聚乙二醇干扰素-α联合利巴韦林诱导的丙型肝炎病毒清除：一项西班牙药物遗传学多中心研究。

PEG-Interferon-α ribavirin-induced HCV viral clearance: a pharmacogenetic multicenter Spanish study.

作者信息

Milara Javier, Outeda-Macias Maria, Aumente-Rubio M Dolores, Más-Serrano Patricio, Aldaz Azucena, Calvo M Victoria, García-Simón M Sergia, Martin-Barbero Marisa, Padullés-Zamora Núria, Schoenenberger Juan Antonio, Saavedra-Aldrich Marianne, Tévar-Alfonso Enrique, Saval Ana, Pastor-Clerigues Alfonso, García Marta, Margusino-Framiñan Luis, Montero-Alvarez Jose Luis, Merino Esperanza, Herrero Jose Ignacio, Beunza Mónica, Conesa-Zamora Pablo, Gimenez-Manzorro Alvaro, Comas-Sugrañes Dolors, Cano-Marron Manuel, Jiménez-Mutiloa Elena, Díaz-Ruíz Pilar, Cortijo Julio

机构信息

Servicio de Farmacia del Hospital General Universitario de Valencia..

Servicio de Farmacia Complejo Hospitalario Universitario A Coruña..

出版信息

Farm Hosp. 2015 Jan 1;39(1):29-43. doi: 10.7399/fh.2015.39.1.8547.

DOI:10.7399/fh.2015.39.1.8547

PMID:25680433

Abstract

OBJECTIVE

Dual PEGylated interferon-α (PEG-IFN) and ribavirin therapy has been the main hepatitis C virus (HCV) treatment of the last decade. Current direct-acting antiviral agents have improved the outcome of therapy but also have increased the cost and management complexity of treatment. The current study analyzes host genetics, viral and clinical predictors of sustained viral response (SVR) to dual PEG-IFN and ribavirin therapy in a representative Spanish population.

METHODS

Observational prospective multicentre pharmacogenetic cohort study conducted in 12 different hospitals of 12 different Spanish regions. A total of 98 patients with SVR and 106 with non-SVR in response to PEG-IFN and ribavirin therapy were included. 33 single nucleotide polymorphisms located in 24 different genes related with inflammatory, immune and virus response were selected. Clinical and viral data were also analyzed as candidate of SVR predictors.

RESULTS

IL-28B (rs12979860, rs7248668, rs8105790, rs8099917) and TNFRSF1B (rs1061622) genotypes, as well as TNFRSF1B/IL-10/TNFα (-308) non-TTG and TNFRSF1B/IL- 10/IL-4 non-TTC haplotypes together with lower age, lower basal HCV RNA load, higher basal serum LDL cholesterol values, VHC genotypes 2 and 3 and basal low grade fibrosis 0-2 were associated with a SVR in the univariate analysis. Independent predictors of SVR in the multivariate analysis were IL-28B rs12979860 CC, TNFRSF1B/IL-10/IL-4 non-TTC along with low baseline HCV RNA load and HCV genotypes 2 and 3.

CONCLUSIONS

IL-28B rs12979860 CC, TNFRSF1B/ IL-10/ IL-4 non-TTC haplotype, low baseline HCV RNA load and HCV genotypes 2 and 3 may help to predict successful outcome to PEG-IFN/ribavirin therapy in Spanish population.

摘要

目的

聚乙二醇化干扰素-α（PEG-IFN）联合利巴韦林疗法在过去十年一直是丙型肝炎病毒（HCV）的主要治疗方法。目前的直接抗病毒药物改善了治疗效果，但也增加了治疗成本和管理复杂性。本研究分析了西班牙一个具有代表性人群中，宿主遗传学、病毒学及临床因素对PEG-IFN联合利巴韦林治疗持续病毒学应答（SVR）的预测作用。

方法

在西班牙12个不同地区的12家不同医院开展观察性前瞻性多中心药物遗传学队列研究。纳入98例对PEG-IFN联合利巴韦林治疗产生SVR的患者和106例未产生SVR的患者。选择了位于24个与炎症、免疫和病毒反应相关不同基因中的33个单核苷酸多态性。临床和病毒学数据也作为SVR预测因素的候选指标进行分析。

结果

单因素分析中，IL-28B（rs12979860、rs7248668、rs8105790、rs8099917）和TNFRSF1B（rs1061622）基因型，以及TNFRSF1B/IL-10/TNFα（-308）非TTG和TNFRSF1B/IL-10/IL-4非TTC单倍型，与年龄较小、基础HCV RNA载量较低、基础血清低密度脂蛋白胆固醇值较高、VHC基因型2和3以及基础低级别纤维化0-2相关，均与SVR有关。多因素分析中，SVR的独立预测因素为IL-28B rs12979860 CC、TNFRSF1B/IL-10/IL-4非TTC，以及低基线HCV RNA载量和HCV基因型2和3。