Direct-Acting-Antivirals Anti-hepatitis C Virus in Renal Transplant Patients: Relevance of Pharmacologic Interaction

Main Article Content

Maurizio Salvadori
Aris Tsalouchos

Keywords

Direct Antiviral Agents; HCV related diseases; Immunosuppressants; Metabolic pathways; Post-Transplant complications

Abstract

Renal transplantation in patients affected by hepatitis C virus (HCV) infection has been a serious problem becauseof the use of immunosuppres-sants. HCV virus may be more aggressive in both the liver and the kidney. Several posttransplantation pathologies are known to be ascribed to the HCV virus.
Virus eradication has been historically attempted with interferon (IFN) and ribavirin with poor results. In addition, IFN given posttransplan-tation may cause severe acute rejection.
The introduction of direct antiviral agents (DAA) has revolutionized the treatment, and now it is possible to treat renal transplant patients with these agents leading to a HCV-free status in 3 months without the use of IFN.
The major problem caused by these agents is their interference with the immunosuppressive agents.
The pharmacokinetics of DAA and immunosuppressants often meet the same metabolic pathways and use the same cytochromes or proteic complexes. In some cases, this may lead to high or low immunosuppressant levels with the risk of rejection. In other cases, the DAAs are inter-ested and they may be increase or decrease in a dangerous way. Therefore a strict monitoring is always recommended.

Downloads

Download data is not yet available.
Abstract 297 | PDF Downloads 64 HTML Downloads 7 XML Downloads 40

