Recipients of HCV-positive kidneys remain HCV-negative 1 year after transplant

John Murphy, MDLinx | March 21, 2018

Surgeons who prophylactically administered direct-acting antivirals (DAAs) to 10 kidney transplant recipients successfully prevented the patients from becoming infected from organ donors with hepatitis C virus (HCV).

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Transplant recipients were disease-free 12 weeks after receiving prophylactic antivirals with HCV-positive donor kidneys.

This strategy could make donor organs much more widely available and reduce mortality for people on the kidney transplant waiting list, researchers concluded in a recent article published in Annals of Internal Medicine.

“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,” said senior author Niraj Desai, MD, assistant professor of surgery, Johns Hopkins University School of Medicine, Baltimore, MD. “Figuring out how to use these kidneys is a way to do more transplants and save more lives.”

In their paper, Dr. Desai and colleagues noted that 2,698 HCV-positive donor kidneys that were harvested for transplant between 2005 and 2014 were discarded.

“These 10 kidneys we used are 10 kidneys that would not have been transplanted outside of this study,” Dr. Desai said. “They would have been discarded.”

Other researchers have transplanted HCV-positive kidneys into uninfected patients, but this is the first one to use DAAs both before and after transplantation to prevent infection in HCV-negative patients.

Prophylactic DAAs

For this trial, Dr. Desai and colleagues at Johns Hopkins recruited 10 patients over age 50 (median age: 71) who were on the kidney transplant waiting list and had no living donors available. Subjects tested negative for HCV, hepatitis B virus, and HIV.

Kidneys came from deceased donors aged 13 to 50 years (median age: 30) who had positive HCV antibody and HCV RNA tests. Donors were also tested for HCV genotype strain. Six of the 10 donors had died from a drug overdose, “reflecting the national opioid epidemic,” the authors noted.

Just before transplantation surgery, all 10 recipients received an oral dose of grazoprevir 100 mg/elbasvir 50 mg.

For 12 weeks after transplantation, all recipients continued taking a daily dose of grazoprevir/elbasvir. Three patients who received a donor organ with a virus strain other than genotype 1 (the most common strain) also took a daily dose of sofosbuvir 400 mg for 12 weeks.

Within 24 hours of transplantation, three recipients had detectable levels of HCV RNA. But within a week or so, HCV RNA was undetectable in all three.

After 12 weeks of treatment, no HCV RNA was detected in any recipient. No recipients developed any clinical sign of virologic or chronic HCV infection.

Currently, all patients have reached the 1-year mark since transplantation and are doing well, Dr. Desai noted.

The researchers called for carefully monitored clinical trials to further investigate this approach. If confirmed in larger studies, this research could pave the way for transplanting other HCV-positive organs, including hearts and livers, they predicted.

“In this era of organ shortages, it’s difficult to watch good organs get discarded,” said study coauthor Christine Durand, MD, assistant professor of medicine, Johns Hopkins University School of Medicine. “This was a great opportunity to take a neglected public health resource and put it to good use.”

This research was supported in part by Merck Sharp & Dohme Corp., which also provided the study drug. Individual researchers were supported by grants from the National Cancer Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institute of Allergy and Infectious Disease.

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