Infectious Diseases and Microbiology Unit, Hospital Universitario de Valme, Seville, Spain.
Curr Opin HIV AIDS. 2011 Nov;6(6):491-500. doi: 10.1097/COH.0b013e32834bca2d.
To update the information on genetic markers influencing the outcome of hepatitis C virus (HCV) infection.
Single-nucleotide polymorphisms (SNPs) in the region of the IL28B gene on chromosome 19, coding for the interferon (IFN)-λ3, are involved in HCV spontaneous and treatment-induced clearance, and may have an influence on liver fibrosis and inflammation in chronic carriers. The rs12979860 SNP has been recommended as single diagnostic genotype. IL28B variations are strongly associated with response to pegylated-IFN plus ribavirin (Peg-IFN/RBV) in patients with chronic infection by HCV genotype 1 or 4. Thus, the rs12979860 CC genotype is associated with a two-fold increase in the sustained virological response (SVR) rate in this setting. SVR is less influenced by IL28B variants in HCV genotype 2 or 3 carriers. The rs12979860 CC genotype frequencies vary among diverse genetic ancestor groups, explaining partly the differences in SVR among them. The underlying mechanisms are unclear, but it may involve the expression of IFN-stimulated genes in the liver. Inosine triphosphatase genotype is predictive of RBV-induced anemia, but its clinical usefulness is less straightforward than that of IL28B SNPs.
IL28B genotyping can aid in Peg-IFN/RBV clinical decision-making, and it may be useful in the selection of candidates for triple therapy with Peg-IFN/RBV plus direct-acting antiviral drugs.
更新影响丙型肝炎病毒（HCV）感染结局的遗传标志物的信息。
位于染色体 19 上的 IL28B 基因区域的单核苷酸多态性（SNP），编码干扰素（IFN）-λ3，与 HCV 自发性和治疗诱导清除有关，并且可能对慢性携带者的肝纤维化和炎症有影响。rs12979860 SNP 被推荐为单一诊断基因型。IL28B 变异与慢性 HCV 基因型 1 或 4 感染者对聚乙二醇干扰素加利巴韦林（Peg-IFN/RBV）的反应强烈相关。因此，在这种情况下，rs12979860 CC 基因型与持续病毒学应答（SVR）率增加两倍相关。IL28B 变异对 HCV 基因型 2 或 3 携带者的 SVR 影响较小。rs12979860 CC 基因型频率在不同遗传祖先群体中存在差异，部分解释了它们之间 SVR 的差异。潜在机制尚不清楚，但可能涉及肝脏中 IFN 刺激基因的表达。肌苷三磷酸酶基因型可预测 RBV 诱导的贫血，但与 IL28B SNPs 相比，其临床应用不那么直接。
IL28B 基因分型有助于 Peg-IFN/RBV 的临床决策，并且可能对 Peg-IFN/RBV 加直接作用抗病毒药物三联疗法的候选者的选择有用。
