Bokharaei-Salim Farah, Salehi-Vaziri Mostafa, Sadeghi Farzin, Esghaei Maryam, Monavari Seyed Hamidreza, Alavian Seyed Moayed, Fakhim Shahin, Keyvani Hossein
Department of Virology, Iran University of Medical Sciences, Tehran, IR Iran; HIV Laboratory of National Center, Deputy of Health, Iran University of Medical Sciences, Tehran, IR Iran.
Department of Arboviruses and Viral Hemorrhagic Fevers (National Ref Lab), Pasteur Institute of Iran, Tehran, IR Iran.
Hepat Mon. 2016 Apr 23;16(5):e35597. doi: 10.5812/hepatmon.35597. eCollection 2016 May.
The hepatitis C virus (HCV) infection has been identified as a leading cause of progressive liver diseases worldwide. Despite new treatment strategies, pegylated interferon alfa-2a (Peg-IFNα-2a), in combination with ribavirin (RBV), still represents the gold standard of therapy for hepatitis C in developing countries.
The aim of this study was to investigate the association of substitutions in the HCV subtype 1b (HCV-1b) core protein and the rs12979860 polymorphism in the interleukin 28B gene (IL28B) with the response to Peg-IFNα-2a/RBV combination therapy in Azerbaijani patients.
A total of fifty-one chronically HCV-1b-infected Azerbaijani patients were enrolled in this cross-sectional study from March 2010 to June 2015. After RNA extraction from pre-treatment plasma, the core region of the HCV genome was amplified using the nested reverse transcription (RT) polymerase chain reaction (PCR) method, followed by standard sequencing. In addition, genomic DNA was extracted from peripheral blood mononuclear cell (PBMC) specimens, and the rs12979860 single nucleotide polymorphism (SNP) was identified using a PCR-restriction fragment length polymorphism (PCR-RFLP) assay.
In this study, a significant association was observed between the non-responders and relapsers to antiviral therapy and substitutions in the HCV-1b core region at positions 43 (R43K, P = 0.047), 70 (R70Q, P < 0.001), 91 (M91L, P = 0.037), and 106 (S106N, P = 0.018). Concerning the IL28B polymorphism, the results showed that sustained virological response was significantly associated with homozygous CC patients (P = 0.009) as compared with other genotypes, while homozygous TT subjects were associated with HCV relapse after therapy (P = 0.006).
The data of the present study suggest that amino acid substitutions at position 43, 70, 91, and 106 in the HCV-1b core protein are correlated with the response to the Peg-IFNα-2a/RBV treatment in Azerbaijani patients with chronic hepatitis C. Moreover, host genetic polymorphisms, such as those of the IL28B locus, might be useful for predicting the responsiveness to Peg-IFNα-2a/RBV combination therapy against HCV.
丙型肝炎病毒（HCV）感染已被确认为全球范围内进展性肝病的主要病因。尽管有新的治疗策略，但聚乙二醇化干扰素α-2a（Peg-IFNα-2a）联合利巴韦林（RBV）在发展中国家仍是丙型肝炎治疗的金标准。
本研究旨在探讨阿塞拜疆患者中HCV 1b亚型（HCV-1b）核心蛋白的替代突变以及白细胞介素28B基因（IL28B）中的rs12979860多态性与对Peg-IFNα-2a/RBV联合治疗反应之间的关联。
2010年3月至2015年6月，共有51例慢性HCV-1b感染的阿塞拜疆患者纳入本横断面研究。从治疗前血浆中提取RNA后，使用巢式逆转录（RT）聚合酶链反应（PCR）方法扩增HCV基因组的核心区域，随后进行标准测序。此外，从外周血单个核细胞（PBMC）标本中提取基因组DNA，并使用PCR-限制性片段长度多态性（PCR-RFLP）分析鉴定rs12979860单核苷酸多态性（SNP）。
在本研究中，观察到抗病毒治疗无应答者和复发者与HCV-1b核心区域43位（R43K，P = 0.047）、70位（R70Q，P < 0.001）、91位（M91L，P = 0.037）和106位（S106N，P = 0.018）的替代突变之间存在显著关联。关于IL28B多态性，结果显示与其他基因型相比，持续病毒学应答与纯合CC患者显著相关（P = 0.009），而纯合TT受试者与治疗后HCV复发相关（P = 0.006）。
本研究数据表明，HCV-1b核心蛋白43、70、91和l06位的氨基酸替代突变与阿塞拜疆慢性丙型肝炎患者对Peg-IFNα-2a/RBV治疗的反应相关。此外，宿主基因多态性，如IL28B基因座的多态性，可能有助于预测对Peg-IFNα-2a/RBV联合治疗HCV的反应性。
