Banner by Sumana Kethu
The Gift of Life: Organ Donation
By Maddie Verhagen
“If I hadn’t gotten a transplant within the next few months, there was no way I could have made it much longer,” says Erin O'Sullivan, who was 16 at the time of her liver transplant, almost six years ago. Erin, a Rochester, New York native, full-time college student, and my long-time friend, was diagnosed with primary sclerosing cholangitis (PSC) at just nine years old. PSC is a chronic liver disease that can lead to extreme damage and scarring of the liver due to the blockage of bile ducts. In some cases, PSC can lead to liver failure, in which transplantation is the only treatment option.
At just fourteen years old, Erin was confronted with the fact that she would eventually need a liver transplant.
“They offered me to either go to Pittsburgh or Boston. After I visited Pitt, I just knew that that’s where I wanted it to be.”
Her current status did not meet the criteria to be put on the transplant list, but six months later, Erin traveled to UPMC Children’s Hospital of Pittsburgh for a routine check-up and doctors discovered that she had developed hepatopulmonary syndrome (HPS). This disorder, which can be fatal, is caused by advanced liver disease. It results in enlarged blood vessels in the lungs, making it difficult for red blood cells to take in oxygen.
Erin was immediately placed at the second spot on the liver transplant list and the waiting game began. Her health began to decline after battling with HPS due to liver disease.
“I started to get a lot of infections in my liver. I had to get a PICC [peripherally inserted central catheter] line and do infusions four times a day.”
After being on oxygen for a year and a half, eagerly waiting for the life-changing phone call, Erin finally received the news that they had a liver for her in March of 2018. Livers are viable for only 12 to 18 hours after they are recovered from the deceased donor; however, the donor had not been taken off life support yet, so Erin was able to spend one last night with her family at home before her four-month stay in Pittsburgh. The next morning, Erin headed for UPMC Children’s Hospital with her family. On March 13th, she underwent the 11-hour surgery.
Erin’s transplant was unlike most liver transplants. The procedure involved three patients: a cadaveric donor, a living donor/recipient, and a recipient. This rare process, called a domino transplant, is used to increase the donor pool and allow for more people to receive a life-saving transplant. A deceased donor’s liver was given to a young man who had maple syrup urine disease (MSUD), a metabolic disorder characterized by the absence of an enzyme that breaks down certain amino acids. Without this enzyme, harmful substances build up within the body. To cure his MSUD, the young man received a liver that had the enzyme he lacked. Since Erin could produce the missing enzyme, she was able to take the young man’s liver, as it was otherwise fully functioning.
After the arduous procedure, Erin would still have a long journey ahead of her. Following a transplant, many complications can arise. Our immune systems are masters at recognizing self vs. non-self. Although cross-matching is used to obtain optimal compatibility between the organ donor and recipient, allograft rejection risks remain. To prevent the immune system from attacking the allograft, transplant patients are administered immunosuppressant drugs that inhibit the overactivity of the immune system. However, due to this immunosuppression, transplant recipients are more susceptible to developing chronic infections. Disruptions to the fine balance of the immune system following a transplant have the potential to induce a spectrum of life-threatening complications, one of the most severe being post-transplant lymphoproliferative disorder (PTLD).
The risk of developing PTLD is greatest within one year after the transplant and depends on the type of transplant—with heart transplants at the highest risk. For adults, developing this disorder is rare; only 2 to 4% of liver transplant recipients will develop PTLD within one year of the transplant. However, up to 20% of pediatric liver transplant recipients will develop PTLD in this same period.
One reason why pediatric transplant recipients may see an increased incidence of PTLD is due to the Epstein-Barr Virus (EBV). This human herpesvirus, transmitted via saliva, is present in 95% of the adult population. Upon primary infection, generally, during adolescence, most immunocompetent individuals will seroconvert, and develop antibodies, asymptomatically, but a portion will develop acute infectious mononucleosis, more commonly known as mono or the kissing disease. For these individuals, mono is the most severe EBV complication they will face. However, for immunocompromised individuals, such as transplant recipients, exposure to the usually harmless virus can pose a multitude of threats. At the time of Erin’s transplant, her serostatus for EBV was negative, but the donor was EBV-positive, meaning she would have to battle primary EBV infection at the time of her transplant. This is the case for many pediatric transplant recipients. Primary EBV infection coupled with immunosuppression can be a recipe for disaster, which is one reason higher percentages of PTLD are observed in pediatric transplant recipients compared to adults. Because of this, Erin struggled with rejection around a month post-operation.
“I started to feel really sick…I went in for my routine labs and they were like, ‘Oh my god you’re going into major rejection.’”
Erin was put on various steroids to prevent her immune system from attacking the allograft. Luckily, she was able to overcome the spike of rejection and primary EBV infection without developing PTLD.
Dr. Diana Metes, Professor of Surgery and Immunology at the University of Pittsburgh, conducts translational research on the human immune system. Some of her recent projects have reached the clinical trial stages. One of her current projects is investigating the immune responses of pediatric transplant recipients to further understand the underlying mechanisms of allograft rejection in the scope of EBV infection.
“Pediatric patients can develop cancer, lymphoma, due to the effect of a latent viral infection that all of us have, but doesn’t pose a problem in immunocompetent humans,” describes Metes. “The clinical observation was that not all patients have the same risk. It looks like patients that were EBV-negative at the time of the transplant that don’t have memory and haven’t seen the virus and had to develop a potent immune response,” were at a higher risk.
Memory is a characteristic of some immune system cells that can remember specific antigens by equipping themselves with the necessary mechanisms to eliminate a pathogen swiftly if it were to infect the host again. If Erin’s EBV infection had persisted, her risk for developing PTLD would have increased, resulting in the loss of the allograft or her life. Dr. Metes’s discoveries within this field have the potential to decrease rejection rates for pediatric transplant recipients.
For the first two years following her transplant, Erin was in and out of the hospital for small infections and complications, but luckily avoided another spike of rejection. Now 22 and approaching the six-year mark since her transplant, Erin lives a healthy life taking little medication and undergoing blood tests from time to time. She is able to attend concerts, go to school, and hang out with friends and family—all experiences she missed out on while she was in and out of the hospital. When speaking about her experience, she expresses, “I feel like it has shaped what I want to do with my career.” Erin is now pursuing her degree in social work, intending to work in a hospital setting with pediatrics. She hopes to provide pediatric transplant recipients with the same support and positive experiences she had during her transplant.
More than 103,000 people are on the national transplant waiting list right now and a new name is added every 8 minutes. One person’s organs and tissues can save up to 8 lives and enhance 75 others. Passing on the organs that enabled you to live life to its entirety opens doors for people like Erin to embrace life to its fullest.