干扰素λ4基因多态性对慢性丙型肝炎患者接受特拉匹韦、聚乙二醇干扰素和利巴韦林联合治疗疗效的影响。
Interferon lambda 4 polymorphism affects on outcome of telaprevir, pegylated interferon and ribavirin combination therapy for chronic hepatitis C.
作者信息
Nagaoki Yuko, Imamura Michio, Kawakami Yoshiiku, Kan Hiromi, Fujino Hatsue, Fukuhara Takayuki, Kobayashi Tomoki, Ono Atsushi, Nakahara Takashi, Naeshiro Noriaki, Urabe Ayako, Yokoyama Satoe, Miyaki Daisuke, Murakami Eisuke, Kawaoka Tomokazu, Tsuge Masataka, Hiramatsu Akira, Aikata Hiroshi, Takahashi Shoichi, Hayes C Nelson, Ochi Hidenori, Chayama Kazuaki
机构信息
Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
出版信息
Hepatol Res. 2014 Dec;44(14):E447-54. doi: 10.1111/hepr.12336. Epub 2014 May 6.
AIM
The predictive value of the recently identified interferon-λ (IFNL)4 polymorphism on the outcome of telaprevir (TVR), pegylated interferon (PEG IFN) plus ribavirin (RBV) combination therapy for chronic hepatitis C is unknown.
METHODS
We assessed predictive factors for sustained virological response (SVR) for TVR, PEG IFN plus RBV combination therapy in 283 genotype 1 chronic hepatitis C patients. IFNL4 polymorphism ss469415590 was analyzed by Invader assay.
RESULTS
SVR rates for patients with IFNL4 TT/TT genotype were significantly higher than for those with the IFNL4 TT/ΔG or ΔG/ΔG genotypes (93% and 59%, respectively, P < 0.0001). In a multivariate regression analysis, prior treatment history (treatment-naïve patients or patients who relapsed during prior treatment) (odds ratio [OR], 2.385; P = 0.028), rapid virological response (OR, 6.800; P < 0.0001) and ss469415590 TT/TT genotype (OR, 8.064; P < 0.0001) were identified as significant independent predictors for SVR. In patients with IFNL4 TT/ΔG or ΔG/ΔG genotypes, SVR rates for non-RVR patients were significantly lower than RVR patients (22% and 75%, respectively, P < 0.0001).
CONCLUSION
Analysis of IFNL4 polymorphism is a valuable predictor in patients receiving TVR triple therapy.
目的
最近发现的干扰素λ（IFNL）4基因多态性对慢性丙型肝炎患者接受特拉匹韦（TVR）、聚乙二醇干扰素（PEG IFN）联合利巴韦林（RBV）治疗结局的预测价值尚不清楚。
方法
我们评估了283例基因1型慢性丙型肝炎患者接受TVR、PEG IFN联合RBV治疗获得持续病毒学应答（SVR）的预测因素。采用Invader检测法分析IFNL4基因多态性ss469415590。
结果
IFNL4 TT/TT基因型患者的SVR率显著高于IFNL4 TT/ΔG或ΔG/ΔG基因型患者（分别为93%和59%，P<0.0001）。多因素回归分析显示，既往治疗史（初治患者或既往治疗中复发的患者）（比值比[OR]，2.385；P=0.028）、快速病毒学应答（OR，6.800；P<0.0001）和ss469415590 TT/TT基因型（OR，8.064；P<0.0001）是SVR的显著独立预测因素。在IFNL4 TT/ΔG或ΔG/ΔG基因型患者中，非快速病毒学应答患者的SVR率显著低于快速病毒学应答患者（分别为22%和75%，P<0.0001）。
结论
IFNL4基因多态性分析对接受TVR三联疗法的患者是一个有价值的预测指标。
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