In a small study, doctors at Johns Hopkins have successfully transplanted 10 hepatitis C-infected kidneys into patients without hepatitis C and prevented the patients from becoming infected by hepatitis C. The success of these transplants could mean more organs being available for the nearly 100,000 people in the US currently waiting for a kidney transplant.
"Right now, most of the usable organs from donors with hepatitis C are discarded because there are very few hepatitis C-positive recipients on the waiting list," says Dr Niraj Desai, an assistant professor of surgery at Johns Hopkins University School of Medicine and senior author of the paper. "Figuring out how to use these kidneys is a way to do more transplants and save more lives."
Until recently, treating hepatitis C was difficult; treatment regiments often included weekly injections, led to serious side effects that not all patients could tolerate and didn't cure all cases of the viral infection. That meant that organs – including kidneys – from hepatitis C-positive people were considered too high-risk to transplant into patients without the virus.
Around 500 hepatitis C-positive kidneys are discarded from organ donors in the US every year, Desai says. And hundreds more may never make it to a recipient because some organ procurement organisations don't procure the kidneys in the first place due to the lack of a suitable recipient.
In the past seven years, however, a handful of new direct-acting antivirals have hit the market; the drugs cure more than 95% of all hepatitis C cases and carry few side effects. Desai and his colleagues thought it was time to try taking advantage of the new drugs to pave the way for using hepatitis C-positive kidneys for transplants.
"In this era of organ shortages, it's difficult to watch good organs get discarded," says Dr Christine Durand, an assistant professor of medicine at Johns Hopkins University School of Medicine. "This was a great opportunity to take a neglected public health resource and put it to good use."
Desai, Durand and their colleagues approached patients over age 50 who were awaiting kidney transplants, had no previous transplants and no available living donors, and were negative for hepatitis C as well as HIV and hepatitis B. Ten patients agreed to receive hepatitis C-positive kidneys. Their average age was 71 and they had been on the transplant waiting list an average of four months. All donor kidneys were recovered from donors aged 13 through 50, tested positive for hepatitis C and showed no evidence of kidney disease. The donors' blood was tested for strain and quantity of hepatitis C virus.
Each recipient received a dose of grazoprevir/elbasvir, an oral combination pill, while they were waiting to go into the operating room for their transplant. Each recipient then continued taking a daily pill of grazoprevir/elbasvir for 12 weeks after transplantation. Three patients also took a daily dose of sofosbuvir due to the strain of hepatitis found in their donor organ.
In five of the kidney recipients, there was never any hepatitis C RNA detected in their blood. In the other patients, low levels of the virus were detected shortly after transplant but then became undetectable within days or a week. No recipients ever developed any clinical signs of chronic hepatitis C infection. In addition, the kidneys themselves functioned well. At the time of the study's publication, all patients are at least a year out from their transplant and doing well, says Desai.
"This was an overwhelmingly positive study," adds Durand.
The researchers would next like to see their results replicated in a larger, multicentre trial. They say if the success of the transplants continues, it could pave the way for other hepatitis C-positive organs, including hearts and livers, to be transplanted as well.
"We're always trying to expand what we consider acceptable for an organ donor," says Durand.
Due to the opioid epidemic and deaths from drug overdoses – many of which occur in hepatitis C-positive individuals – there are an increasing number of hepatitis C-positive organs available. Being able to use these organs for transplants could mean many hundreds of lives saved each year.
"These 10 kidneys we used are 10 kidneys that would not have been transplanted outside of this study," says Desai. "They would have been discarded."
Abstract
Background: Given the high mortality rate for patients with end-stage kidney disease receiving dialysis and the efficacy and safety of hepatitis C virus (HCV) treatments, discarded kidneys from HCV-infected donors may be a neglected public health resource.
Objective: To determine the tolerability and feasibility of using direct-acting antivirals (DAAs) as prophylaxis before and after kidney transplantation from HCV-infected donors to non–HCV-infected recipients (that is, HCV D+/R− transplantation).
Design: Open-label nonrandomized trial. (ClinicalTrials.gov: NCT02781649)
Setting: Single center.
Participants: 10 HCV D+/R− kidney transplant candidates older than 50 years with no available living donors.
Intervention: Transplantation of kidneys from deceased donors aged 13 to 50 years with positive HCV RNA and HCV antibody test results. All recipients received a dose of grazoprevir (GZR), 100 mg, and elbasvir (EBR), 50 mg, immediately before transplantation. Recipients of kidneys from donors with genotype 1 infection continued receiving GZR–EBR for 12 weeks after transplantation; those receiving organs from donors with genotype 2 or 3 infection had sofosbuvir, 400 mg, added to GZR–EBR for 12 weeks of triple therapy.
Measurements: The primary safety outcome was the incidence of adverse events related to GZR–EBR treatment. The primary efficacy outcome was the proportion of recipients with an HCV RNA level below the lower limit of quantification 12 weeks after prophylaxis.
Results: Among 10 HCV D+/R− transplant recipients, no treatment-related adverse events occurred, and HCV RNA was not detected in any recipient 12 weeks after treatment.
Limitation: Nonrandomized study design and a small number of patients.
Conclusion: Pre- and posttransplantation HCV treatment was safe and prevented chronic HCV infection in HCV D+/R– kidney transplant recipients. If confirmed in larger studies, this strategy should markedly expand organ options and reduce mortality for kidney transplant candidates without HCV infection.
Authors
Christine M Durand, Mary G Bowring, Diane M Brown, Michael A Chattergoon, Guido Massaccesi, Nichole Bair, Russell Wesson, Ashraf Reyad, Fizza F Naqvi, Darin Ostrander, Jeremy Sugarman, Dorry L Segev, Mark Sulkowski, Niraj M Desai
[link url="https://www.hopkinsmedicine.org/news/media/releases/one_year_posttransplant_recipients_of_hepatitis_c_kidneys_disease_free"]Johns Hopkins Medicine material[/link]
[link url="http://annals.org/aim/article-abstract/2674335/direct-acting-antiviral-prophylaxis-kidney-transplantation-from-hepatitis-c-virus?doi=10.7326%2fM17-2871"]Annals of Internal Medicine abstract[/link]