Pascual Julio, Royuela Ana, Fernández Ana M, Herrero Ignacio, Delgado Juan F, Solé Amparo, Guirado Lluis, Serrano Trinidad, de la Torre-Cisneros Julián, Moreno Asunción, Cordero Elisa, Gallego Roberto, Lumbreras Carlos, Aguado José M
Department of Nephrology, Hospital del Mar, Barcelona, Spain.
Institut Mar for Medical Research, Barcelona, Spain.
Transpl Infect Dis. 2016 Dec;18(6):819-831. doi: 10.1111/tid.12601. Epub 2016 Oct 19.
Appropriate post-transplant immunosuppressive regimens that avoid acute rejection, while reducing risk of viral reactivation, have been sought, but remain a chimera. Recent evidence suggesting potential regulatory and antiviral effects of mammalian target of rapamycin inhibitors (mTORi) is of great interest. Although the concept of an immunosuppressive drug with antiviral properties is not new, little effort has been made to put the evidence together to assess the management of immunosuppressive therapy in the presence of a viral infection. This review was developed to gather the evidence on antiviral activity of the mTORi against the viruses that most commonly reactivate in adult solid organ recipients: cytomegalovirus (CMV), polyomavirus, Epstein-Barr virus (EBV), human herpesvirus 8 (HHV8), and hepatitis C virus (HCV). A rapid review methodology and evaluation of quality and consistency of evidence based on the GRADE system was used. The existing literature was variable in nature, although indicating a potential advantage of mTORi in CMV, polyomavirus, and HHV8 infection, and a most doubtful relation with EBV and HCV infection. Several recommendations about the management of these infections are presented that can change certain current patterns of immunosuppression and help to improve the prognosis of the direct and indirect effects of viral infection in solid organ recipients.
人们一直在寻找合适的移植后免疫抑制方案,既能避免急性排斥反应,又能降低病毒再激活的风险,但这仍然是一个难以实现的目标。最近有证据表明雷帕霉素靶蛋白抑制剂(mTORi)具有潜在的调节和抗病毒作用,这引起了人们极大的兴趣。尽管具有抗病毒特性的免疫抑制药物这一概念并不新鲜,但很少有人努力综合证据来评估在病毒感染情况下免疫抑制治疗的管理。本综述旨在收集有关mTORi对成年实体器官受者中最常见再激活病毒的抗病毒活性的证据:巨细胞病毒(CMV)、多瘤病毒、爱泼斯坦-巴尔病毒(EBV)、人类疱疹病毒8型(HHV8)和丙型肝炎病毒(HCV)。采用了基于GRADE系统的快速综述方法以及证据质量和一致性评估。现有文献性质各异,不过表明mTORi在CMV、多瘤病毒和HHV8感染方面具有潜在优势,而与EBV和HCV感染的关系则很可疑。本文提出了一些关于这些感染管理的建议,这些建议可以改变当前某些免疫抑制模式,并有助于改善实体器官受者中病毒感染直接和间接影响的预后。