Kidney transplants are the best treatment for end-stage renal disease (ESRD), with better survival outcomes than haemodialysis or peritoneal dialysis.¹Chau K. Hong Kong Med J. 2018;24(1):4-5. However, in Hong Kong as well as much of the rest of the world, there is an increasing gap between the number of patients requiring a transplant and the number of organs available.^1,2Chau K. Hong Kong Med J. 2018;24(1):4-5.
Augustine J. Cleve Clin J Med. 2018;85(2):138-144. While live donor transplants are one avenue to increase the supply of donor organs, not all patients are fortunate enough to identify living donors.³Ruck JM et al. Curr Opin Nephrol Hypertens. 2018;27(6):445-453. As a result, suboptimal organs that may still confer a substantial survival benefit are now being considered for transplantation.³Ruck JM et al. Curr Opin Nephrol Hypertens. 2018;27(6):445-453. This donor pool includes those of “increased risk” donors (IRDs), which includes donors positive for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). IRDs account for almost 20% of the deceased donor pool.³Ruck JM et al. Curr Opin Nephrol Hypertens. 2018;27(6):445-453.

The results of the MYTHIC trial, demonstrating the safety and efficacy of an 8-week treatment regimen of glecaprevir and pibrentasvir (G/P) initiated as early as 2 days after kidney transplantation of a HCV-viremic donor to a HCV-uninfected recipient were recently published in the Journal of the American Society of Nephrology.⁴Sise ME et al. J Am Soc Nephrol. Published online August 25, 2020.

MYTHIC was an open-label interventional study conducted at seven transplant centres in the United States.⁴Sise ME et al. J Am Soc Nephrol. Published online August 25, 2020. The primary objective was to demonstrate the safety and efficacy via sustained virologic response at 12 weeks (SVR12) of an 8-week shortened course treatment regimen of G/P initiated as early as 2 days after transplantation of a kidney from a HCV-viremic donor into a HCV-uninfected patient.⁴Sise ME et al. J Am Soc Nephrol. Published online August 25, 2020. Secondary objectives included time to transplant, key clinical outcomes including patient survival, graft failure, acute allograft rejection, delayed graft function, estimated glomerular filtration rate (eGFR), proteinuria, and safety as defined by serious adverse events (AEs).⁴Sise ME et al. J Am Soc Nephrol. Published online August 25, 2020. Patients received co-formulated glecaprevir 300mg and pibrentasvir 120mg tablets once daily for 8 weeks.⁴Sise ME et al. J Am Soc Nephrol. Published online August 25, 2020. Eligible patients were between ≥21 and ≤65 years of age with an eGFR of <15mL/min/1.73m² or were on dialysis.⁴Sise ME et al. J Am Soc Nephrol. Published online August 25, 2020.

Out of 63 eligible patients, a total of 30 patients received a kidney transplant from an HCV-viremic donor through the course of the study.⁴Sise ME et al. J Am Soc Nephrol. Published online August 25, 2020. The median age of the eligible patients was 57 years, of which 62% were men, and the majority (87%) were on dialysis.⁴Sise ME et al. J Am Soc Nephrol. Published online August 25, 2020. The median donor age was 34, and the median donor terminal creatinine was 1.0mg/dL for the 30 allografts.⁴Sise ME et al. J Am Soc Nephrol. Published online August 25, 2020.

The 30 kidney transplant recipients had a median post-transplant follow up of 35.6 weeks.⁴Sise ME et al. J Am Soc Nephrol. Published online August 25, 2020. G/P treatment was started between days 2 and 5 post-transplant in all participants.⁴Sise ME et al. J Am Soc Nephrol. Published online August 25, 2020. All patients experienced rapid decline in HCV RNA, and all 30 recipients achieved SVR12.⁴Sise ME et al. J Am Soc Nephrol. Published online August 25, 2020. By week 1 of therapy, only 12 of 30 patients had detectable viral load, and by week 4, no patients had detectable viral loads.⁴Sise ME et al. J Am Soc Nephrol. Published online August 25, 2020.

The overall survival and graft survival were 97%. A total of 23% of kidney recipients had delayed graft function.⁴Sise ME et al. J Am Soc Nephrol. Published online August 25, 2020. Graft function at 6 months was described as excellent, and median creatinine was 1.2mg/dL, and median eGFR 57mL/min/1.73m².⁴Sise ME et al. J Am Soc Nephrol. Published online August 25, 2020. The G/P co-formulation was well tolerated in the post-transplant period, with the most common AEs being dizziness, hypertension, hyperglycaemia, hyperkalaemia, hypotension, nausea, and vomiting.⁴Sise ME et al. J Am Soc Nephrol. Published online August 25, 2020. None of the 30 recipients experienced clinically significant hepatic enzyme elevations after transplant, which were defined as alanine aminotransferase (ALT) ≥5 times the upper limit of normal.⁴Sise ME et al. J Am Soc Nephrol. Published online August 25, 2020.