de Seixas Santos Nastri Ana Catharina, de Mello Malta Fernanda, Diniz Márcio Augusto, Yoshino Alessandra, Abe-Sandes Kiyoko, Dos Santos Sidney Emanuel Batista, de Castro Lyra André, Carrilho Flair José, Pinho João Renato Rebello
Department of Infectious and Parasitic Diseases, School of Medicine, University of São Paulo, São Paulo, Brazil.
Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil.
Arch Virol. 2016 Jun;161(6):1477-84. doi: 10.1007/s00705-016-2809-8. Epub 2016 Mar 14.
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and associated complications such as liver cirrhosis and hepatocellular carcinoma (HCC). Viral and host factors are known to be predictors for antiviral therapy. Host factors that are predictors of sustained viral response (SVR) were discovered by genome-wide association studies (GWAS), including single-nucleotide polymorphisms (SNPs) in or near the interferon lambda gene (rs8099917, rs12979860 and rs368234815). The aim of the present study was to verify the genotype frequencies of SNPs rs8099917, rs12979860 and rs368234815 and to evaluate the association between SNPs and the outcome of HCV infection, taking into account the population ancestry. In this study, there was an association of the three polymorphisms with both clinical outcome and response to treatment with PEG-IFN and RBV. The polymorphisms rs12979860 and rs368234815 were associated with increased sensitivity (97.7 %, 95 % CI 87.2-100, and 93.3 %, 95 % CI 81.3-98.3; respectively) and with a greater predictive value of a positive response to treatment. In multivariable analysis adjusted by gender, age and ancestry, the haplotype G/T/ΔG was related to non-response to treatment (OR = 21.09, 95 % CI 5.33-83.51; p < 0.001) and to a higher chance of developing chronic infection (OR = 5.46, 95 % CI 2.06-14.46; p = 0.001) when compared to the haplotype T/C/TT. These findings may help to adjust our treatment policies for HCV infection based on greater certainty in studies with populations with such genetic characteristics, as well as allowing us to get to know the genetic profile of our population for these polymorphisms.
丙型肝炎病毒（HCV）感染是慢性肝病及相关并发症（如肝硬化和肝细胞癌（HCC））的主要病因。已知病毒和宿主因素可作为抗病毒治疗的预测指标。全基因组关联研究（GWAS）发现了一些可预测持续病毒学应答（SVR）的宿主因素，包括干扰素λ基因（rs8099917、rs12979860和rs368234815）内部或附近的单核苷酸多态性（SNP）。本研究的目的是验证SNP rs8099917、rs12979860和rs368234815的基因型频率，并考虑人群血统来评估SNP与HCV感染结局之间的关联。在本研究中，这三种多态性与临床结局以及聚乙二醇干扰素（PEG-IFN）和利巴韦林（RBV）治疗反应均存在关联。多态性rs12979860和rs368234815与敏感性增加相关（分别为97.7%，95%置信区间87.2 - 100，以及93.3%，95%置信区间81.3 - 98.3），并且对治疗阳性反应具有更高的预测价值。在按性别、年龄和血统进行校正的多变量分析中，与单倍型T/C/TT相比，单倍型G/T/ΔG与治疗无反应相关（比值比（OR）= 21.09，95%置信区间5.33 - 83.51；p < 0.001），且发生慢性感染的几率更高（OR = 5.46，95%置信区间2.06 - 14.46；p = 0.001）。这些发现可能有助于根据对具有此类遗传特征人群的研究中更高的确定性来调整我们针对HCV感染的治疗策略，同时也使我们能够了解我们人群中这些多态性的基因概况。
