Kidneys from deceased donors with hepatitis C virus (HCV) infection can be safely transplanted into non-infected recipients when a regimen of direct-acting antiviral therapies is initiated as early as two days after the transplant, according to a clinical trial study “Multicenter Study to Transplant Hepatitis C–Infected Kidneys (MYTHIC): An Open-Label Study of Combined Glecaprevir and Pibrentasvir to Treat Recipients of Transplanted Kidneys from Deceased Donors with Hepatitis C Virus Infection” from Massachusetts General Hospital (MGH) and reported in the Journal of the American Society of Nephrology.

MGH researchers found that each of 30 kidney recipients were cured of HCV with no serious side effects attributable to the antiviral therapy, and that nearly all maintained excellent allograft function at six months.

“Single-center trials and retrospective case series have reported promising outcomes using kidneys from donors with hepatitis C virus (HCV) infection. However, multicenter trials are needed to determine if those findings are generalizable,” write the investigators.

“We conducted a prospective trial at seven centers to transplant 30 kidneys from deceased donors with HCV viremia into HCV-uninfected recipients, followed by 8 weeks of once-daily coformulated glecaprevir and pibrentasvir, targeted to start 3 days posttransplant. Key outcomes included sustained virologic response (undetectable HCV RNA 12 weeks after completing treatment with glecaprevir and pibrentasvir), adverse events, and allograft function.”

“We screened 76 patients and enrolled 63 patients, of whom 30 underwent kidney transplantation from an HCV-viremic deceased donor (median kidney donor profile index, 53%) in May 2019 through October 2019. The median time between consent and transplantation of a kidney from an HCV-viremic donor was 6.3 weeks. All 30 recipients achieved a sustained virologic response. One recipient died of complications of sepsis 4 months after achieving a sustained virologic response.”

“No severe adverse events in any patient were deemed likely related to HCV infection or treatment with glecaprevir and pibrentasvir. Three recipients developed acute cellular rejection, which was borderline in one case. Three recipients developed polyomavirus (BK) viremia near or >10,000 copies/ml that resolved after reduction of immunosuppression. All recipients had good allograft function, with a median creatinine of 1.2 mg/dl and median eGFR of 57 ml/min per 1.73 m2 at 6 months.”

“Our multicenter trial demonstrated safety and efficacy of transplantation of 30 HCV-viremic kidneys into HCV-negative recipients, followed by early initiation of an 8-week regimen of glecaprevir and pibrentasvir.”

“We successfully treated the hepatitis C virus in kidneys transplanted from HCV-positive donors by using the antiviral agents glecaprevir and pibrentasvir as part of an eight-week course of daily dosing,” says Meghan Sise, MD, investigator in the Division of Nephrology at MGH and co-first author of the study. “These findings could carry a strong message to the many transplant centers that are still wary about or resistant to using kidneys from HCV-infected donors. We’ve shown that these so-called donor positive to recipient negative transplants can be done safely and effectively through early antiviral intervention.”

Nearly 95,000 people in the U.S. are currently waiting for kidney transplants, most suffering progressive health deterioration. For some groups, including patients over 60, death is a greater certainty than a transplant.

Given this significant public health problem, the U.S. Department of Health and Human Services set a goal of doubling the number of kidneys available for transplantation by 2030 as part of the Advancing American Kidney Health Initiative. One promising pathway toward that target is reducing the discard of viable human kidneys that now occurs, particularly from deceased individuals with hepatitis C virus infection. The number of those organs has soared over the past five years as a result of mounting deaths from the national opioid epidemic.

The MGH prospective trial is the first multi-center investigation to show the feasibility of donor positive to donor negative transplantation. Known as MYTHIC (Multi-Center Study to Transplant Hepatitis-C Infected Kidneys), the study was conceived and carried out in collaboration with the Perelman School of Medicine at the University of Pennsylvania. Each of the trial’s 30 kidney recipients at seven U.S. transplant centers was given an eight-week course of a coformulation of glecaprevir and pibrentasvir, powerful antiviral agents that target two distinct proteins within the virus that are essential to its survival.

While one patient died of complications of sepsis deemed unrelated to trial participation, no severe side effects or liver disease were observed in any patient, and allograft function at six months was excellent.

“Many of the patients showed a tiny amount of virus in their blood right after transplant, but that viral load became undetectable or unquantifiable in all recipients of HCV-viremic kidneys by four weeks of treatment, ” notes Raymond Chung, MD, investigator in the Liver Center and Gastrointestinal Division at MGH and co-senior author of the study.

The trial’s success extends to the development by the research team of an evidence-based clinical protocol for transplanting hepatitis C-infected kidneys that could be used by transplant centers anywhere, adds Chung.

“We sought to replace the many homegrown protocols based on varying treatment regimens with one that is sound, uniform and reproducible,” he explains. “We believe we have succeeded by creating a very simple approach that works in patients.”

Researchers are now hopeful that transplant centers will take notice of these encouraging results and the opportunity they afford to increase access to high quality organs by patients in critical need of a kidney transplant.

“By showing that these procedures are effective,” says Sise, “we’re hoping that insurance companies will also see the enormous benefit of making transplants with hepatitis-C infected kidneys uniformly covered and reimbursable. The ultimate goal of everyone should be to increase the quality and quantity of life for patients waiting for a kidney transplant.”

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