de Ruiter PE, Gadjradj Y, de Knegt RJ, Metselaar HJ, Ijzermans JN, van der Laan LJ. Interaction of immunosuppressants with HCV antivirals daclatasvir and asunaprevir: combined effects with mycophenolic acid. World J Transplantation 2018; 8(5): 156-166 [PMID: 30211024 DOI: 10.5500/wjt.v8.i5.156]
Corresponding Author of This Article
Luc JW van der Laan, PhD, Associate Professor, Laboratory of Experimental Transplantation and Intestinal Surgery, Department of Surgery, Erasmus MC-University Medical Center, Room Na1006, Wytemaweg 80, Rotterdam CN 3015, the Netherlands. l.vanderlaan@erasmusmc.nl
Research Domain of This Article
Transplantation
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Transplantation. Sep 10, 2018; 8(5): 156-166 Published online Sep 10, 2018. doi: 10.5500/wjt.v8.i5.156
Interaction of immunosuppressants with HCV antivirals daclatasvir and asunaprevir: combined effects with mycophenolic acid
Petra E de Ruiter, Yashna Gadjradj, Robert J de Knegt, Herold J Metselaar, Jan NM Ijzermans, Luc JW van der Laan
Petra E de Ruiter, Yashna Gadjradj, Jan NM Ijzermans, Luc JW van der Laan, Department of Surgery, Erasmus MC-University Medical Center, Rotterdam CN 3015, the Netherlands
Robert J de Knegt, Herold J Metselaar, Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam CN 3015, the Netherlands
Author contributions: de Ruiter PE participated in sample and data collection and analysis and writing of the manuscript; Gadjradj Y participated in sample and data collection and analysis; de Knegt R participated in the design of the study; Metselaar HJ participated in the design of the study; IJzermans JNM participated in the design of the study; van der Laan LJW participated in the design of the study and writing of the manuscript.
Conflict-of-interest statement: All authors have no conflicts of interest to report.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Luc JW van der Laan, PhD, Associate Professor, Laboratory of Experimental Transplantation and Intestinal Surgery, Department of Surgery, Erasmus MC-University Medical Center, Room Na1006, Wytemaweg 80, Rotterdam CN 3015, the Netherlands. l.vanderlaan@erasmusmc.nl
Telephone: +31-10-7037557 Fax: +31-10-7032793
Received: April 24, 2018 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
Abstract
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 in vitro 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 via 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.
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.
