Department of Infectious Diseases/Virology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
PLoS One. 2013 Nov 14;8(11):e80172. doi: 10.1371/journal.pone.0080172. eCollection 2013.
Recently, several genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) in proximity to IL28B predict spontaneous clearance of hepatitis C virus (HCV) infection as well as outcome following pegylated interferon and ribavirin therapy among genotype 1 infected patients. Additionally the presence of the otherwise favorable IL28B genetic variants in the context of HCV genotype 3 infection reportedly entail more pronounced liver fibrosis and steatosis. The present study aimed to evaluate the impact of IL28B SNP variability on liver stiffness as accessed by transient elastography.
Seven hundred and seventy-one Swedish HCV infected patients sequentially undergoing liver stiffness measurement by means of Fibroscan® in the context of a real-life trial had samples available for IL28B genotyping (rs12979860) and HCV genotyping.
CC(rs12979860) was more common among HCV genotype 2 or 3 infected treatment-naïve patients than among those infected with genotype 1 (P<0.0001). Additionally CC(rs12979860) among HCV genotype 3 infected patients was associated with higher liver stiffness values (P = 0.004), and higher AST to platelet ratio index (APRI; p = 0.02) as compared to carriers of the T allele. Among HCV genotype 1 infected patients, CC(rs12979860) was significantly associated with higher viral load (P = 0.001), with a similar non-significant trend noted among HCV genotype 3 infected patients.
This study confirms previous reports that the CC(rs12979860) SNP is associated with more pronounced liver pathology in patients chronically infected with HCV genotype 3 as compared to genotype 1, suggesting that IL28B genetic variants differently regulates the course of HCV infection across HCV genotypes.
最近，几项全基因组关联研究表明，IL28B 附近的单核苷酸多态性（SNPs）可预测丙型肝炎病毒（HCV）感染的自发性清除，以及基因型 1 感染患者接受聚乙二醇干扰素和利巴韦林治疗后的结果。此外，据报道，在 HCV 基因型 3 感染的情况下，存在其他有利的 IL28B 遗传变异会导致更明显的肝纤维化和脂肪变性。本研究旨在评估 IL28B SNP 变异性对瞬时弹性成像评估的肝硬度的影响。
771 例瑞典 HCV 感染患者在一项真实试验中连续接受 Fibroscan®进行肝硬度测量，这些患者有样本可用于 IL28B 基因分型（rs12979860）和 HCV 基因分型。
与基因型 1 感染患者相比，HCV 基因型 2 或 3 感染的未治疗患者中 CC(rs12979860)更为常见（P<0.0001）。此外，HCV 基因型 3 感染患者中 CC(rs12979860)与更高的肝硬度值（P = 0.004）和更高的天冬氨酸转氨酶与血小板比值指数（APRI；p = 0.02）相关，而 T 等位基因携带者则较低。在 HCV 基因型 1 感染患者中，CC(rs12979860)与更高的病毒载量显著相关（P = 0.001），而在 HCV 基因型 3 感染患者中也观察到类似的非显著趋势。
本研究证实了先前的报告，即 CC(rs12979860) SNP 与 HCV 基因型 3 感染患者相比，与更明显的肝病理学相关，提示 IL28B 遗传变异在不同程度上调节 HCV 感染在 HCV 基因型之间的进程。
