Unidad de Aparato Digestivo, Hospital Universitario San Cecilio, Granada, Spain.
Am J Gastroenterol. 2011 Jul;106(7):1246-54. doi: 10.1038/ajg.2011.82. Epub 2011 Jun 14.
Viral factors are considered the best predictors of response to treatment for chronic hepatitis C (CHC), but genetic factors are known to have an important role in this respect. This paper investigates the relationships among the host genetic factors HLA and IL28B, viral factors, and the outcome of combination therapy.
A multicenter retrospective cohort of 428 previously untreated CHC patients was treated with pegylated interferon/ribavirin (pegIFN/RBV) for 48 weeks. In all, 378 (88%) of these patients were genotype 1 or 4, and 50 (12%) were genotype 2 or 3.
Multivariate logistic regression showed the rs12979860 CC genotype (adjusted odds ratio (aOR)=4.3, 95% confidence interval (95% CI): 2.6-7), the HLA-DQB10301 allele (aOR=2.08, 95% CI: 1.2-3.5) and age, viral genotype, and viral load levels to be significantly associated with sustained virological response (SVR). When the variable rs12979860 was eliminated, the area under the receiver operating characteristic (ROC) curve (AUC) decreased significantly (0.76 vs. 0.69; P=0.03). AUC values derived from viral factors were lower than those corresponding to host genetic factors (0.67 vs. 0.72, respectively; P=0.04). The HLA-DQB10301 and A*0201 alleles were associated with rs12979860 CC genotype and SVR (P<0.0001).
The HLA-DQB10301 allele and IL28B genotype are factors that are associated independently with SVR. There is a synergism between the HLA-DQB10301 and HLA-A*0201 alleles with polymorphism rs12979860 CC, which increases the SVR rate. IL28B genotype is the best predictor of SVR.
病毒因素被认为是慢性丙型肝炎（CHC）治疗反应的最佳预测因子，但遗传因素在这方面也起着重要作用。本文研究了宿主遗传因素 HLA 和 IL28B、病毒因素与联合治疗结局之间的关系。
对 428 例未经治疗的 CHC 患者进行了多中心回顾性队列研究，这些患者接受聚乙二醇干扰素/利巴韦林（pegIFN/RBV）治疗 48 周。其中，378 例（88%）患者为基因型 1 或 4 型，50 例（12%）患者为基因型 2 或 3 型。
多变量逻辑回归显示，rs12979860 CC 基因型（调整优势比（aOR）=4.3，95%置信区间（95%CI）：2.6-7）、HLA-DQB10301 等位基因（aOR=2.08，95%CI：1.2-3.5）和年龄、病毒基因型和病毒载量水平与持续病毒学应答（SVR）显著相关。当排除变量 rs12979860 时，受试者工作特征（ROC）曲线下面积（AUC）显著降低（0.76 与 0.69；P=0.03）。来自病毒因素的 AUC 值低于对应宿主遗传因素的 AUC 值（分别为 0.67 与 0.72，P=0.04）。HLA-DQB10301 和 A*0201 等位基因与 rs12979860 CC 基因型和 SVR 相关（P<0.0001）。
HLA-DQB10301 等位基因和 IL28B 基因型是与 SVR 独立相关的因素。HLA-DQB10301 等位基因与 HLA-A*0201 等位基因与 rs12979860 CC 多态性的协同作用增加了 SVR 率。IL28B 基因型是 SVR 的最佳预测因子。
