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IL28B 多态性与基因型 4 慢性丙型肝炎患者的治疗反应相关。

IL28B polymorphism is associated with treatment response in patients with genotype 4 chronic hepatitis C.

机构信息

Hepatology Department, AP-HP, University Paris Diderot 7 and INSERM U773, CRB3, Beaujon Hospital, Clichy, France.

出版信息

J Hepatol. 2012 Mar;56(3):527-32. doi: 10.1016/j.jhep.2011.09.008. Epub 2011 Sep 25.

Abstract

BACKGROUND & AIMS: Polymorphisms in the region of the interleukin (IL)28B gene have been associated with pegylated-interferon (PEG-IFN) and ribavirin treatment response mainly in genotype 1 HCV infections. However, there are few data on HCV genotype 4 (HCV-4) infection. We evaluated, in a unique well-characterized cohort of HCV-4 patients, the association of IL28B polymorphism with response to treatment or liver disease severity.

METHODS

This study included 164 HCV-4 patients from different ethnic groups (Egyptian, European, and Sub-Saharan African). Among these patients, 82 were studied for response and 160 for disease severity. Free DNA extracted from all the 164 patient's serum samples was analyzed by direct sequencing of the SNP rs12979860 of IL28B. Genetic and bio-clinical features from patients having sustained virological response (43 SVR patients) and from those who did not respond to treatment or had a relapse after the end of the treatment (39 NR patients) were compared. IL28B polymorphism was compared between the 78 patients with mild fibrosis (Metavir score F0-F1) and the 82 with advanced fibrosis (F2-F4).

RESULTS

Our data showed a better treatment response rate of the C allele of the IL28B gene SNP rs12979860 (p=0.0008). The response rates were 81.8%, 46.5%, and 29.4% for genotype CC, CT, and TT, respectively. No significant relationship was found between rs12979860 and the severity of the disease.

CONCLUSIONS

The SNP rs12979860 is strongly associated with SVR in patients infected with HCV-4, but not with liver disease severity. Analysis of IL28B genotype might be used to guide treatment for these patients.

摘要

背景与目的

白细胞介素(IL)28B 基因区域的多态性与聚乙二醇干扰素(PEG-IFN)和利巴韦林治疗反应有关,主要与基因型 1 HCV 感染有关。然而,关于 HCV 基因型 4(HCV-4)感染的数据很少。我们在一个独特的、特征明确的 HCV-4 患者队列中评估了 IL28B 多态性与治疗反应或肝脏疾病严重程度的关系。

方法

本研究包括来自不同种族(埃及、欧洲和撒哈拉以南非洲)的 164 名 HCV-4 患者。其中 82 例患者接受了治疗反应研究,160 例患者接受了疾病严重程度研究。从所有 164 名患者的血清样本中提取游离 DNA,通过直接测序分析 IL28B 的 SNP rs12979860。比较持续病毒学应答(43 例 SVR 患者)和未应答或治疗结束后复发(39 例 NR 患者)患者的遗传和临床特征。比较 78 例纤维化程度较轻(Metavir 评分 F0-F1)和 82 例纤维化程度较重(F2-F4)患者的 IL28B 多态性。

结果

我们的数据显示,IL28B 基因 SNP rs12979860 的 C 等位基因的治疗反应率更好(p=0.0008)。基因型 CC、CT 和 TT 的反应率分别为 81.8%、46.5%和 29.4%。rs12979860 与疾病严重程度之间无显著关系。

结论

SNP rs12979860 与 HCV-4 感染患者的 SVR 密切相关,但与肝脏疾病严重程度无关。分析 IL28B 基因型可能用于指导这些患者的治疗。

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