[Photo by Bill Branson, NIH Medical Arts, National Institutes of Health. Pictured are Robert Colbert, M.D., Ph.D., Amy Petrik, Ph.D., and Grace Kwon, Ph.D. ]
By Martina M. McGrath, MD
May 4, 2017
Currently, over 97,000 patients are awaiting kidney transplant.1 Hepatitis C (HCV) infection is prevalent in the community, and it has been reported that >3000 kidneys from HCV+ donors were offered between 2005 and 2014.2 Prior to the current era of direct-acting antiviral agents (DAAV), patients with HCV who underwent renal transplantation had poorer outcomes, and antiviral treatment with interferon was associated with increased risk of rejection. Likely related to these risks, it has been reported that over 500 kidneys from HCV+ donors are discarded annually.2 However, DAAVs have transformed the management of HCV infection. Greater than 90 percent cure rates have been reported with many of these medications, which are generally well-tolerated. With the availability of safe and effective antiviral therapy for HCV, the question has arisen, could these kidneys now be safely used in HCV-negative recipients?
A research group at University of Pennsylvania, led by Dr. Peter Reese, presented the results of a provocative study at the American Transplant Congress (ATC) this week, and the study was simultaneously published in The New England Journal of Medicine (NEJM). They report transplantation of HCV-positive deceased-donor kidneys into 10 HCV negative recipients with six-month follow up.3 They used a very carefully designed protocol restricted to genotype 1 HCV positive donors, the subtype most effectively treated by most DAAVs.
Enrolled patients in overall good health, who had to be accepted as suitable candidates for liver transplantation if required, were all <18 months on dialysis and at low risk of rejection. All were awaiting their first transplants and were unsensitized, with no pre-formed anti-HLA antibodies. Donor kidneys were of good quality with KDPI scores mostly <50%. Standard immunosuppression was given with Thymoglobulin and steroid induction, and maintenance with tacrolimus, mycophenolate mofetil, and prednisone.
Patients were prospectively monitored for HCV infection and the development of resistance. All recipients developed a detectable HCV viral load by day three, with widely variable peak viral loads. Two patients developed elevated transaminases. All patients were treated with elbasvir-grazoprevir, initiated at diagnosis of HCV infection, and were cured of HCV infection, defined as a sustained virologic response 12 weeks after completion of treatment. Renal outcomes were generally excellent, with mean creatinine at six months of 1.1mg/dL. One patient did develop proteinuria and biopsy proven FSGS during the follow-up period; the significance of this is unclear.
So what does this mean? Given the scarcity of donated organs and the frequency of death on the waitlist, strategies that could improve the available supply of high-quality organs are much needed. DAAVs proved highly effective, even in very immunosuppressed patients, and the short-term outcomes are very promising. However, the potential to induce a very serious infection at a time of intensive immunosuppression carries significant risk. Such a strategy also demands a rigorous process of obtaining informed consent from patients, as was undertaken in this study.3
While these findings hold promise, this was a carefully conducted clinical study with highly selected donors and recipients, and it cannot be assumed that this data is generalizable to the standard population awaiting organ transplantation. These data represent an exciting proof of concept study, but will require long-term follow up and replication in a much larger patient cohort before the safety of this approach is established. In the interim, the findings do emphasize that HCV+ kidneys can give excellent function and their use in HCV+ recipients needs to be promoted while we await more data on their use in HCV-negative patients.
- https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/#. (Accessed 05/03/17)
- Reese PP, Abt PL, Blumberg EA, Goldberg DS. Transplanting Hepatitis C-Positive Kidneys. The New England Journal of Medicine 2015;373:303-5.
- Goldberg DS. Trial of Transplantation of HCV-Infected Kidneys into Uninfected Recipients. The New England Journal of Medicine 2017. Published online April 30th 2017, DOI 10.1056/NEJMc1705221.
Dr. Martina McGrath is an Instructor in Medicine at Harvard Medical School, and a member of the Renal Division, Department of Medicine, at Brigham and Women’s Hospital, both in Boston. Dr. McGrath is the Medical Editor for the Trends in Medicine blog.