Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
J Clin Virol. 2014 Nov;61(3):423-9. doi: 10.1016/j.jcv.2014.08.020. Epub 2014 Sep 1.
The CXCL9, CXCL10 and CXCL11 (CXCL9-11) chemokines play a critical role in eradication of hepatitis C virus (HCV), although HCV-specific immunity often fails to eradicate the HCV, allowing the chronicity of hepatitis C.
To examine the association between CXCL9-11 polymorphisms and the sustained virological response (SVR) following hepatitis C virus (HCV) therapy with pegylated-interferon-alpha plus ribavirin in HIV/HCV-coinfected patients.
We performed a retrospective study in 176 naïve patients who started HCV treatment. The CXCL9 rs10336, CXCL10 rs3921 and CXCL11 rs4619915 polymorphisms were genotyped by GoldenGate(®) assay. Genetic data were analyzed under recessive inheritance model. The SVR was defined as undetectable HCV viremia through 24 weeks after the end of HCV treatment.
In the intention-to-treat analysis, the SVR rate was higher in HCV genotype 1/4 (GT1/4) patients carrying rs10336 TT (p=0.042), rs3921 GG (p=0.021), and rs4619915 AA (p=0.024) genotypes; and they had higher likelihood of achieving SVR (adjusted odds ratio (aOR)=3.26 (p=0.038), aOR=4.21 (p=0.019), and aOR=4.08 (p=0.022), respectively). For CXCL haplotype analysis (CXCL9/rs10336, CXCL10/rs3921, and CXCL11/rs4619915), the TGA haplotype (favorable alleles) had better odds of achieving SVR than the CCG haplotype (unfavorable alleles) in GT1/4patients (OR=2.69; p=0.003). No significant results were found in GT2/3 patients. Moreover, similar results were obtained in the on-treatment analysis.
The presence of homozygous for the minor allele of CXCL9 rs10336, CXCL10 rs3921 and CXCL11 rs4619915 was related to higher likelihoods of achieving the HCV clearance after pegIFNα/ribavirin therapy in HIV infected patients coinfected with HCV GT1/4.
趋化因子 CXCL9、CXCL10 和 CXCL11（CXCL9-11）在清除丙型肝炎病毒（HCV）方面发挥着关键作用，尽管 HCV 特异性免疫通常无法清除 HCV，导致丙型肝炎持续存在。
研究 CXCL9-11 多态性与 HIV/HCV 合并感染患者接受聚乙二醇干扰素-α加利巴韦林治疗 HCV 后持续病毒学应答（SVR）之间的关系。
我们对 176 名开始 HCV 治疗的初治患者进行了回顾性研究。通过 GoldenGate（®）assay 对 CXCL9 rs10336、CXCL10 rs3921 和 CXCL11 rs4619915 多态性进行基因分型。遗传数据在隐性遗传模型下进行分析。SVR 定义为 HCV 治疗结束后 24 周内 HCV 病毒载量不可检测。
在意向治疗分析中，携带 rs10336 TT（p=0.042）、rs3921 GG（p=0.021）和 rs4619915 AA（p=0.024）基因型的 HCV 基因型 1/4（GT1/4）患者的 SVR 率更高；他们更有可能达到 SVR（调整后的优势比（aOR）=3.26（p=0.038），aOR=4.21（p=0.019）和 aOR=4.08（p=0.022））。对于 CXCL 单倍型分析（CXCL9/rs10336、CXCL10/rs3921 和 CXCL11/rs4619915），在 GT1/4 患者中，TGA 单倍型（有利等位基因）比 CCG 单倍型（不利等位基因）更有可能达到 SVR（OR=2.69；p=0.003）。在 GT2/3 患者中未发现显著结果。此外，在治疗期间分析中也得到了类似的结果。
在 HIV 感染合并 HCV GT1/4 的患者中，携带 CXCL9 rs10336、CXCL10 rs3921 和 CXCL11 rs4619915 次要等位基因纯合的患者，在接受 pegIFNα/利巴韦林治疗后，更有可能实现 HCV 清除。
