An IL28B Polymorphism Determines Treatment Response of Hepatitis C Virus Genotype 2 or 3 Patients Who Do Not Achieve a Rapid Virologic Response
An IL28B Polymorphism Determines Treatment Response of Hepatitis C Virus Genotype 2 or 3 Patients Who Do Not Achieve a Rapid Virologic Response
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DOI：
10.1053/j.gastro.2010.05.079
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发表时间：
2010-09-01
期刊：
影响因子：
29.4
通讯作者：
Mchutchison, John G.
中科院分区：
文献类型：
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作者：
Mangia, Alessandra;Thompson, Alexander J.;Mchutchison, John G.
背景与目的：19号染色体上白细胞介素（IL）-28 B基因区域的多态性与聚乙二醇干扰素-α诱导的基因型1型丙型肝炎病毒（HCV）清除相关;尚无基因型2或3型HCV患者的数据。我们评估了IL-28 B多态性对聚乙二醇干扰素和利巴韦林治疗反应的影响，在一个特征良好的基因型2/3患者队列中。方法：分析268例患者的DNA（高加索人：基因型2，213;基因型3，55）。患者被随机分配到接受标准持续时间（24周; n = 68）或可变持续时间的治疗组。接受不同持续时间（VD）治疗且有快速病毒学应答（RVR）的患者接受12周治疗（VD 12; n = 122）;无RVR的患者接受24周治疗（VD 24; n = 78）。分析IL-28 B基因型（rs 12979860）与治疗应答的相关性。研究结果：IL-28 B基因型的频率如下：CC，37%; CT，48%; TT，15%; 82%的CC基因型患者获得持续病毒学应答（SVR），而CT基因型为75%，TT基因型为58%（P = 0.0046）。IL-28 B基因型之间的差异在未能达到RVR的患者中最大（VD 24 SVR率：CC，87%; CT，67%; TT，29%; P = .0002）。在RVR患者中（61%），IL-28 B基因型与SVR无关（所有IL-28 B基因型>70%）。在多变量逻辑回归模型中，IL-28 B基因型预测SVR（比值比，1.76; 95%置信区间，1.16-2.7）。结论：IL-28 B多态性与基因型2/3 HCV感染但未达到RVR的患者的SVR相关。IL-28 B基因型分析可用于指导治疗。
BACKGROUND & AIMS: Polymorphisms in the region of the interleukin (IL)-28B gene on chromosome 19 have been associated with peginterferon-alfa-induced clearance of genotype 1 hepatitis C virus (HCV); there are no data for patients with genotype 2 or 3 HCV. We evaluated the effects of IL-28B polymorphisms on response to treatment with peginterferon and ribavirin in a well-characterized cohort of genotype 2/3 patients. METHODS: DNA was analyzed from 268 patients (Caucasian: genotype 2, 213; genotype 3, 55). Patients were randomly assigned to groups that received standard duration (24 wk; n = 68) or variable durations of therapy. Patients who received variable durations (VD) and had a rapid virologic response (RVR) were treated for 12 weeks (VD12; n = 122); those without an RVR were treated for 24 weeks (VD24; n = 78). IL-28B genotypes (rs12979860) were analyzed for association with treatment response. RESULTS: The frequencies of the IL-28B genotypes were as follows: CC, 37%; CT, 48%; and TT, 15%; 82% of patients with the CC genotype achieved a sustained virologic response (SVR), compared with 75% with the CT and 58% with the TT genotypes (P = .0046). Differences between IL-28B genotypes were greatest among patients who failed to attain RVR (VD24 SVR rates: CC, 87%; CT, 67%; and TT, 29%; P = .0002). Among patients with RVRs (61%), the IL-28B genotype was not associated with SVR (>70% for all IL-28B genotypes). In a multivariable logistic regression model, IL-28B genotype predicted SVR (odds ratio, 1.76; 95% confidence interval, 1.16-2.7). CONCLUSIONS: An IL-28B polymorphism was associated with an SVR in patients infected with genotype 2/3 HCV who did not achieve a RVR. Analysis of IL-28B genotype might be used to guide treatment for these patients.