Cyclosporine suppresses hepatitis C virus in vitro and increases the chance of a sustained virological response after liver transplantation
Cyclosporine suppresses hepatitis C virus in vitro and increases the chance of a sustained virological response after liver transplantation
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DOI：
10.1002/lt.20532
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发表时间：
2006-01-01
影响因子：
4.6
通讯作者：
Nelson, DR
中科院分区：
文献类型：
--
作者：
Firpi, RJ;Zhu, HZ;Nelson, DR
环孢素是一种免疫抑制剂，广泛用于肝移植受者的管理。环孢霉素已被证明对HIV、单纯疱疹病毒和牛痘病毒具有抗病毒活性。本研究的目的是确定环孢素在肝移植受者在干扰素和利巴韦林联合治疗期间的病毒清除效果，并确定环孢素在体外的抗病毒潜力。免疫抑制包括环孢霉素或他克莫司为基础的治疗。两组均接受干扰素和利巴韦林治疗48周，当确定有进行性组织学疾病的证据时。我们发现，以环孢霉素为基础的免疫抑制治疗组（n = 56）的持续病毒学应答率为46%，而以他克莫司为基础的治疗组为27%（n=59，P = 0.03）。进行体外研究以评价环孢霉素在复制子系统中的抗病毒作用。这些研究表明，环孢菌素以剂量依赖性方式抑制丙型肝炎病毒复制。环孢霉素与干扰素联用具有相加效应，其作用不依赖于干扰素信号通路。总之，在接受以干扰素为基础的治疗的患者中，环孢霉素可能比他克莫司更有优势，应在前瞻性随机试验中进行研究。
Cyclosporine is an immunosuppressive agent widely used in the management of liver transplant recipients. Cyclosporine has been shown to have antiviral activities against HIV, herpes simplex, and vaccinia viruses. The aim of this study was to determine the effect of Cyclosporine in viral clearance in the liver transplant recipients during therapy with combination of interferon and ribavirin, and to determine the anti-viral potential of Cyclosporine in vitro. Immunosuppression consisted of either Cyclosporine or Tacrolimus-based therapy. Both groups received therapy with interferon and ribavirin for 48 weeks when evidence of progressive histologic disease was determined. We found that subjects on Cyclosporine-based immunosuppression (n = 56) had a higher sustained virological response of 46% compared to 27% in the patients on Tacrolimus-based therapy (n=59, P = 0.03). In vitro studies were performed to evaluate the antiviral effect of Cyclosporine in the replicon system. These studies showed that Cyclosporine inhibits hepatitis C viral replication in a dose-dependent manner. Combination of Cyclosporine with interferon showed additive effect, and its function is independent of interferon signaling pathways. In conclusion, Cyclosporine may offer an advantage to Tacrolimus in those patients undergoing interferon-based therapy and should be studied in a prospective randomized trial.