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受体和供体的IL28B基因多态性共同影响肝移植后丙型肝炎病毒(HCV)复发时的干扰素治疗反应,但受体的IL28B单核苷酸多态性在干扰素诱导的HCV复制阻断中起主要作用。

IL28B polymorphisms of both recipient and donor cooperate to influence IFN treatment response in HCV recurrence after liver transplantation, but IL28B SNPs of the recipient play a major role in IFN-induced blocking of HCV replication.

作者信息

Barbera Floriana, Russelli Giovanna, Pipitone Loredana, Pietrosi Giada, Corsale Sveva, Vizzini Giovanni, Gridelli Bruno, Conaldi Pier Giulio

机构信息

Vita-Salute San Raffaele University, Milan, Italy; Regenerative Medicine and Biomedical Technologies Unit, ISMETT, Palermo, Italy.

Department of Diagnostic and Therapeutic Services, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Palermo, Italy.

出版信息

New Microbiol. 2015 Apr;38(2):201-10. Epub 2015 Apr 29.

Abstract

Single nucleotide polymorphisms (SNPs) of the IL28B locus are associated with a positive response to pegylated interferon-alpha and ribavirin (pegIFN-alpha/RBV) treatment of HCV-infected patients. This study evaluated the association between SNPs rs12980275, rs12979860 and rs8099917 and treatment outcome of HCV recurrent infection in HCV-positive patients who underwent liver transplant. We aimed to assess to what extent recipient and/or graft donor IL28B polymorphisms contribute to HCV clearance after transplantation influencing the response to the antiviral treatment. We found that the allele frequencies in donors were in agreement with the pattern expected in the European population. The frequency of favourable genotypes was significantly lower in recipients than in donors, reasonably because the recipients represented a group of patients affected by chronic Hepatitis C. Our study demonstrated that the positive outcome of the pegIFN-alpha/RBV treatment of HCV recurrence is associated with the co-presence of favourable genotypes of both donors and recipients. However, IL28B SNPs of the recipient seem to play a major role in this clinical setting. In particular, homozygosis of rs12979860 favourable genotype in recipients was associated with sustained virological response independently from the donor's genotype. Thus, identification of these SNPs may be useful to predict the response to IFN-based therapy of HCV recurrent infection in liver-transplanted patients.

摘要

白细胞介素28B(IL28B)基因座的单核苷酸多态性(SNP)与丙型肝炎病毒(HCV)感染患者接受聚乙二醇化干扰素-α和利巴韦林(pegIFN-α/RBV)治疗的阳性反应相关。本研究评估了SNP rs12980275、rs12979860和rs8099917与接受肝移植的HCV阳性患者HCV复发感染治疗结果之间的关联。我们旨在评估受体和/或移植物供体的IL28B多态性在多大程度上有助于移植后HCV的清除,从而影响对抗病毒治疗的反应。我们发现供体中的等位基因频率与欧洲人群预期的模式一致。受体中有利基因型的频率显著低于供体,合理的原因是受体代表了一组受慢性丙型肝炎影响的患者。我们的研究表明,pegIFN-α/RBV治疗HCV复发的阳性结果与供体和受体均存在有利基因型有关。然而,受体的IL28B SNP在这种临床情况下似乎起主要作用。特别是,受体中rs12979860有利基因型的纯合与持续病毒学应答相关,而与供体基因型无关。因此,鉴定这些SNP可能有助于预测肝移植患者中HCV复发感染基于干扰素治疗的反应。

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