Imran Muhammad, Manzoor Sobia, Ashraf Javed, Khalid Madiha, Tariq Muqddas, Khaliq Hafiza Madeha, Azam Sikandar
Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology (NUST), 44000 Islamabad, Pakistan.
Virol J. 2013 Oct 1;10:299. doi: 10.1186/1743-422X-10-299.
The current standard of care (SOC) for hepatitis C virus (HCV) infection is the combination of pegylated interferon (PEG-IFN), Ribavirin and protease inhibitor for HCV genotype 1. Nevertheless, this treatment is successful only in 70-80% of the patients. In addition, the treatment is not economical and is of immense physical burden for the subject. It has been established now, that virus-host interactions play a significant role in determining treatment outcomes. Therefore identifying biological markers that may predict the treatment response and hence treatment outcome would be useful. Both IFN and Ribavirin mainly act by modulating the immune system of the patient. Therefore, the treatment response is influenced by genetic variations of the human as well as the HCV genome. The goal of this review article is to summarize the impact of recent scientific advances in this area regarding the understanding of human and HCV genetic variations and their effect on treatment outcomes. Google scholar and PubMed have been used for literature research. Among the host factors, the most prominent associations are polymorphisms within the region of the interleukin 28B (IL28B) gene, but variations in other cytokine genes have also been linked with the treatment outcome. Among the viral factors, HCV genotypes are noteworthy. Moreover, for sustained virological responses (SVR), variations in core, p7, non-structural 2 (NS2), NS3 and NS5A genes are also important. However, all considered single nucleotide polymorphisms (SNPs) of IL28B and viral genotypes are the most important predictors for interferon based therapy of HCV infection.
目前丙型肝炎病毒(HCV)感染的标准治疗方案(SOC)是聚乙二醇化干扰素(PEG-IFN)、利巴韦林以及针对HCV 1型的蛋白酶抑制剂联合使用。然而,这种治疗仅在70%-80%的患者中取得成功。此外,该治疗不经济,且给患者带来巨大的身体负担。现已明确,病毒与宿主的相互作用在决定治疗结果方面起着重要作用。因此,识别可能预测治疗反应进而预测治疗结果的生物标志物将很有帮助。干扰素和利巴韦林主要通过调节患者的免疫系统发挥作用。因此,治疗反应受人类以及HCV基因组的基因变异影响。这篇综述文章的目的是总结该领域近期科学进展对理解人类和HCV基因变异及其对治疗结果的影响。已使用谷歌学术和PubMed进行文献研究。在宿主因素中,最显著的关联是白细胞介素28B(IL28B)基因区域内的多态性,但其他细胞因子基因的变异也与治疗结果有关。在病毒因素中,HCV基因型值得关注。此外,对于持续病毒学应答(SVR),核心、p7、非结构2(NS2)、NS3和NS5A基因的变异也很重要。然而,综合考虑,IL28B的单核苷酸多态性(SNP)和病毒基因型是基于干扰素治疗HCV感染最重要的预测指标。