New transplant research aims to salvage infected donated organs
Retired subway and bus driver Stanley De Freitas had just celebrated his 70th birthday when he started coughing, tiring easily and feeling short of breath. He was diagnosed with pulmonary fibrosis, a severe scarring of the lungs, and put on the wait list for a transplant.
“Life became unbearable,” De Freitas, now 74, told Reuters by phone from his home in Toronto. “From the time I got up in the morning until when I went to bed at night, I struggled through every breath of air.”
After two years, De Freitas was offered a lung, with one significant downside: The donor had hepatitis C.
In October 2017, he became the first patient enrolled in a recently published study conducted at Toronto General Hospital testing a technique that aimed to flush out and inactivate the hepatitis C virus from donor lungs before a transplant.
The research comes amid a spike in available organs linked to the opioid overdose crisis, meaning many are contaminated by hepatitis C as the virus is commonly spread by sharing needles. Since it can easily infect an organ recipient, those organs are usually discarded despite the urgent need.
Data from the United Network for Organ Sharing (UNOS), which matches donors with recipients, shows that 97 percent of people waiting for a lung in the United States last year were unwilling to accept an organ from a donor who tested positive for hepatitis C.
While hepatitis C causes serious liver disease, the virus can be present in the blood in other organs.
Researchers are testing different approaches to salvage infected organs.
A study published in April showed that giving patients antiviral therapy just hours after transplant surgery can successfully attack the virus before it gains a foothold in the recipient.
Eliminating the virus prior to transplant would simplify the procedure for patients, said UNOS Chief Medical Officer David Klassen. It could also significantly cut down on wasted donor organs.
The technique used in Toronto, known as ex vivo lung perfusion, keeps organs “alive” outside the body by pumping them with a bloodless oxygenated liquid. They used ultraviolet C light to irradiate the solution, aiming to deactivate the hepatitis C virus and make it non-infectious.
Perfusion allows doctors to evaluate and potentially rehabilitate organs for transplant, and buys them more time than storage in ice boxes, which can cause tissue damage.
Toronto researchers used a solution from Sweden’s Xvivo Perfusion AB with the hospital’s own ex vivo lung perfusion system, a bubble-like machine made from off-the-shelf components and an intensive care ventilator.
The study of 22 patients, published in The Lancet Respiratory Medicine on Wednesday, had mixed results. Adding light therapy significantly decreased the amount of virus, but all but two of the patients contracted hepatitis C, which is now curable.
Infected patients, including De Freitas, were treated with a 12-week course of antiviral drugs that rendered the virus undetectable in all of them. Two of those patients relapsed but were retreated and cured. One patient in the study died due to complications from lung transplantation.
“All of the patients were in a very sick condition,” said Marcelo Cypel, surgical director at University Health Network in Toronto and co-author of The Lancet Respiratory Medicine study. “Perhaps some of them wouldn’t have made it to the transplant in time if they were not offered these type of organs.”
The researchers are planning another study combining perfusion with a photodynamic therapy, a type of light they believe could be more effective against the virus than ultraviolet because it can penetrate the organ as well as the solution.
In the United States alone, almost 113,000 people are on organ transplant lists, including more than 1,400 awaiting a new lung. Hundreds die each year while on the list or after becoming too sick to endure a transplant.
A tragic public health crisis has led to an unexpected opportunity. With the jump in deaths from opioids such as heroin and fentanyl, overdose victims now account for 13% of US organ donations, up from less than 4% a decade ago, according to UNOS.
Many of those organs are going to waste. For example, last year less than 4% of hepatitis C positive donors in the United States had lungs used for transplantation, the study’s authors said in the paper.
Other researchers are working with perfusion technology to improve the function of donated lungs, hearts and livers.
Scientists at the University of Oxford were able to improve the quality of 16 donated livers with signs of a fatty liver disease. They treated donated organs outside the body with drugs and captured fat that was washed out of the liver through a filter on a transportable perfusion device developed by Britain-based OrganOx, according to a study presented last year.
OrganOx has European Union clearance to use its device on livers and hopes to gain US approval by the end of 2020.
Perfusion device use currently is limited by cost, which can stretch to hundreds of thousands of dollars, and by lack of expertise and training.
De Freitas, though, is grateful the Toronto researchers are testing perfusion to salvage organs.
“Every day I get up and I thank the Lord, I thank the doctors because I am not supposed to be here,” he said. “I am supposed to be on the other side.” (Reuters)