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Updated View on Kidney Transplant from HCV-Infected Donors and DAAs
Fabrizio Fabrizi1, Roberta Cerutti1, Carlo M Alfieri1,2
1Division of Nephrology, Dialysis and Kidney Transplant, Ca' Granda IRCCS Foundation and Maggiore Policlinico Hospital, 20137 Milano, Italy.
Insights
Kidney transplants from hepatitis C virus (HCV)-infected donors to HCV-naïve recipients are safe and effective when using direct-acting antiviral agents (DAAs). This approach can significantly reduce transplant waiting times and mortality for patients needing a kidney.
Area of Science:
- Nephrology
- Hepatology
- Transplant Surgery
Background:
- Global kidney shortage leads to increased mortality in dialysis patients.
- Transplanting kidneys from hepatitis C virus (HCV)-infected donors into HCV-naïve recipients is a growing strategy.
- Direct-acting antiviral agents (DAAs) offer a potential solution for managing HCV infection post-transplant.
Purpose of the Study:
- To review the efficacy and safety of kidney transplantation from HCV-viremic donors to HCV-naïve recipients.
- To evaluate outcomes when recipients receive early antiviral therapy with DAAs.
Main Methods:
- Extensive literature review of published studies (n=11, n=201 patients) within the last three years.
- Analysis of various DAA combinations (elbasvir/grazoprevir, glecaprevir/pibrentasvir, sofosbuvir-based regimens).
- Assessment of DAA initiation timing relative to renal transplant (RT).
Main Results:
- Sustained virological response (SVR) rates ranged from 97.5% to 100%.
- Few severe adverse events (SAEs) were reported, including fibrosing cholestatic hepatitis, elevated aminotransferases, and acute rejection.
- Adverse events may be linked to HCV transmission, DAAs, or the transplant procedure itself; early DAA initiation might reduce AEs.
Conclusions:
- Evidence supports expanding the kidney donor pool using HCV-infected donor organs.
- Kidney transplants from HCV-viremic donors should be conducted within research protocols to generate real-world evidence.
- Pangenotypic DAAs enhance the viability of HCV-viremic donors as a significant resource for kidney transplantation.
Background:
The discrepancy between the number of potential available kidneys and the number of patients listed for kidney transplant continues to widen all over the world. The transplant of kidneys from hepatitis C virus (HCV)-infected donors into HCV naïve recipients has grown recently because of persistent kidney shortage and the availability of direct-acting antiviral agents. This strategy has the potential to reduce both waiting times for transplant and the risk of mortality in dialysis.
Aim:
We made an extensive review of the scientific literature in order to review the efficacy and safety of kidney transplant from HCV-viremic donors into HCV naïve recipients who received early antiviral therapy with direct-acting antiviral agents (DAAs).
Results:
Evidence has been rapidly accumulated on this topic and some reports have been published (n = 11 studies, n = 201 patients) over the last three years. Various combinations of DAAs were administered-elbasvir/grazoprevir (n = 38), glecaprevir/pibrentasvir (n = 110), and sofosbuvir-based regimens (n = 53). DAAs were initiated in a range between a few hours before renal transplant (RT) to a median of 76 days after RT. The sustained virological response (SVR) rate was between 97.5% and 100%. A few severe adverse events (SAEs) were noted including fibrosing cholestatic hepatitis (n = 3), raised serum aminotransferase levels (n = 11), and acute rejection (n = 7). It remains unclear whether the AEs were related to the transmission of HCV, the use of DAAs, or kidney transplant per se. It appears that the frequency of AEs was greater in those studies where DAAs were not given in the very early post-kidney transplant phase.
Conclusions:
The evidence gathered to date encourages the expansion of the kidney donor pool with the adoption of HCV-infected donor organs. We suggest that kidney transplants from HCV-viremic kidneys into HCV-uninfected recipients should be made in the context of research protocols. Many of the studies reported above were externally funded and we need research generating "real-world" evidence. The recent availability of pangenotypic combinations of DAAs, which can be given even in patients with eGFR < 30/min/1.73 m2, will promote the notion that HCV-viremic donors are a significant resource for kidney transplant.
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