Wu Ruihong, Chi Xiumei, Wang Xiaomei, Sun Haibo, Lv Juan, Gao Xiuzhu, Yu Ge, Kong Fei, Xu Hongqin, Hua Rui, Jiang Jing, Sun Bing, Zhong Jin, Pan Yu, Niu Junqi
Department of Hepatology, First Hospital of Jilin University, 71 Xin Min Street, Changchun, Jilin Province 130021, China.
Department of Clinical Epidemiology, First Hospital of Jilin University, 71 Xin Min Street, Changchun, Jilin Province 130021, China.
Infect Genet Evol. 2016 Apr;39:132-140. doi: 10.1016/j.meegid.2016.01.020. Epub 2016 Jan 26.
Recently, the dinucleotide variant ss469415590 (TT/ΔG) in a novel gene, interferon lambda 4 (IFNL4), was identified as a stronger predictor of hepatitis C virus (HCV) clearance in individuals of African ancestry compared with rs12979860. We aimed to determine whether this variant contributes to treatment decisions in a Chinese population. A total of 447 chronic hepatitis C (CHC) patients (including 328 treated with interferon alpha-2b and ribavirin), 129 individuals who had spontaneously cleared HCV (SHC), and 169 healthy controls were retrospectively investigated. ss469415590 genotyping was performed using a mass spectrometry method (SEQUENOM). A higher proportion of SHC individuals carried the TT/TT genotype compared with CHC patients (95.3% vs. 88.8%, P=0.027). In patients with HCV genotype 1b, the ss469415590 variant was independently associated with sustained virologic response (SVR) (odds ratio [OR]=3.247, 95% confidence interval [CI]=1.038-10.159, P=0.043) and on-treatment virological responses, including rapid (RVR), complete early (cEVR), early (EVR), and end-of-treatment (ETVR), with a minimal OR of 3.73. Especially for patients with high viral load (≥4×10(5) IU/ml), ΔG allele carriers had a lower chance of achieving SVR compared with those carrying the TT/TT genotype (7.1% vs. 36.0%, P=0.034, OR [95% CI]=7.24 [1.02-318.45], negative predictive value=92.9%). In patients with HCV genotype 2a, no significant association between the ss154949590 variant and the virological response was identified (P>0.05). Additionally, we found that ss154949590 was in complete linkage disequilibrium with rs12979860. In conclusion, the IFNL4 ss154949590 TT/TT genotype favors spontaneous clearance of HCV. This same variant is associated with treatment-induced clearance in patients with genotype 1b, but not 2a. ss469415590 (or rs12979860) genotyping should be considered for patients with HCV genotype 1b and high viral load when making a choice between standard dual therapy and an IFN-free direct-acting antiviral regimen.
最近，一种新基因干扰素λ4（IFNL4）中的二核苷酸变异体ss469415590（TT/ΔG）被确定为与rs12979860相比，在非洲裔个体中丙型肝炎病毒（HCV）清除的更强预测指标。我们旨在确定该变异体是否对中国人群的治疗决策有影响。对447例慢性丙型肝炎（CHC）患者（包括328例接受α-2b干扰素和利巴韦林治疗的患者）、129例自发清除HCV（SHC）的个体以及169例健康对照进行了回顾性研究。采用质谱法（SEQUENOM）进行ss469415590基因分型。与CHC患者相比，SHC个体中携带TT/TT基因型的比例更高（95.3%对88.8%，P = 0.027）。在HCV基因1b型患者中，ss469415590变异体与持续病毒学应答（SVR）独立相关（优势比[OR]=3.247，95%置信区间[CI]=1.038 - 10.159，P = 0.043）以及治疗期间病毒学应答，包括快速病毒学应答（RVR）、完全早期病毒学应答（cEVR）、早期病毒学应答（EVR）和治疗结束时病毒学应答（ETVR），最小OR为3.73。特别是对于高病毒载量（≥4×l0⁵ IU/ml）的患者，与携带TT/TT基因型的患者相比，ΔG等位基因携带者实现SVR的机会更低（7.1%对36.0%，P = 0.034，OR[95%CI]=7.24[1.02 - 318.45]，阴性预测值=92.9%）。在HCV基因2a型患者中，未发现ss154949590变异体与病毒学应答之间存在显著关联（P>0.05）。此外，我们发现ss154949590与rs12979860完全连锁不平衡。总之，IFNL4 ss154949590 TT/TT基因型有利于HCV的自发清除。该相同变异体与基因1b型患者的治疗诱导清除相关，但与基因2a型患者无关。在HCV基因1b型且高病毒载量的患者中，在标准双联疗法和无干扰素直接抗病毒方案之间做出选择时，应考虑进行ss469415590（或rs12979860）基因分型。
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