Donor lungs with hepatitis C safely transplanted to patients at UHN

Donor lungs from individuals infected with hepatitis C have been successfully transplanted into 10 patients at Toronto General Hospital (TG), University Health Network (UHN).

All patients have recovered from their transplant surgery. Eight of them have already tested negative for the virus and the last two patients have recently started taking the drug regimen.

The transplants are part of a clinical trial that is the first to assess the safety of transplanting hepatitis positive organs to non-infected patients using the ex vivo technology. Developed at TG in 2008, the Toronto Ex Vivo Lung Perfusion System (EVLP) perfuses organs outside of the body, allowing doctors to assess the organ and predict how well it will do before transplantation.

The use of hepatitis C infected organs to help deal with the shortage in organ donors will be discussed by experts at the Global Hepatitis Summit, which starts in Toronto on June 14.

“With the opioids crisis and persistent high rates of intravenous drug use, we have a great number of potential lung donors who are hepatitis C positive – many of whom didn’t even know they were sick when they were alive,” says Dr. Marcelo Cypel, thoracic surgeon at TG, UHN, scientist at Toronto General Hospital Research Institute (TGRI) and principal investigator in the study.

“The current protocol is to not use these organs, but we started to question if that still made sense in an era when direct anti-viral agents (DAAs) can cure hepatitis C,” he says.

The study is led by Drs. Cypel, Atul Humar, Medical Director of UHN Transplant, and Jordan Feld, specialist from the Toronto Centre for Liver Disease, TG, UHN.

Dr. Marcelo Cypel estimates there could be 1,000 more lungs available for transplant every year in North America by using hepatitis C positive organs (Photo: UHN)

In recent years, the latest drug regimen of sofosbuvir-velpatasvir for a 12-week period has been used to cure patients with hepatitis C around the world. However, there were still concerns around how this could impact transplants.

The questions researchers want to answer are: if hepatitis C negative patients can be safely transplanted with infected donor organs, and whether they can clear the virus after their surgery.

For this study, lungs were placed in the EVLP circuit in a sterile dome for six hours. The surgical team was able to evaluate the lung function and be certain that the organs were suitable for transplant, despite being infected with hepatitis C.

After six hours, EVLP reduced the hepatitis C virus count to very low levels. As expected, patients still contracted the disease. However, they tested negative for hepatitis within only three weeks of treatment with DAAs, in average.

Developed at UHN, the Toronto Ex Vivo Lung Perfusion System (EVLP) perfuses organs outside of the body. (Photo: UHN)

“This is an initial study, but it shows positive results,” says Dr. Feld. “It suggests that it is safe to use these organs which otherwise we could not have used. This could eventually be a big boost for organ donation.”

“We have a long standing tradition of excellence and pushing boundaries in transplant research and we are pleased that we were able to pioneer this study,” Dr. Humar says.

Dr. Cypel estimates that accepting hepatitis C positive donors would increase the number of lungs available for transplant by 1,000 per year in North America. Currently, approximately 2,600 lung transplants are done per year in Canada and the United States combined.

As of 2016, there were more than 240 patients waiting for a lung transplant in Canada alone and the estimate is that 20 per cent of patients die while waiting for lungs to become available.

Patient experience

As important as the fight against the virus, is the fight against stigma. As studies start to show that it is safe to transplant organs from hepatitis C positive donors, doctors are educating patients about the disease and on how effective DAAs are in curing it.

Stanley De Freitas, 73, is one of the patients who received lungs as part of the study. He suffered from pulmonary fibrosis and agreed to receive hepatitis positive lungs in October, 2017.

“People take breathing for granted and don’t realize the limitations of having a pulmonary disease,” says De Freitas.

“Now, every breath I take I think of my donor and it doesn’t matter that the donor had hepatitis C. I didn’t even have any symptoms of the disease. I recovered well and now I can enjoy life with my two daughters, four grandchildren and my two great-grandchildren.”

De Freitas says at first he was worried about contracting hepatitis C, but after receiving information about the disease, he didn’t think twice and gladly accepted the life-saving lung transplant. He urges other patients to do the same.

“If these lungs or other organs are available, go for it! The treatment is effective and you will have your life back.”

Eva Runciman, 52, suffered from Chronic Obstructive Pulmonary Disease (COPD). Before her transplant, in February, she couldn’t walk because she had difficulty breathing.

“I would tell everyone waiting for a transplant not to be afraid of accepting organs with hepatitis C, trust the treatment,” she says. “The change in life quality is just amazing. I now can walk, I can drive and play with my grandkids.”

(Photo: UHN)

About the clinical trial

The first phase of the study was comprised of the 10 surgeries – performed between October, 2017 and May, 2018. The average age of the organ donors was 33 and the average age of the recipients was 64. The study will be followed by a second phase that will further assess techniques to use organs carrying the virus.

This work is supported by the Canadian Institutes of Health Research, Medicine by Design, Toronto General & Western Hospital Foundation, Gilead Sciences and Xvivo Perfusion. Dr. Cypel also praised the efforts and support of Trillium Gift of Life, which co-ordinates organ and tissue donation across Ontario and without whom this trial would not have been possible.

“We are very grateful to our donors and to Trillium for coordinating the organ donor lists and making it possible for us to conduct this study.”

The Global Hepatitis Summit, 2018 is being held at Metro Toronto Convention Centre from June 14 to 17.

