Hepatitis C-infected kidneys safely transplanted into uninfected recipients

Last Updated: 2018-08-07

By Will Boggs MD

NEW YORK (Reuters Health) - Uninfected recipients can safely undergo transplant with kidneys infected with genotype 1 hepatitis C virus (HCV) followed by direct-acting antiviral therapy, according to results from the open-label, nonrandomized THINKER trial.

"What we found most interesting was that these 20 THINKER patients - all of whom were highly immunosuppressed after kidney transplantation - rapidly responded to antiviral therapy - meaning that their HCV viral loads declined steadily even in the first weeks after transplant," said Dr. Peter P. Reese of the University of Pennsylvania, in Philadelphia.

"This finding gave us great reassurance that antiviral medications, such as elbasvir/grazoprevir, can effectively cure HCV infection even in the setting of a very suppressed immune system," he told Reuters Health by email.

Waiting times for deceased-donor kidney transplants exceed five years in many areas, but hundreds of kidneys from donors with hepatitis C are discarded each year and many more are not procured because of concern that no transplant center would accept them.

Dr. Reese and colleagues evaluated HCV treatment outcomes, estimated glomerular filtration rate (GFR), and quality of life among 20 uninfected recipients of HCV-infected kidneys who also received elbasvir-grazoprevir beginning on posttransplant day 3.

All 20 recipients had newly detectable HCV RNA as late as postoperative day 5, but HCV RNA was undetectable within four weeks of initiation of HCV therapy in all 20 recipients, the researchers report in Annals of Internal Medicine, online August 7.

All participants achieved sustained virologic response at 12 weeks with their initial course of treatment, and the first 10 participants have remained HCV-negative 12 months after transplant.

No patients experienced allograft rejection, although some developed weakly positive donor-specific antibodies.

Quality-of-life physical scores declined at four weeks but then increased steadily to above-pretransplant levels, whereas mental scores decreased at four weeks and returned to baseline by 12 months.

Estimated GFRs six and 12 months posttransplant were significantly better for these participants than for comparable patients who received HCV-negative kidneys.

"This finding suggests that donor HCV did not meaningfully harm the quality of these kidneys," Dr. Reese said. "This finding is important because in the past, many kidneys from HCV-infected donors were discarded in part because people thought they were lower quality, that HCV would have injured the donor kidneys."

"The transplant community should recognize the kidneys from HCV-infected donors are very valuable and should be used as much as possible to bring transplants to more people," he said. "Because of the opiate crisis, a growing number of potential organ donors have HCV. Their families and loved ones hope that these individuals can become organ donors. Their organs should not go to waste."

"I also very much hope that Medicare and other insurance companies will create payment pathways for HCV medications after transplant," Dr. Reese said. "That is a necessary step for this form of transplantation to one day become standard of care. In the future, only with insurance support can transplant centers offer HCV-infected organs to their patients and have confidence that their patients will be able to be cured of HCV after transplant."

Dr. Adnan Sharif from Queen Elizabeth Hospital and the University of Birmingham, in the U.K., who wrote an accompanying editorial, told Reuters Health by email, "We remain very conservative in our policies for organ utilization and think the evidence from Reese and colleagues demonstrates how good short-term outcomes are for kidneys from donors with hepatitis C."

"Rather than the high discard rates, potential recipients (with adequate counselling) will benefit from these kidneys and have successful short-term outcomes (and likely improved longer-term outcomes compared to the alternative)," he said. "Counselling potential recipients to take these kidneys (which are usually of better quality) versus possible marginal kidneys (e.g., older kidneys, more medical co-morbidities) allows patients to choose their preference in light of existing evidence."

"A critical review of existing evidence is sufficient to develop a strategy to increase our use of kidneys from donors with hepatitis C (into recipients without hepatitis C)," Dr. Sharif said. "Physicians must remember that the alternative to a kidney transplant is to remain on dialysis, which is expensive, associated with poor quality of life for many and increased mortality. I also see no reason why the scope of organ utilization should not be extended to other organs like heart, lung, and maybe even liver (if no evidence of damage)."

Dr. Meghan Elizabeth Sise from Massachusetts General Hospital, in Boston, recently reviewed the status of transplantation of HCV-infected kidneys into uninfected recipients. She told Reuters Health by email, "So far, HCV has been cured in all cases post kidney transplant when direct-acting antivirals are administered in the early post-transplant period (within 3 days). Post-transplant outcomes have been excellent in these patients."

"Transplant leaders need to work together to create guidelines and best practices to make HCV+ to HCV- transplantation more common to cut down on unnecessary discard of high-quality HCV+ deceased-donor kidneys," said Dr. Sise, who was not involved in the new study.

"Insurers should consider covering the cost of direct-acting antiviral medications posttransplant since shortening the time on dialysis is likely to be cost-saving," Dr. Sise added.

Merck & Co., which sells elbasvir-grazoprevir as Zepatier, provided the drug and funds for study activities and had various relationships with six of the authors, including Dr. Reese.

SOURCE: https://bit.ly/2M3hdZD

Ann Intern Med 2018.