Unit of HIV/Hepatitis Coinfection, National Centre of Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid 28220, Spain.
J Viral Hepat. 2013 May;20(5):358-66. doi: 10.1111/jvh.12041. Epub 2012 Dec 20.
Due to the poor rate of response to hepatitis C virus (HCV) with pegylated interferon and ribavirin treatment in HCV/HIV coinfected patients, key factors for predicting failure would be useful. We performed a retrospective study on 291 patients on HCV treatment, who had early virological response (EVR) data. IL28B and IL28RA polymorphisms were performed using the GoldenGate(®) assay. Unfavourable genotypes at IL28B (rs12980275 AG/GG and rs8099917 GT/GG) and an unfavourable allele at IL28RA (rs10903035 G) were associated with early treatment failure. However, only the rs12980275 AG/GG genotype and rs10903035 G allele remained independently associated with early failure in the overall population (OR = 4.15 (95% CI = 1.64-10.54) and OR = 2.00 (95% CI = 1.19-3.36), respectively) as well as in GT1/4 patients (OR = 5.07 (95% CI = 1.81-14.22) and OR = 2.03 (95% CI = 1.13-3.66), respectively). Next, a decision tree showed early treatment failure increased from 37.1% to 65.5% when the unfavourable rs12980275 AG/GG and rs10903035 AG/GG genotypes and HCV-RNA≥ 500.000 IU/mL were taken into account in GT1/4 patients. In contrast, the failure rate decreased from 37.1% to 11.9% when the favourable rs12980275 AA and rs10903035 AA genotypes were detected. The percentage of patients correctly classified was 78.4%, and AUROC was 0.802 ± 0.028. Regarding GT3 patients, the presence of the GCGCA haplotype (all unfavourable alleles) was associated with early treatment failure, while no association was observed for the IL28B polymorphisms. In conclusion, the IL28RA polymorphism was associated with early treatment failure independently of the IL28B SNPs. The combination of IL28B and IL28RA polymorphisms might be a valuable tool for predicting early treatment failure before starting HCV treatment.
由于聚乙二醇干扰素和利巴韦林治疗丙型肝炎病毒（HCV）合并 HIV 感染患者的应答率较差，因此预测治疗失败的关键因素将是有用的。我们对 291 例接受 HCV 治疗的患者进行了回顾性研究，这些患者有早期病毒学应答（EVR）数据。IL28B 和 IL28RA 多态性使用 GoldenGate（®）assay 进行检测。IL28B 的不利基因型（rs12980275 AG/GG 和 rs8099917 GT/GG）和 IL28RA 的不利等位基因（rs10903035 G）与早期治疗失败相关。然而，仅 rs12980275 AG/GG 基因型和 rs10903035 G 等位基因在整个人群（OR=4.15（95%CI=1.64-10.54）和 OR=2.00（95%CI=1.19-3.36））以及 GT1/4 患者（OR=5.07（95%CI=1.81-14.22）和 OR=2.03（95%CI=1.13-3.66））中与早期失败独立相关。接下来，决策树显示，当 GT1/4 患者同时存在不利的 rs12980275 AG/GG 和 rs10903035 AG/GG 基因型以及 HCV-RNA≥500.000 IU/mL 时，早期治疗失败率从 37.1%增加到 65.5%。相比之下，当检测到有利的 rs12980275 AA 和 rs10903035 AA 基因型时，失败率从 37.1%降低至 11.9%。患者正确分类的百分比为 78.4%，AUROC 为 0.802±0.028。关于 GT3 患者，GCGCA 单倍型（所有不利等位基因）的存在与早期治疗失败相关，而 IL28B 多态性则没有关联。总之，IL28RA 多态性与 IL28B SNPs 无关，与早期治疗失败相关。IL28B 和 IL28RA 多态性的组合可能是预测 HCV 治疗前早期治疗失败的有用工具。
