Medical University of Vienna, Internal Medicine III, Department of Gastroenterology and Hepatology, Austria.
J Hepatol. 2011 May;54(5):866-71. doi: 10.1016/j.jhep.2010.08.024. Epub 2011 Jan 14.
BACKGROUND & AIMS: Polymorphisms of the IL28B gene (rs12979860 and rs8099917) are associated with high sustained virological response (SVR) rates in HCV genotype 1 patients. This study analyzes the impact of these IL28B polymorphisms on early treatment response (weeks 2 and 4) and SVR in HCV genotype 3 patients.
rs12979860 and rs8099917 were analyzed by the Step-OnePlus Real-time PCR system in 71 out of 72 Caucasian HCV genotype 3 patients participating, at our center, in a randomized study comparing 400mg with 800 mg ribavirin/day. HCV RNA was determined at weeks 2 and 4 of 180 μg/week peginterferon alfa-2a/ribavirin treatment. Sixty-nine patients completed the treatment and follow-up.
rs12979860 genotyping revealed that 27 (37.5%) patients had C/C, 39 (54.2%) T/C, and 5 (6.9%) T/T. Thirteen patients (18.1%) became HCV RNA negative at week 2 and an additional 30 (41.7%) at week 4 (rapid virologic response; RVR); thus a total of 43 had a RVR (C/C: 77.8%; T/C or T/T: 50.0%). Irrespective of the ribavirin dose, the viral load decline was larger than in those with the T allele (T/C or T/T) (week 2: 4.46; [0.36-6.02] median; [range] vs. 3.50; [0.14-5.62]; log IU HCV-RNA/ml; p<0.001; week 4: 4.97; [1.21-6.20] vs. 4.49; [1.16-6.23]; p=0.003). Despite the faster initial viral response in C/C carriers, SVR rates were not different compared to T-allele carriers. Results of the SNP in the rs8099917 region were similar.
IL28B polymorphisms modulate early virologic response to peginterferon/ribavirin treatment. In contrast to HCV genotype 1 patients, no effect on SVR rates was observed in genotype 3 patients. The clinical relevance of an earlier viral decline in C/C patients needs to be determined.
IL28B 基因（rs12979860 和 rs8099917）的多态性与 HCV 基因型 1 患者的高持续病毒学应答（SVR）率相关。本研究分析了这些 IL28B 多态性对 HCV 基因型 3 患者早期治疗应答（第 2 周和第 4 周）和 SVR 的影响。
72 例高加索 HCV 基因型 3 患者参与了我们中心的一项随机研究，比较了 400mg 和 800mg 利巴韦林/天的疗效，其中 71 例采用 Step-OnePlus 实时 PCR 系统分析 rs12979860 和 rs8099917。180μg/周聚乙二醇干扰素 alfa-2a/利巴韦林治疗的第 2 周和第 4 周测定 HCV RNA。69 例患者完成了治疗和随访。
rs12979860 基因分型显示 27 例（37.5%）患者为 C/C，39 例（54.2%）为 T/C，5 例（6.9%）为 T/T。13 例（18.1%）患者在第 2 周 HCV RNA 转阴，另有 30 例（41.7%）在第 4 周（快速病毒学应答；RVR）；因此共有 43 例获得 RVR（C/C：77.8%；T/C 或 T/T：50.0%）。无论利巴韦林剂量如何，携带 T 等位基因（T/C 或 T/T）的患者病毒载量下降幅度均大于携带 C 等位基因的患者（第 2 周：4.46；[0.36-6.02]中位数；[范围]vs. 3.50；[0.14-5.62]；log IU HCV-RNA/ml；p<0.001；第 4 周：4.97；[1.21-6.20]vs. 4.49；[1.16-6.23]；p=0.003）。尽管 C/C 携带者的初始病毒应答更快，但 SVR 率与 T 等位基因携带者无差异。rs8099917 区 SNP 的结果相似。
IL28B 多态性调节聚乙二醇干扰素/利巴韦林治疗的早期病毒学应答。与 HCV 基因型 1 患者不同，基因型 3 患者的 SVR 率无影响。需要确定 C/C 患者病毒早期下降的临床意义。
