Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
J Med Virol. 2014 Nov;86(11):1877-85. doi: 10.1002/jmv.24037. Epub 2014 Aug 7.
The influence of genetic variation at the interleukin-28B (IL28B) locus on the natural course of hepatitis C virus (HCV) infection has not been fully investigated. The goal of this study was to examine whether an IL28B polymorphism (rs8099917) is associated with natural clearance of HCV and with disease parameters of HCV infection in an HCV hyperendemic area of Japan. The patients were 502 anti-HCV antibody-positive residents who participated in liver disease screening program from 2002 to 2004. Patients who underwent interferon-based therapy or had hepatocellular carcinoma were excluded. Of these patients, 149 were negative for HCV RNA (prior infection) and 353 were positive for HCV RNA or HCV core antigen (HCV carriers). In multivariate analysis, the IL28B TT genotype was a predictor for prior HCV infection. In addition, nine of the patients with prior HCV infection were positive for anti-HCV antibody with positive for HCV core antigen or HCV RNA before 2001, and these nine patients all had the IL28B TT genotype. Furthermore, the IL28B TT genotype was associated independently with higher HCV core antigen levels in HCV carriers. In contrast, the IL28B genotype did not affect the biochemical markers, such as alanine aminotransferase, hepatic fibrosis markers, and α-fetoprotein, and the degree of hepatic fibrosis assessed by transient elastography in HCV carriers. We concluded that IL28B polymorphism (TT genotype) is associated with spontaneous clearance of HCV and conversely with high viral loads in HCV carriers. In contrast, the IL28B genotype does not affect disease progression such as hepatic fibrosis.
白细胞介素 28B（IL28B）基因座的遗传变异对丙型肝炎病毒（HCV）感染的自然病程的影响尚未得到充分研究。本研究旨在探讨 IL28B 多态性（rs8099917）是否与日本 HCV 高流行地区 HCV 的自然清除以及 HCV 感染的疾病参数相关。这些患者是 2002 年至 2004 年期间参加肝脏疾病筛查计划的 502 名抗 HCV 抗体阳性居民。排除接受干扰素治疗或患有肝细胞癌的患者。这些患者中，149 例 HCV RNA 阴性（既往感染），353 例 HCV RNA 或 HCV 核心抗原阳性（HCV 携带者）。多变量分析显示，IL28B TT 基因型是既往 HCV 感染的预测因素。此外，9 例既往 HCV 感染者在 2001 年之前 HCV 核心抗原或 HCV RNA 阳性时抗 HCV 抗体阳性，且这 9 例患者均为 IL28B TT 基因型。此外，IL28B TT 基因型与 HCV 携带者的 HCV 核心抗原水平升高独立相关。相反，IL28B 基因型不影响 HCV 携带者的生化标志物，如丙氨酸氨基转移酶、肝纤维化标志物和甲胎蛋白，以及瞬时弹性成像评估的肝纤维化程度。我们得出结论，IL28B 多态性（TT 基因型）与 HCV 的自发清除相关，而与 HCV 携带者的高病毒载量相关。相反，IL28B 基因型不影响疾病进展，如肝纤维化。