“The advent of DAAs has really created a dramatic shift in how we treat hepatitis C. This study is a perfect example of the latest developments in this exciting rapidly moving field that we will be discussing during this week’s Global Hepatitis Summit,” says Dr. Feld.

The summit will bring together top clinicians and researchers from around the world to Toronto to discuss the remarkable therapeutic developments in recent years and the prospect of disease elimination. The Global Hepatitis Summit 2018 is chaired by UHN’s physicians and researchers Drs. Harry Janssen, Jordan Feld and Adam Gehring.

 

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University Health Network is one of Ontario’s 23 research hospitals that contribute to a healthier, wealthier, smarter province. Look for other RESEARCH SPOTLIGHT posts on our Healthier, Wealthier, Smarter blog or join the conversation about why health research matters for Ontario on Twitter, using the hashtag #onHWS.

 

 

Health & Community Leaders Talk: Peter Pisters

Safer, Smarter Care for a Healthier Ontario

Peter Pisters, President and CEO of University Health Network, shares the value of research evidence in improving patient safety, generating smarter care and a healthier Ontario.

 Peter Pisters, CEO of University Health Network

Almost every person who works in health care has seen or heard about a terrifying event where a patient was hurt or was almost hurt because something went wrong.  Nobody who works in health care wants errors to happen.  Trust has been placed in us and we do everything we can to live up to that trust.

Notwithstanding the noble intentions of health care workers, preventable harm does happen and these events occur far more often than industry insiders or the general public understand.   Indeed, by our estimates – and there isn’t reliable data in Canada so we must extrapolate from U.S. data – more than 30,000 Canadians die each year as a result of preventable harm in health care settings.

The causes are many and familiar – wrong medication or medication given in the wrong dose, an infection acquired in the hospital because proper protocols for handwashing or sterilization of equipment are not followed, complications which arise from a fall that could have been prevented, foreign objects accidentally being left inside patients during surgery.  The list of types of preventable harm is a very long one and, in complex, dynamic environments that have high reliance on technology and where patients move from one setting to another being handed off to different care teams, the opportunities for errors grow.

I’m proud to be the leader of Canada’s most research-intensive hospital, where we apply research findings into improving clinical care and outcomes.  I see wonderful care and a commitment from everyone to heal and help our patients.  I also see the enormous possibilities of using our clinical teams and researchers to help us understand how errors occur and how we can make our hospital a much safer place to receive care.  Our efforts, in partnership with the Hospital for Sick Children, are going forward under a shared program that we call Caring Safely. Many other organizations including Sinai Health System, Women’s College Hospital, Health Quality Ontario, the Canadian Medical Protective Association, the Ontario Hospital Association and others have all expressed great interest in our efforts to drive preventable harm to zero. Through smarter, safer care, University Health Network, along with its partners, will help to build a healthier Ontario.

For critical insights on improving safety, we are looking to other industries that have made extraordinary safety improvements over the past 30 years.  These industries include aviation, nuclear power, and chemical manufacturing — industries that have a relative complexity of the work environment similar to healthcare and where reliability and resilience have been hard wired into the workforce. Collectively, these industries have adopted practices known as high reliability. In high reliability industries safety is a core value and employees are supported and trained to spot problems before they happen and take immediate action. The lessons learned from success in other industries are applicable to healthcare.

I believe that safety is an implicit expectation that Ontarians have of our hospitals. For those who would like to read more about High Reliability Organizations I recommend two books – Why Hospitals Should Fly by J.D. Nance and Managing the Unexpected by Karl Weick and Karen Sutcliffe of the University of Michigan. The first is written in novel form and imagines what it would be like to work in a hospital that has adopted the principles of reliability and resilience.  The second book is a seminal academic work that outlines the principles that define high reliability organizations.

At UHN, we started this journey with an organization-wide survey from the Agency for Healthcare Research and Quality (AHRQ) that has given us rich data about attitudes to safety on our units, in our clinics and throughout the organization.  The response was overwhelming with two of our sites achieving 100% participation, and a third at 98%.  This extraordinary response to administrative efforts to measure our safety culture clearly demonstrates the deep interest that the UHN community has in our safety transformation and our shared commitment to safety for each other and for the patients we serve.  One major benefit of the AHRQ safety survey is that it is used throughout North America, enabling us to benchmark ourselves with over 700 hospitals.

You can learn more about the work Canada is doing to address patient safety here.

Toronto Rehabilitation Institute has been using the AHRQ safety culture survey for many years and has used their data to identify issues that can then be worked on by the manager and the team on the unit.  They have seen changes to their safety culture year over year and all of UHN will learn from their experience with the survey and with the ways they have worked with their staff to make Toronto Rehab a safer organization.

The Institute of Medicine once noted that “errors… are costly in terms of loss of trust in the health care system by patients and diminished satisfaction by both patients and health professionals”. By decreasing incidents of preventable harm and increasing a focus on patient safety we can create a healthier and smarter environment for everyone that comes through our doors.

UHN is a proud member of CAHO, which supports the health research enterprise that makes Ontario Healthier, Wealthier and Smarter.  We’re determined to also make it safer, and I thank CAHO for allowing me to write about the start of this journey and welcome your thoughts and questions.

 

Read more Health and Community Leaders Talk posts here, and share your own insights about the value of health research on Twitter with our hashtag, #onHWS.

To learn more about how health research makes Ontario healthier, wealthier, and smarter, check out our website and our other blog posts and videos.