Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
J Clin Virol. 2013 Apr;56(4):293-8. doi: 10.1016/j.jcv.2012.11.015.
Viral kinetics and host interleukin 28B (IL-28B) genotype determine treatment outcome in hepatitis C virus genotype 1 (HCV-1) infection.
We aimed to explore the interplay between interferon responsiveness at treatment week 4 and IL28B genotype in the achievement of a sustained virological response (SVR; undetectable HCV RNA 24-weeks after end-of-treatment).
Rs8099917 genotypes were determined in 528 HCV-1 patients with peginterferon/ribavirin. Interferon responsiveness were evaluated by the degree of week 4 viral reduction: <1 log(10) IU/mL, 1-2 logs(10) IU/mL, 2-3 logs(10) IU/mL, 3-4 logs(10) IU/mL and ≥4 logs(10) IU/mL reduction and/or undetectable HCV RNA, respectively.
The SVR rate was significantly higher in patients with great interferon responsiveness at week 4. A great interferon responsiveness was associated with younger age (P < 0.0001), lower body mass index (P = 0.0056), lower aspartate aminotransferase levels (P = 0.0009), higher hemogloblin concentration (P = 0.0033), higher platelet counts (P < 0.0001), male gender (P < 0.0001) and rs809997 TT-genotype (P < 0.0001). Comparing to non-TT genotype patients, TT genotype patients had a significantly higher SVR rate with moderate viral reduction (1-3 logs(10) IU/mL) at week 4 (58.9% vs. 18.2%, P < 0.001), and the SVR rate did not differ between TT/non-TT patients on the extreme ends (<1 or >3 log(10) IU/mL reduction) of week 4 interferon responsiveness. For non-TT genotype carriers who were with <3 logs(10) reduction, none (0/15) could have a complete early virological response and only 10.9% (7/64) of the patients had an SVR.
More profound interferon responsiveness is mandatory for HCV-1 patients with unfavorable IL-28B genotype.
病毒动力学和宿主白细胞介素 28B（IL-28B）基因型决定了丙型肝炎病毒基因型 1（HCV-1）感染的治疗结果。
我们旨在探讨治疗第 4 周干扰素反应性与 IL28B 基因型在实现持续病毒学应答（SVR；治疗结束后 24 周时 HCV RNA 不可检测）中的相互作用。
在 528 例接受聚乙二醇干扰素/利巴韦林治疗的 HCV-1 患者中确定了 rs8099917 基因型。通过第 4 周病毒减少程度评估干扰素反应性：<1 log（10）IU/mL、1-2 log（10）IU/mL、2-3 log（10）IU/mL、3-4 log（10）IU/mL 和≥4 log（10）IU/mL 减少和/或 HCV RNA 不可检测。
第 4 周干扰素反应性强的患者 SVR 率显著更高。强干扰素反应性与较年轻的年龄（P <0.0001）、较低的体重指数（P = 0.0056）、较低的天门冬氨酸转氨酶水平（P = 0.0009）、较高的血红蛋白浓度（P = 0.0033）、较高的血小板计数（P <0.0001）、男性（P <0.0001）和 rs809997 TT 基因型（P <0.0001）相关。与非 TT 基因型患者相比，TT 基因型患者第 4 周病毒中度减少（1-3 log（10）IU/mL）时 SVR 率显著更高（58.9% vs. 18.2%，P <0.001），而在第 4 周干扰素反应性的极端（<1 或>3 log（10）IU/mL 减少）时，TT/非 TT 患者的 SVR 率无差异。对于非 TT 基因型携带者，<3 log（10）减少的患者无一例（0/15）能够获得完全早期病毒学应答，仅有 10.9%（7/64）的患者获得 SVR。
对于 IL-28B 基因型不利的 HCV-1 患者，更强烈的干扰素反应性是必需的。
