免疫抑制剂与丙型肝炎病毒抗病毒药物达卡他韦和阿舒瑞韦的相互作用：与霉酚酸的联合效应
Interaction of immunosuppressants with HCV antivirals daclatasvir and asunaprevir: combined effects with mycophenolic acid.
作者信息
de Ruiter Petra E, Gadjradj Yashna, de Knegt Robert J, Metselaar Herold J, Ijzermans Jan Nm, van der Laan Luc Jw
机构信息
Department of Surgery, Erasmus MC-University Medical Center, Rotterdam CN 3015, the Netherlands.
Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam CN 3015, the Netherlands.
出版信息
World J Transplant. 2018 Sep 10;8(5):156-166. doi: 10.5500/wjt.v8.i5.156.
AIM
To investigate the specific effects of immunosuppressants on the antiviral action of daclatasvir and asunaprevir.
METHODS
The antiviral activity of daclatasvir (DCV) and asunaprevir (ASV) combined with immunosuppressants was tested using two models for hepatitis C virus (HCV) infection.
RESULTS
Tacrolimus, rapamycin and cyclosporine did not negatively affect the antiviral action of DCV or ASV. Mycophenolic acid (MPA) showed additive antiviral effects combined with these direct acting antivirals (DAAs). MPA induces interferon-stimulated genes (ISGs) and is a potent GTP synthesis inhibitor. DCV or ASV did not induce ISGs expression nor affected ISG induction by MPA. Rather, the combined antiviral effect of MPA with DCV and ASV was partly mediated inhibition of GTP synthesis.
CONCLUSION
Immunosuppressants do not negatively affect the antiviral activity of DAAs. MPA has additive effect on the antiviral action of DCV and ASV. This combined benefit needs to be confirmed in prospective clinical trials.
目的
研究免疫抑制剂对达卡他韦和阿舒瑞韦抗病毒作用的具体影响。
方法
使用两种丙型肝炎病毒（HCV）感染模型，测试达卡他韦（DCV）和阿舒瑞韦（ASV）与免疫抑制剂联合使用时的抗病毒活性。
结果
他克莫司、雷帕霉素和环孢素对DCV或ASV的抗病毒作用没有负面影响。霉酚酸（MPA）与这些直接作用抗病毒药物（DAAs）联合使用时显示出相加的抗病毒效果。MPA可诱导干扰素刺激基因（ISGs），并且是一种有效的GTP合成抑制剂。DCV或ASV不会诱导ISGs表达，也不影响MPA对ISG的诱导。相反，MPA与DCV和ASV的联合抗病毒作用部分是通过抑制GTP合成介导的。
结论
免疫抑制剂不会对DAAs的抗病毒活性产生负面影响。MPA对DCV和ASV的抗病毒作用具有相加效应。这种联合益处需要在前瞻性临床试验中得到证实。
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