Smoking cigarettes and working in the paint and drywall business for 35 years silently wreaked havoc on Pete Bucciarelli’s lungs. He didn’t learn how sick he was until 2010, after he collapsed suddenly on his living room floor.
Doctors told him he had severe emphysema, and despite surgery and other treatments, his condition deteriorated. He soon needed an oxygen tank. Cleaning his house became too taxing, nor could he go grocery shopping — a whiff of someone’s perfume or cologne made it hard to breathe. By 2017, he was on the lung transplant list.
“They told me I only had a couple months to live,” said the 56-year-old from Bethlehem, N.H. For patients like Bucciarelli, the median wait for a lung transplant is nearly 13 months, and 40% wait longer than two years. But he was offered a faster option — accepting lungs from a donor infected with the hepatitis C virus, as part of a clinical trial testing a way to dramatically expand the pool of organ donors.
The results of that study, reported Wednesday, suggest that lungs, as well as hearts, can be safely transplanted from virus-infected donors. A four-week course of antiviral drugs prevented all the recipients from being infected, and those followed for at least six months were doing well and remained uninfected.
The trial, published in the New England Journal of Medicine, is the largest to examine the safety of using infected lungs and hearts. The researchers, led by Dr. Ann Woolley of Brigham and Women’s Hospital, estimated that using organs from donors infected with hepatitis C could increase the supply of hearts and lungs by at least 25 percent.
In the United States, there are currently 5,226 patients waiting on the heart or lung transplant list. There is a perpetual shortage of organs available for donation, and it is estimated that about 1,000 patients die each year waiting for a new heart or lung. Many organs, including hearts and lungs, are discarded if there is evidence or suspicion the donor was infected with hepatitis C virus (HCV), which is the most common chronic blood-borne infection in the United States and one most often spread through intravenous drug use.
In many areas of the country, nearly one-third of donor organs now come from IV drug users, according to an editorial published in the journal — many of them victims of the nation’s opioid crisis. “At least in the short term,” transplants from HCV-positive donors into uninfected recipients is “a very promising way to get people transplanted faster and expand the donor pool,” Dr. Emily Blumberg, the author of the editorial and a professor of medicine at the Hospital of the University of Pennsylvania, told STAT.
In the past, transplants from HCV-positive donors were associated with high rates of transmission of the virus to the recipient and increased mortality. The standard of care was to only use these organs for high-risk patients looking for a last resort or to not use them at all. However, the arrival in 2014 of a new class of drugs targeting hepatitis C brought about a sea change. These drugs are well-tolerated, easy to take, and have high cure rates for chronic HCV infections — though they’re also very expensive.
This revolutionary change in HCV management was the foundation of the Brigham and Women’s trial protocol. Researchers began enrolling patients in March 2017. Donors and recipients were screened by the same standard criteria for heart and lung transplantation, with the exception that donors were not disqualified if they had active or past HCV infections. Antiviral treatment was started within hours of transplant surgery, and patients were maintained on these medications for four weeks.
Bucciarelli was one of the first patients in the trial and said he got a call that a match had been made on July 4, 2017, only two months after enrolling. “I’m going to go for it,” he recalled telling a friend. “Why wouldn’t you do it?” the friend replied.
Five days after his transplant,, he was told he had no traces of HCV in his blood. Since then, he has enjoyed two years without carrying oxygen with him and has slowly recovered to his normal baseline functioning.
“I would recommend that drug as highly as possible,” he said during an interview this week, while visiting the Brigham for a checkup. “It opens up so many opportunities for people.”
Brigham researchers reported on a total of 44 patients who underwent a HCV-positive heart or lung transplant. Thirty-five of them (28 lung recipients and seven hearts) had at least six months of follow-up, including 16 followed for a year. Immediately after transplantation, all recipients had hepatitis C viral loads in their bloodstream that was proportional to the viral loads of the donors. Most of the patients were able to clear the infection after a couple days of taking the antiviral medications, and all had undetectable viral loads after two weeks of therapy.
There were more cases of organ rejection in the lung transplant patients than seen in a comparison group who received uninfected lungs during the same time period, but the researchers said this increase was not statistically significant after accounting for possible confounding differences between the groups.
The trial protocol has several benefits over the ones used in earlier studies, the researchers reported. Because the medications are active against all strains of HCV, treatment could be initiated right away, without the delay that would be incurred by having to test the strain of HCV in the donor. The team also preemptively treated recipients without waiting for them to develop signs of infection. The belief is that this prevents the patient from being infected in the first place and avoids infectious and non-infectious complications.
Finally, the medication regimen contrasted with the typical 12-week regimen. This dramatically cuts down on costs and the pill burden for patients. Woolley said that since evidence suggests that the patients in the trial cleared the virus quicker than four weeks, future studies may involve an even shorter duration of treatment.
Similar results have been published by researchers at Vanderbilt University Medical Center and the Hospital of the University of Pennsylvania, who studied HCV positive heart transplants. Blumberg, one of the investigators in the Penn trial, said all 10 patients who received heart transplants from HCV-positive donors in that study were able to clear the infection after 12 to 16 weeks of anti-viral therapy.
Blumberg cautioned that these protocols are still in the research phase and require careful monitoring and investigation before they are widely used. There are still many unanswered questions regarding the dosage and duration of antiviral drugs, the costs of treatment, the applicability to all subpopulations of patients, and what are the best plans for long-term follow up.
“We don’t have long-term outcomes,” she said. “We don’t know if 5, 10, or 20 years down the line [these drugs] will still work. … There are a lot of things about hepatitis C that we are just starting to appreciate.”
In the editorial, Blumberg raised additional reservations about the Brigham findings: Organ donors were “surprisingly young,” and HCV-positive ones were younger than the uninfected donors. The recipients of infected organs were also less critically ill than the typical heart or lung transplant patient. “Nevertheless, this article clearly provides support for further consideration of the use of organs from HCV-infected donors,” Blumberg wrote.
Previously, the topic of using HCV-positive organs for transplantation was met with skepticism and reluctance by those in the transplant field. But Woolley said she is optimistic that recent trials — not just with heart and lung transplant patients, but also those receiving kidneys and livers — will catalyze a paradigm shift in the care of transplant patients. “We hope the transplant community will adopt this, and it could lead to changes in policy,” she added.
Bucciarelli is similarly upbeat, and is planning a trip to Italy. Rather than having a life expectancy counted in months, he said he now looks forward to years of spending time with his new grandchild, and riding his Harley motorcycle.
Our non government organization has worked with several patients from both of these prestigious universities. Sorry for being vague, we have to be, we are Americans helping physicians from major universities have access to hepatitis C treatments from India. If you have been denied hep C treatment like so many Americans, send an email to us or give us SunnyPharma.info a call at 858-952-1077. So many of the doctors mentioned here are amazing people. Keep up the good work.
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