Published online Sep 10, 2018. doi: 10.5500/wjt.v8.i5.156
Peer-review started: April 24, 2018
First decision: June 6, 2018
Revised: June 14, 2018
Accepted: June 27, 2018
Article in press: June 27, 2018
Published online: September 10, 2018
Processing time: 136 Days and 16.6 Hours
To investigate the specific effects of immunosuppressants on the antiviral action of daclatasvir and asunaprevir.
The antiviral activity of daclatasvir (DCV) and asunaprevir (ASV) combined with immunosuppressants was tested using two in vitro models for hepatitis C virus (HCV) infection.
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 via inhibition of GTP synthesis.
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.
Core tip: Since 2013, several new generation direct acting antivirals (DAAs) have been approved for the treatment of hepatitis C virus (HCV), including daclatasvir (DCV) and asunaprevir (ASV). Although a few reports investigated the effectivity of DAAs after liver transplantation, the effects of specific immunosuppressants on the antiviral efficacy remain largely unknown. We investigated the effect of the immunosuppressants on the antiviral action of DCV and ASV in two in vitro models for HCV. We observed that none of the immunosuppressants negatively affected the antiviral activity of these DAAs, and that mycophenolic acid has an additive effect on their antiviral action.