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Doctors Speak Out About Hep-C Transplants

While attending the UNOs Region 5 meeting this year, doctors brought the topic of Hep-C patients and kidney transplants to the forefront of the conversation. Would you believe that there are about 97,000 people in the USA who are waiting for a kidney transplant? And when I say waiting, I mean waiting. How about more than five years? Yes. Five years or more.

But - how about a way to increase the number of Kidneys available for these people in waiting.?

The answer is this: Getting the kidneys from a deceased donor infected with the Hepatitis C virus (HCV). Yes, I said it. Transplanting these diseased kidneys into someone else's body whose own kidney has failed. There was a trial in June of 2016. This trial showed how it is possible to cure patients of HCV who get the HCV virus from the transplant.

Up until recently, kidneys that have HCV are pretty much tossed out. Traditionally, the risk would be too high, or the organs would be too damaged. And, the HCV medication used affected the kidneys. There just was no guarantee that the transplant patient who received this HCV kidney (s) would be treatable. Over time, industry research found that just because a kidney had HCV, the organ could still be transplanted, especially if you can get rid of that HCV after transplant.

There was a chance that for some patients (note: this might fail and they might have HCV for the rest of their lives) these kidneys would be viable and the patient would not need dialysis. By opening HCV positive organs to anyone on the donor list, we could have as many as 1,000 more transplants a year. As investigations went on, they found a good number of patients were willing to go into clinical trials of this experimental transplant knowing that they would at least have a new kidney(s).

After a first round of testing this, there were about ten patients that were pretty much the first ever to test this theory. In this phase, there was only one strain of the disease used ( genotype 1). As I understand, this was due to potential treatments with a specific drug (Zepatier). Shortly after kidneys are available, genotyping must occur, and this means the lab staff had to be on call 24/7. 

During the IFN (Interferon) era, patients pursuing a kidney transplant had the option of being treated for HCV pre-transplantation but not post-transplantation due to the high rates of acute rejection attributed to IFN. HCV+ transplant candidates who did not receive treatment or who did not respond to therapy pre-transplantation had the option of listing for an HCV+ kidney. 

The individual benefit to be gained from this separation is that it reduced one's waiting time on the deceased donor waiting list due to the relatively few patients competing for an HCV+ kidney. In a study of the UNOS database from 1995-2009, Kucirka et al found that recipients of HCV+ kidneys waited 310 days fewer than the average waiting times at their center and 395 fewer days than counterparts who waited for HCV- kidneys.

From a societal perspective, there is a benefit to increasing organ utilization, to combat the ever-growing demand for kidneys. Reese et al reported that from 2005-2014, only 37% of available HCV+ kidneys were transplanted (discard rate of 67% compared to the usual discard rate of 20%).

However, the aforementioned individual and societal benefits must be weighed against several concerns for transplanting HCV+ kidneys into HCV+ recipients. Concerns include the nearly universal transmission of the virus and possible genotype super infection and also inferior patient and graft survival in patients who receive HCV+ compared to HCV- kidneys.

In the last few years, the options and outlook for kidney transplant candidates and recipients have changed dramatically with the emergence of direct-acting antiviral (DAA) therapy.


  • Patients with HCV can be efficiently and safely pre-transplantation with DAA if they have genotypes 1 or 4. Demonstrations of safe transplants can be found in the C-SURFER study where treatment with elbasvir/grasoprevir of HCV+ patients with a GFR <30 mL/min afforded a 99% cure rate and similar rates of adverse events between the placebo and study groups. In addition to elbasvir/grasoprevir, drug development continuously advances closer to DAAs becoming available for all genotypes.

  • Patients with HCV post-transplantation can also receive treatment with DAA without the risk of the rejection that typically occurs with IFN. Several case series have reported cure rates close to 100% in this new DAA era. For example, Sawinski et al reported on their experience of treating 43 patients with four different DAA regimens where ALL patients were cured (defined as a sustained virologic response 12 weeks after completing therapy). Notably, the DAA drugs have been well-tolerated. There is, however, some indication that calcineurin inhibitor levels may be affected, and so careful monitoring during DAA therapy may be warranted.

The overall effects of treating HCV post-transplantation on patient and graft survival are not yet known. The ability to administer HCV treatment post-transplantation strengthens the argument for delaying DAA treatment and listing an HCV+ kidney. In the study Sawinski mentioned earlier, patients who received HCV+ kidneys waited approximately 484 days (1.3 years) fewer than those who received HCV- kidneys. At our Nashville VA center where 20% of our transplants since December 2014 (implementation of the new Kidney Allocation System) have been HCV+ donors to HCV+ recipients, HCV+ recipients waited approximately 4.4 years fewer than HCV- recipients of HCV- kidneys (2.6 years versus seven years)

When taking into account the benefits, an algorithm for managing pre-transplantation patients with HCV was recently published in a review by Sawinski and Bloom. In summary:

 

  • Kidney transplantation candidates who are HCV RNA+ should continue to undergo liver biopsy (current practice) to exclude cirrhosis and the need for simultaneous liver-kidney transplantation. If they are not cirrhotic (Fibrosis Stage 0-3), patients with living donors should be treated with DAAs pre-transplantation.

  • In the absence of a living donor, these patients have two options. 1)Perform treatment with DAAs pre-transplantation and list for an HCV- kidney like everyone else.
    2) Delay treatment and list for both HCV+ and HCV- kidneys, then receive HCV treatment with DAAs after transplantation (note, the authors recommend consideration of the delayed treatment approach only for patients with genotype 1).

  • The late treatment approach may be particularly beneficial for patients who:
    • Expect to have a prolonged waiting time on the deceased donor list (listed in a center with long waiting time, blood type O or B)
      Those who are at high risk for health deterioration on the waiting list (patients who are elderly or diabetic).

    • For patients with advanced liver disease (Fibrosis Stage 3), HCV treatment pre-transplantation may be prudent.

 

Portions of this blog assisted by reports by Beatrice Concepcion, AJKD Social Media Advisory Board member. Follow her @KidneyBea_n.

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