Department of Internal Medicine III, Medical University, Vienna, Austria.
Hepatology. 2011 Nov;54(5):1518-26. doi: 10.1002/hep.24546.
The IL28B genotype is the most important pretreatment predictor of treatment outcome in patients with chronic hepatitis C. The impact of the rs12979860 genotype on relapse was retrospectively evaluated in genotype 1/4 patients who received response-guided therapy with peginterferon alpha-2a 180 μg/week plus ribavirin 1,000/1,200 mg/day in a large, randomized, multicenter study. Patients with a rapid virologic response (RVR: hepatitis C virus [HCV] RNA <50 IU/mL) at week 4 were treated for 24 weeks; those with a slow virologic response (no RVR but undetectable HCV RNA or ≥ 2-log(10) decrease at week 12) were randomized to 48 (group A) or 72 weeks of treatment (group B). Relapse rates were compared by rs12979860 genotype (C/C versus combined T/C or T/T [T/]) in patients with confirmed end-of-treatment response and known end-of-follow-up status (sustained virologic response [SVR] or relapse). The rs12979860 genotype was determined for 340/551 study participants. In patients with RVR and C/C or T/ genotype, relapse rates were similar (10.7% versus 15.2%). In patients randomized to groups A and B, relapse rates were similar in patients with C/C genotype randomized to group A (26.9%) and group B (20.0%). In contrast, relapse rates in T/* patients differed markedly between groups A and B, overall (42.9% and 18.8%; P < 0.025, respectively) and in those with low (<400,000 IU/mL: 37.5% versus 18.8%) and high (≥ 400,000 IU/mL: 45.0% versus 18.8%) baseline viral loads.
The results suggest that the benefits of extended therapy are restricted to patients with a T allele. Relapse rates are highest in patients with T/* genotype and are markedly higher in slow responders treated for 48 weeks compared with 72 weeks.
IL28B 基因型是慢性丙型肝炎患者治疗结果最重要的预处理预测因子。在一项大型、随机、多中心研究中，对接受聚乙二醇干扰素 alpha-2a 180 μg/周联合利巴韦林 1000/1200 mg/天应答指导治疗的基因型 1/4 患者，回顾性评估 rs12979860 基因型对复发的影响。第 4 周快速病毒学应答（RVR：丙型肝炎病毒[HCV]RNA<50IU/mL）的患者接受 24 周治疗；那些应答缓慢（无 RVR 但第 12 周时 HCV RNA 不可检测或≥2-log（10）下降）的患者随机分为 48（A 组）或 72 周治疗（B 组）。在有明确治疗结束时应答和随访结束时状态（持续病毒学应答[SVR]或复发）的患者中，通过 rs12979860 基因型（C/C 与合并 T/C 或 T/T[T/*]）比较复发率。在 551 名研究参与者中，有 340 人确定了 rs12979860 基因型。在 RVR 和 C/C 或 T/*基因型的患者中，复发率相似（10.7%比 15.2%）。在随机分为 A 组和 B 组的患者中，C/C 基因型随机分至 A 组（26.9%）和 B 组（20.0%）的患者复发率相似。相反，T/*患者的复发率在 A 组和 B 组之间存在显著差异，总体而言（42.9%和 18.8%；分别为 P<0.025），低（<400,000IU/mL：37.5%比 18.8%）和高（≥400,000IU/mL：45.0%比 18.8%）基线病毒载量患者中也是如此。
结果表明，延长治疗的益处仅限于 T 等位基因患者。T/*基因型患者的复发率最高，与治疗 48 周相比，治疗 72 周的应答缓慢患者的复发率显著更高。
