Ishiguro Haruya, Abe Hiroshi, Seki Nobuyoshi, Sugita Tomonori, Aida Yuta, Itagaki Munenori, Sutoh Satoshi, Shimada Noritomo, Furihata Tomomi, Tsubota Akihito, Aizawa Yoshio
Haruya Ishiguro, Hiroshi Abe, Nobuyoshi Seki, Tomonori Sugita, Yuta Aida, Munenori Itagaki, Satoshi Sutoh, Yoshio Aizawa, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine Katsushika Medical Center, Tokyo 125-8506, Japan.
World J Gastroenterol. 2015 Apr 7;21(13):3904-11. doi: 10.3748/wjg.v21.i13.3904.
To evaluate interferon-λ3 (IFNL3) polymorphisms in response-guided pegylated interferon-α plus ribavirin (Peg-IFNα/RBV) therapy for genotype 2 (G2) chronic hepatitis C.
Between January 2006 and June 2012, a total of 180 patients with chronic infections of G2 hepatitis C virus (HCV) were treated with response-guided Peg-IFNα/RBV therapy. The treatment duration was 24 wk for patients who achieved rapid virologic response (RVR), and 36 or 48 wk for patients who did not. Then, the impact of the IFNL3 single nucleotide polymorphism genotype (TT/non-TT at rs8099917) on treatment outcomes was evaluated in the 180 patients, and between patients infected with either HCV sub-genotype 2a or 2b.
Of the 180 patients evaluated, 111 achieved RVR, while the remaining 69 patients did not. In RVR patients, the sustained virologic response (SVR) rate was 96.4%, and the IFNL3 genotype did not influence the SVR rate (96.6% vs 95.8% in IFNL3 genotype TT vs non-TT). However, in non-RVR patients, the SVR rate decreased to 72.5% (P < 0.0001), and this rate was significantly different between the IFNL3 genotype TT and non-TT groups (80.0% vs 42.9%, P = 0.0146). Multivariate regression analysis in non-RVR patients identified the IFNL3 genotype TT as the only baseline-significant factor associated with SVR (OR = 5.39, 95%CI: 1.29-22.62; P = 0.0189). In analysis according to HCV sub-genotype, no significant difference in the SVR rate was found between HCV sub-genotypes 2a and 2b.
In response-guided Peg-IFNα/RBV combination therapy for chronically HCV G2-infected patients, the impact of the IFNL3 genotype on SVR was limited to non-RVR patients.
评估干扰素-λ3（IFNL3）基因多态性在基因2型（G2）慢性丙型肝炎患者接受基于应答指导的聚乙二醇化干扰素-α联合利巴韦林（Peg-IFNα/RBV）治疗中的作用。
2006年1月至2012年6月期间，共180例G2型丙型肝炎病毒（HCV）慢性感染患者接受基于应答指导的Peg-IFNα/RBV治疗。达到快速病毒学应答（RVR）的患者治疗疗程为24周，未达到RVR的患者治疗疗程为36或48周。然后，在这180例患者以及感染HCV 2a或2b亚型的患者中，评估IFNL3单核苷酸多态性基因型（rs8099917位点的TT/非TT）对治疗结局的影响。
在评估的180例患者中，111例达到RVR，其余69例未达到。在RVR患者中，持续病毒学应答（SVR）率为96.4%，IFNL3基因型不影响SVR率（IFNL3基因型TT组与非TT组的SVR率分别为96.6%和95.8%）。然而，在非RVR患者中，SVR率降至72.5%（P<0.0001），且IFNL3基因型TT组与非TT组之间的SVR率存在显著差异（80.0%对42.9%，P = 0.0146）。非RVR患者的多因素回归分析确定IFNL3基因型TT是与SVR相关的唯一基线显著因素（OR = 5.39，95%CI：1.29 - 22.62；P = 0.0189）。根据HCV亚型分析，HCV 2a和2b亚型之间的SVR率未发现显著差异。
在基于应答指导的Peg-IFNα/RBV联合治疗慢性HCV G2感染患者中，IFNL3基因型对SVR的影响仅限于非RVR患者。