References

1. Zylberberg H, Nalpas B, Carnot F, Skhiri H, Fontaine H, Legendre C, et al. Severe evolution of chronic hepatitis C in renal transplantation. A case control study. Nephrol Dial Transplant. 2002;17 (1):129–33. http://dx.doi.org/10.1093/ndt/17.1.129
2. Mitwalli AH, Alam A, al-Wakeel J, al Suwaida K, Tarif N, Schaar TA, et al. Effect of chronic viral hepatitis on graft survival in Saudi renal transplant patients. Nephron Clin Pract. 2006;102 (2):c72–80. http://dx.doi.org/10.1159/000089090
3. Fabrizi F, Martin P, Dixit V, Bunnapradist S, Kanwal F, Dulai  G. Post-transplant diabetes mellitus and HCV seropositive status after renal transplantation. Meta-analysis of clinical studies. Am J Transplant. 2005;5(10):2433–40. http://dx.doi. org/10.1111/j.1600-6143.2005.01040.x
4. Burra P, Buda A, Livi U, Rigotti P, Zanus G, Calabrese F, et al. Occurrence of post-transplant lymphoproliferative disorders among over thousand adult recipients: Any role for hepatitis C infection? Eur J Gastroenterol Hepatol. 2006;18(10):1065–70. http://dx.doi.org/10.1097/01.meg.0000231752.50587.ae
5. Cruzado JM, Carrera M, Torras J, Grinyó JM. Hepatitis  C virus infection and de novo glomerular lesions in renal allografts. Am J Transplant. 2001;1(2):171–8. http://dx.doi. org/10.1034/j.1600-6143.2001.10212.x
6. Morales JM, Pascual-Capdevila J, Campistol JM, Fernandez-Zatarain G, Munoz MA, Andres A, et al. Membranous glomerulonephritis associated with hepatitis C virus infection in renal transplant patients. Transplantation. 1997;63(11):1634–9. http:// dx.doi.org/10.1097/00007890-199706150-00017
7. Perico N, Cattaneo D, Bikbov B, Remuzzi G. Hepatitis C infection and chronic renal diseases. Clin Am Soc Nephrol. 2009;4(1):207–20. http://dx.doi.org/10.2215/CJN.03710708
8. Baid-Agrawal S, Farris AB, Pascual M, Mauiyyedi S, Farrell  ML, Tolkoff-Rubin N, et al. Overlaping pathways to transplant glomerulopathy: Chronic humoral rejection, hepatitis C infection and thrombotic microangiopathy. Kid Int. 2011;80(8):879–85. http://dx.doi.org/10.1038/ki.2011.194
9. Baid S, Tolkoff-Rubin N, Saidman S, Chung R, Williams WW, Auchincloss H, et al. Acute humoral rejection in hepati-tis C-infected renal transplant recipients receiving antiviral therapy. Am J Transplant. 2003;3(1):74–8. http://dx.doi. org/10.1034/j.1600-6143.2003.30113.x
10. Aghemo A, de Francisco R. New horizons in hepatitis C antiviral therapies with directacting antiviral. Hepatology. 2013;58(1):428–38. http://dx.doi.org/10.1002/hep.26371
11. Yau A, Yoshida E. Hepatitis C drugs: The end of the pegylated interferon era and the emergence of all-oral interferon-free anti-viral regimens: A concise review. Can J Gastroenterol Hepatol. 2014;28(8):445–51. http://dx.doi.org/10.1155/2014/549624
12. AASLD-IDSA. American Association for the Study of Liver Diseases/Infectious Disease Society of America joint guidelines, recommendations for testing, managing, and treating hepatitis  C [Internet]. [cited 2020 Feb 26]. Available from: www.hcvguidelines.org
13. Belga S, Doucette KE. Hepatitis C in non-hepatic solid organ transplant candidates and recipients: A new horizon. World J Gastroenterol. 2016;22(4):1650–63. http://dx.doi.org/10.3748/ wjg.v22.i4.1650
14. Salvadori M, Tsalouchos A. Hepatitis C and renal trans-plantation in era of new antiviral agents.World J Transplant. 2018;8(4):84–96. http://dx.doi.org/10.5500/wjt.v8.i4.84
15. Jadoul M, Berenguer MC, Doss W, Fabrizi F, Izopet J, Jha V, et  al. Executive summary of the 2018 KDIGO hepatitis C in CKD guideline: Welcoming advances in evaluation and management. Kidney Int. 2018;94(4):663–73. http://dx.doi. org/10.1016/j.kint.2018.06.011
16. KDIGO clinical practice guideline on the evaluation and management of candidates for kidney transplantation. Transplantation. 2020;104(4S):S57–8.
17. Dresser GK, Spence JD, Bailey DG. Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet. 2000;38(1):41–57. http://dx.doi.org/10.2165/00003088-200038010-00003
18. Marquez B, van Bambeke F. ABC multidrug transporters: Target for modulation of drug pharmacokinetics in drug–drug interactions. Curr Drug Targets. 2011;12(5):600–20. http://dx. doi.org/10.2174/138945011795378504
19. European Association for the Study of the Liver. EASL recom-mendations on treatment of hepatitis C 2018. J Hepatol. 2018. http://dx.doi.org/10.1016/j. jhep.2018.03.026
20. Hill L. Hepatitis C virus direct-acting antiviral drug interactions and use in renal and hepatic impairment. Top Antivir Med. 2015;23(2):92–6.
21. Ouwerkerk-Mahadevan S, Snoeys J, Peeters M, Beumont-Mauviel M, Simion A. Drug–drug interactions with the NS3/4A protease inhibitor simeprevir. Clin Pharmacokinet. 2016;55(2):197–208. http://dx.doi.org/10.1007/s40262-015-0314-y
22. Colombo M, Aghemo A, Liu H, Zhang J, Dvory-Sobol H, Hyland R, et al. Treatment with ledipasvir-sofosbuvir for 12 or 24 weeks in kidney transplant recipients with chronic hepatitis C virus genotype 1 or 4 infection: A randomized trial. Ann Intern Med. 2017;166(2):109–17. http://dx.doi.org/10.7326/M16-1205
23. Reau N, Kwo PY, Rhee S, Brown RS Jr, Agarwal K, Angus P, et  al. Glecaprevir/pibrentasvir treatment in liver or kidney transplant patients with hepatitis C virus infection. Hepatology. 2018;68(4):1298–307. http://dx.doi.org/10.1002/hep.3004
24. Fernández-Ruiz M, Polanco N, García-Santiago A, Muñoz R, Hernández AM, González E, et al. Impact of anti-HCV direct antiviral agents on graft function and immunosuppressive drug levels in kidney transplant recipients: A call to attention in the mid-term follow-up in a single-center cohort study. Transplant Int. 2018;31(8):887–99. http://dx.doi.org/10.1111/tri.13118
25. Kwo PY, Badshah MB. New hepatitis C virus therapies: Drug classes and metabolism, drug interactions relevant in the transplant settings, drug options in decompensated cirrhosis, and drug options in end-stage renal disease. Curr Opin Organ Transplant. 2015;20(3):235–41. http://dx.doi.org/10.1097/MOT. 0000000000000198
26. Kwo PY, Mantry PS, Coakley E, Te HS, Vargas HE, Brown R Jr, et al. An interferon free antiviral regimen for HCV after liver transplantation. N Engl J Med. 2014;371(25):2375–82. http://dx. doi.org/10.1056/NEJMoa1408921