The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa Department of Gastroenterology, Juntendo University School of Medicine, Bunkyoku, Japan.
Hepatol Res. 2012 Oct;42(10):958-65. doi: 10.1111/j.1872-034X.2012.01013.x. Epub 2012 Apr 26.
IL28B polymorphisms serve to predict response to pegylated interferon plus ribavirin therapy (PEG IFN/RBV) in Japanese patients with chronic hepatitis C (CHC) very reliably. However, the prediction by the IL28B polymorphism contradicted the virological response to PEG IFN/RBV in some patients. Here, we aimed to investigate the factors responsible for the discrepancy between the IL28B polymorphism prediction and virological responses.
CHC patients with genotype 1b and high viral load were enrolled in this study. In a case-control study, clinical and virological factors were analyzed for 130 patients with rs8099917 TT genotype and 96 patients with rs8099917 TG or GG genotype who were matched according to sex, age, hemoglobin level and platelet count.
Higher low-density lipoprotein (LDL) cholesterol, lower γ-glutamyltransferase and the percentage of wild-type phenotype at amino acids 70 and 91 were significantly associated with the rs8099917 TT genotype. Multivariate analysis showed that rs8099917 TG or GG genotype, older age and lower LDL cholesterol were independently associated with the non-virological responder (NVR) phenotype. In patients with rs8099917 TT genotype (predicted as virological responder [VR]), multivariate analysis showed that older age was independently associated with NVR. In patients with rs8099917 TG or GG genotype (predicted as NVR), multivariate analysis showed that younger age was independently associated with VR.
Patient age gave rise to the discrepancy between the prediction by IL28B polymorphism and the virological responses, suggesting that patients should be treated at a younger age.
IL28B 多态性可可靠地预测日本慢性丙型肝炎(CHC)患者对聚乙二醇干扰素加利巴韦林治疗(PEG IFN/RBV)的反应。然而,IL28B 多态性的预测与某些患者对 PEG IFN/RBV 的病毒学反应相矛盾。在此,我们旨在研究导致 IL28B 多态性预测与病毒学反应之间差异的因素。
本研究纳入基因型 1b 且病毒载量高的 CHC 患者。在病例对照研究中,对 130 例 rs8099917 TT 基因型和 96 例 rs8099917 TG 或 GG 基因型的患者进行临床和病毒学因素分析,这些患者根据性别、年龄、血红蛋白水平和血小板计数进行匹配。
较低的低密度脂蛋白(LDL)胆固醇、较低的γ-谷氨酰转移酶以及氨基酸 70 和 91 处野生型表型的百分比与 rs8099917 TT 基因型显著相关。多变量分析显示,rs8099917 TG 或 GG 基因型、年龄较大和 LDL 胆固醇较低与非病毒学应答者(NVR)表型独立相关。在 rs8099917 TT 基因型(预测为病毒学应答者[VR])的患者中,多变量分析显示年龄较大与 NVR 独立相关。在 rs8099917 TG 或 GG 基因型(预测为 NVR)的患者中,多变量分析显示年龄较小与 VR 独立相关。
患者年龄导致了 IL28B 多态性预测与病毒学反应之间的差异,这表明应在更年轻时对患者进行治疗。