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白细胞介素 28B 多态性在聚乙二醇干扰素治疗 HBeAg 阴性慢性乙型肝炎患者中的作用。

Role of IL28-B polymorphisms in the treatment of chronic hepatitis B HBeAg-negative patients with peginterferon.

机构信息

Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.

Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.

出版信息

Antiviral Res. 2014 Feb;102:35-43. doi: 10.1016/j.antiviral.2013.11.014. Epub 2013 Dec 4.

Abstract

Interleukin (IL)28-B polymorphism has been related to interferon response in the treatment of hepatitis C, but its role in chronic hepatitis B (CHB) therapy is still poorly understood. We aimed to investigate the effect of IL28-B polymorphisms in the treatment with pegylated-interferon (PEG-IFN) of patients with CHB. We retrospectively analyzed 190 patients with chronic hepatitis B e antigen (HBeAg) negative, genotype A (22%), B (12%), C (10%), D (33%), E (20%), treated with PEG-IFN alfa-2a for 48weeks; genotype analysis was performed for IL28-B polymorphisms rs12979860, rs8099917 and rs12980275 according to virological, serological and biochemical response. During 2years of follow-up 12 patients (6.3%) cleared hepatitis B surface antigen (HBsAg) with seroconversion, 40 (21%) obtained a negative viral load and 104 (54.7%) gained a biochemical response. We found a difference of distribution of rs12979860 CC genotype among different ethnicity (p=0.013). Rs12979860 CC genotype was significantly associated with serological and virological response (p<0.001); rs8099917 TT and rs12980275 AA genotypes were mostly related with virological response (p<0.001). In multivariate logistic analysis rs12979860 CC was predictive of virological response (OR=4.290; CI=1.589-11.580, p=0.004) and serological response (OR=10.129; CI=2.440-42.044; p<0.001). Rs8099917 TT was predictive only of virological response (OR=3.746, CI=1.235-11.355; p=0.020). The E genotype was a negative predictive factor of virological response (OR=0.057; CI=0.014-0.238; p<0.001). IL28-B polymorphisms are related to different response in the treatment of CHB HBeAg-negative with PEG-IFN, and the E genotype is a novel negative predictive factor.

摘要

白细胞介素 28-B 多态性与丙型肝炎治疗中的干扰素反应有关,但在慢性乙型肝炎(CHB)治疗中的作用仍知之甚少。我们旨在研究白细胞介素 28-B 多态性在 CHB 患者接受聚乙二醇干扰素(PEG-IFN)治疗中的作用。我们回顾性分析了 190 例慢性乙型肝炎 e 抗原(HBeAg)阴性、基因型 A(22%)、B(12%)、C(10%)、D(33%)、E(20%)的患者,接受 PEG-IFN alfa-2a 治疗 48 周;根据病毒学、血清学和生化学应答情况,对白细胞介素 28-B 多态性 rs12979860、rs8099917 和 rs12980275 进行基因型分析。在 2 年的随访中,12 例(6.3%)患者 HBsAg 转阴并出现血清学转换,40 例(21%)患者病毒载量转阴,104 例(54.7%)患者出现生化学应答。我们发现 rs12979860 CC 基因型在不同种族之间的分布存在差异(p=0.013)。rs12979860 CC 基因型与血清学和病毒学应答显著相关(p<0.001);rs8099917 TT 和 rs12980275 AA 基因型与病毒学应答关系最为密切(p<0.001)。多因素 logistic 分析显示 rs12979860 CC 可预测病毒学应答(OR=4.290;95%CI=1.589-11.580,p=0.004)和血清学应答(OR=10.129;95%CI=2.440-42.044;p<0.001)。rs8099917 TT 仅可预测病毒学应答(OR=3.746,95%CI=1.235-11.355;p=0.020)。E 基因型是病毒学应答的阴性预测因子(OR=0.057;95%CI=0.014-0.238;p<0.001)。白细胞介素 28-B 多态性与 CHB HBeAg 阴性患者接受 PEG-IFN 治疗的不同应答有关,E 基因型是新的阴性预测因子。

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