predict virological response to therapy in chronic hepatitis C.

机构信息

Clinic of Gastroenterology, Department of Medicine, University of Verona, Piazzale L.A. Scuro 10, Verona, Italy.

出版信息

Aliment Pharmacol Ther. 2011 May;33(10):1162-72. doi: 10.1111/j.1365-2036.2011.04635.x. Epub 2011 Mar 28.

Abstract

BACKGROUND

Hepatitis C virus (HCV) is a major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma and the identification of the predictors of response to antiviral therapy is an important clinical issue.

AIM

To determine the independent contribution of factors including IL28B polymorphisms, IFN-gamma inducible protein-10 (IP-10) levels and the homeostasis model assessment of insulin resistance (HOMA-IR) score in predicting response to therapy in chronic hepatitis C (CHC).

METHODS

Multivariate analysis of factors predicting rapid (RVR) and sustained (SVR) virological response in 280 consecutive, treatment-naive CHC patients treated with peginterferon alpha and ribavirin in a prospective multicentre study.

RESULTS

Independent predictors of RVR were HCV RNA <400 000 IU/mL (OR 11.37; 95% CI 3.03-42.6), rs12980275 AA (OR 7.09; 1.97-25.56) and IP-10 (OR 0.04; 0.003-0.56) in HCV genotype 1 patients and lower baseline γ-glutamyl-transferase levels (OR=0.02; 0.0009-0.31) in HCV genotype 3 patients. Independent predictors of SVR were rs12980275 AA (OR 9.68; 3.44-27.18), age <40 years (OR=4.79; 1.50-15.34) and HCV RNA <400 000 IU/mL (OR 2.74; 1.03-7.27) in HCV genotype 1 patients and rs12980275 AA (OR=6.26; 1.98-19.74) and age <40 years (OR 5.37; 1.54-18.75) in the 88 HCV genotype 1 patients without a RVR. RVR was by itself predictive of SVR in HCV genotype 1 patients (OR 33.0; 4.06-268.32) and the only independent predictor of SVR in HCV genotype 2 (OR 9.0, 1.72-46.99) or genotype 3 patients (OR 7.8, 1.43-42.67).

CONCLUSIONS

In HCV genotype 1 patients, IL28B polymorphisms, HCV RNA load and IP-10 independently predict RVR. The combination of IL28B polymorphisms, HCV RNA level and age may yield more accurate pre-treatment prediction of SVR. HOMA-IR score is not associated with viral response.

摘要

背景

丙型肝炎病毒(HCV)是慢性肝病、肝硬化和肝细胞癌的主要病因,鉴定抗病毒治疗应答的预测因子是一个重要的临床问题。

目的

确定包括 IL28B 多态性、干扰素-γ诱导蛋白-10(IP-10)水平和稳态模型评估的胰岛素抵抗(HOMA-IR)评分在内的因素对慢性丙型肝炎(CHC)患者治疗应答的独立预测作用。

方法

对 280 例连续、未经治疗的 CHC 患者进行前瞻性多中心研究,这些患者接受聚乙二醇干扰素α和利巴韦林治疗,采用多变量分析预测快速病毒学应答(RVR)和持续病毒学应答(SVR)的因素。

结果

HCV 基因型 1 患者中 RVR 的独立预测因子为 HCV RNA<400000IU/ml(OR 11.37;95%CI 3.03-42.6)、rs12980275AA(OR 7.09;1.97-25.56)和 IP-10(OR 0.04;0.003-0.56),而 HCV 基因型 3 患者中则为基线 γ-谷氨酰转移酶水平较低(OR=0.02;0.0009-0.31)。HCV 基因型 1 患者中 SVR 的独立预测因子为 rs12980275AA(OR 9.68;3.44-27.18)、年龄<40 岁(OR=4.79;1.50-15.34)和 HCV RNA<400000IU/ml(OR 2.74;1.03-7.27),而在 88 例无 RVR 的 HCV 基因型 1 患者中,SVR 的独立预测因子为 rs12980275AA(OR 6.26;1.98-19.74)和年龄<40 岁(OR 5.37;1.54-18.75)。在 HCV 基因型 1 患者中,RVR 本身是 SVR 的预测因子(OR 33.0;4.06-268.32),而在 HCV 基因型 2(OR 9.0,1.72-46.99)或基因型 3 患者(OR 7.8,1.43-42.67)中则是唯一的 SVR 预测因子。

结论

在 HCV 基因型 1 患者中,IL28B 多态性、HCV RNA 载量和 IP-10 独立预测 RVR。IL28B 多态性、HCV RNA 水平和年龄的组合可能会对 SVR 产生更准确的预测。HOMA-IR 评分与病毒应答无关。

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