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白细胞介素-28B基因多态性与抗HBe阳性慢性HBV感染患者对聚乙二醇化干扰素α-2a单药治疗反应的关系。

The relationship between IL-28B polymorphisms and the response to peginterferon alfa-2a monotherapy in anti-HBe-positive patients with chronic HBV infection.

作者信息

Domagalski K, Pawłowska M, Zaleśna A, Tyczyno M, Skorupa-Kłaput M, Tretyn A, Halota W

机构信息

Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, Toruń, Poland.

出版信息

Eur J Clin Microbiol Infect Dis. 2014 Nov;33(11):2025-33. doi: 10.1007/s10096-014-2172-1. Epub 2014 Jun 13.

DOI:10.1007/s10096-014-2172-1
PMID:24924923
Abstract

The impact of interleukin 28B (IL-28B) on the results of interferon (IFN)-based therapy in patients chronically infected with hepatitis B virus (HBV) is poorly understood. The aim of this study was to evaluate the relationship between IL-28B markers and the response to IFN monotherapy in Polish patients with anti-hepatitis B e (HBe)-positive chronic hepatitis B (CHB). We determined three single-nucleotide polymorphisms (SNPs) of IL-28B (rs12979860, rs12980275, and rs8099917) in 86 patients who were treated with pegylated interferon (PEG-IFN) for 48 weeks. The effectiveness of the therapy was evaluated based on the virological and biochemical response. The primary efficacy parameters were the HBV DNA viral load below 400 IU/ml and 2,000 IU/ml in combination with alanine aminotransferase (ALT) normalization (<40 IU/l), measured 24 weeks after the treatment. Viral load below 400 IU/ml or 2,000 IU/ml with ALT normalization was achieved by 37 % and 46 % of patients, respectively. It has been shown that the distribution of IL-28B genotypes in the dominant genetic model in patients with different therapeutic success differ significantly only for rs12979860. The IL-28B rs12979860 CC genotype was associated with lower treatment success [odds ratio (OR), 0.31; p = 0.025 and OR, 0.37; p = 0.044 for <400 IU/ml HBV DNA with <40 IU/l ALT, and <2,000 IU/ml HBV DNA with <40 IU/l ALT, respectively]. However, in the conditional logistic regression analysis adjusted by factors associated with combined response, rs12979860 was significantly associated only with <400 IU/ml HBV DNA with <40 IU/l ALT (OR, 0.24; p = 0.026). IL-28B polymorphisms have prognostic significance in assessing the treatment effectiveness based on the virological and biochemical response of patients with anti-HBe-positive CHB.

摘要

白细胞介素28B(IL-28B)对慢性感染乙型肝炎病毒(HBV)患者基于干扰素(IFN)治疗结果的影响尚不清楚。本研究旨在评估波兰抗乙型肝炎e抗原(HBe)阳性慢性乙型肝炎(CHB)患者中IL-28B标志物与干扰素单药治疗反应之间的关系。我们在86例接受聚乙二醇干扰素(PEG-IFN)治疗48周的患者中测定了IL-28B的三个单核苷酸多态性(SNP)(rs12979860、rs12980275和rs8099917)。基于病毒学和生化反应评估治疗效果。主要疗效参数为治疗24周后乙肝病毒(HBV)DNA病毒载量低于400 IU/ml和2000 IU/ml,同时丙氨酸氨基转移酶(ALT)恢复正常(<40 IU/l)。分别有37%和46%的患者实现了病毒载量低于400 IU/ml或2000 IU/ml且ALT恢复正常。结果显示,仅rs12979860在不同治疗成功率患者的显性遗传模型中,IL-28B基因型分布存在显著差异。IL-28B rs12979860 CC基因型与较低的治疗成功率相关[比值比(OR),0.31;p = 0.025,以及对于HBV DNA<400 IU/ml且ALT<40 IU/l和HBV DNA<2000 IU/ml且ALT<40 IU/l,OR分别为0.37;p = 0.044]。然而,在经与联合反应相关因素调整的条件逻辑回归分析中,rs12979860仅与HBV DNA<400 IU/ml且ALT<40 IU/l显著相关(OR,0.24;p = 0.026)。IL-28B多态性在基于抗HBe阳性CHB患者的病毒学和生化反应评估治疗效果方面具有预后意义。

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本文引用的文献

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2
IL28B genotype is not useful for predicting treatment outcome in Asian chronic hepatitis B patients treated with pegylated interferon-α.基因分型对聚乙二醇干扰素α治疗的亚洲慢性乙型肝炎患者的治疗结果预测没有帮助。
J Gastroenterol Hepatol. 2013 May;28(5):861-6. doi: 10.1111/jgh.12110.
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Randomised study comparing 48 and 96 weeks peginterferon α-2a therapy in genotype D HBeAg-negative chronic hepatitis B.
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The influence of anti-HBc status on the sustained virological response rate in HCV-infected patients treated with pegylated interferon alfa 2 and ribavirin.抗-HBc状态对接受聚乙二醇化干扰素α-2和利巴韦林治疗的丙型肝炎病毒感染患者持续病毒学应答率的影响。
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