With only months to live, Peter Bucciarelli was in desperate need of a double-lung transplant. When he heard about a new trial at the Brigham that would possibly increase his chances of receiving donor organs sooner, the 56-year-old patient didn’t think twice about enrolling.

This summer, he celebrates two years post-transplant. Bucciarelli is one of 35 patients who are thriving after participating in the DONATE HCV Trial, which studied whether thoracic organs (heart or lung) from donors infected with hepatitis C could be safely transplanted to recipients who did not have the virus. A multidisciplinary team of experts found they could successfully transplant the organs and then block the virus from replicating.

In a paper published in The New England Journal of Medicine earlier this week, the DONATE HCV Trial team describes a four-week antiviral treatment regimen started within hours of organ transplantation that prevented hepatitis C virus (HCV) infection in all patients, expanding the pool of eligible heart and lung donor organs. This is the largest clinical trial to date for HCV thoracic organ transplantation.

“There was a 100 percent success rate in terms of HCV treatment and six-month graft survival,” said corresponding author Ann Woolley, MD, MPH, of the Division of Infectious Diseases. “Direct-acting antivirals have revolutionized the field of hepatitis C treatment and have also created an opportunity to transplant organs from hepatitis C-positive donors.”

While transplants from these donors have been performed before, Woolley said the best approach to doing this — including when to initiate antiviral treatment, how long to treat patients after transplant and outcomes for heart and lung transplants — has not previously been systematically studied.

The Right Decision

From left: Ann Woolley and Peter Bucciarelli

Bucciarelli, a former contractor, said when his care team spoke with him about the trial, he knew it was the right decision to enroll.

“I was only given two months to live at the time,” said Bucciarelli, who was diagnosed with emphysema in 2010. “Being a part of this trial expedited things for me and ultimately saved my life.”

Since receiving his lung transplant, Bucciarelli has remained close with his care team, including Woolley, and often makes the four-hour drive from his home to the Brigham for routine checkups. He said he feels great and is thrilled to get back to living his life.

“I was able to see my daughter get engaged, and my son made me a grandfather for the first time,” Bucciarelli said. “Those are the moments I live for.”

Encouraging Results

In their paper, researchers presented data on patients who had enrolled in the study by February 2018. Six months or more after transplant surgery, all had undetectable amounts of hepatitis C and functioning transplanted organs. The team has enrolled 69 participants to date.

Nearly all patients who received organs from HCV-positive donors had evidence of the virus immediately after transplantation. However, very early, preemptive treatment prevented it from establishing an infection. All recipients cleared the virus within about two weeks, and it remained undetectable thereafter.

“It was critically important to us to determine this treatment not only prevented transmission of hepatitis C but also didn’t worsen outcomes for our transplant patients,” said co-author Steve Singh, MD, former surgical director of the Heart Transplantation and Mechanical Circulatory Support in the Department of Cardiac Surgery.

Although organ transplants in the U.S. have increased over the last five years, an estimated 1,000 patients die annually waiting for a lung or heart transplant. Drug intoxication deaths have led to a rise in available organs for transplantation, but donor hepatitis C infection has been a leading reason that otherwise medically suitable organs are deemed ineligible for transplantation.

“HCV infection has been a long-standing reason to decline donation of suitable organs,” said co-author Lindsey Baden, MD, director of Clinical Research in Infectious Diseases. “Transmission does occur, but a short, four week course of antiviral therapy led to rapid HCV clearance. These data demonstrate how preemptive therapy can stop transmission, thus decreasing medication burden, drug interactions and cost.”

The team also analyzed safety outcomes, finding that there were no hepatitis C-attributable adverse events.

“This study provided a unique opportunity to explore the utilization of thoracic organs from hepatitis C positive donors for transplantation, which to date have been underutilized despite being relatively common in the current donor population,” said co-author Hilary Goldberg, MD, MPH, medical director of the Lung Transplant Program. “This may allow us to provide successful transplantation to many recipients who might otherwise never have access to it.”