Transplant innovations give more patients second chances

Some of the first patients Sukru Emre, M.D., evaluated for transplant after his arrival in New Haven had already been rejected for surgery at Yale, including an 8-month-old girl who weighed only 2 kilograms. Her size made a liver transplant—a highly complex procedure under the best of circumstances—extremely problematic. Emre chose to operate. Today that tiny baby is a healthy 4-year-old.

Emre, section chief of transplantation and immunology, came to Yale three years ago to revitalize transplant surgery. A surgeon of international reputation, Emre was expected to expand Yale’s program as he’d grown Mount Sinai’s in New York. In his first two and a half years in New Haven, 110 liver and 270 kidney transplants were performed at Yale with best-in-the-nation outcomes for both pediatric and adult patients. The transplant program, which hired its fourth surgeon this past summer, now has a patient volume that equals those of larger centers.

The Yale-New Haven Transplantation Center is also expanding the realm of cases in which success is possible. Because donor organs are precious resources, they are given to people most likely to benefit from them. As a result, patients with multiple health issues are often denied organs. The transplant center, however, has developed innovations that turn poor candidates into success stories. Frequently, patients with such complicating factors as multiple diseases or previous surgeries seek liver transplants at Yale after they’ve been rejected elsewhere. “When I say that I could do the surgery, life comes back into their eyes,” says Emre.

One complication that often leads to rejection for transplant is HIV-positive serostatus. Yale’s is one of the few programs that can work with both HIV-positive donors and recipients. “HIV is a controllable disease,” explains Emre. As life expectancy for HIV-positive patients increases, transplant surgery becomes more feasible. These patients can use organs from living donors who are also HIV-positive. (Positive donors, however, cannot give their organs to HIV-negative recipients.) Working with AIDS specialists, the transplant team can fine-tune a compatible mixture of HIV medications and anti-rejection drugs necessary for transplant surgery. The center did its first positive-to-positive liver transplant earlier this year. The operation was a success.

Last summer Yale began offering hepatocyte transplants for newborns with a metabolic disease called “urea-cycle defect,” which causes hyperammonemia. These infants lack an enzyme involved in the production of urea, allowing ammonia to build up in their bloodstream and cause toxicity that leads to brain damage. Hepatocytes harvested from discarded sections of donated livers can help correct this metabolic defect, thus lowering the dangerous ammonia levels. The primary aim of the therapy is to prevent brain damage—but there are also long-term implications. Many of these young patients will have liver transplants in their futures, but the damage they incur in infancy can make them poor prospects. Since it is hard to find size-matched whole small pediatric liver donors, split and living donor liver transplantation techniques are the only way to perform transplant operations in newborns and infants. In living donor transplantation, a small part of a liver is taken from a living donor. In split liver transplantation a deceased donor liver is cut into two pieces; the larger piece is used for transplanting an adult patient, and the smaller piece is used for a pediatric recipient. Emre said that addressing the hyperammonemia immediately by using hepatocyte transplantation could make these infants excellent candidates for living donor or split-liver transplants later or even provide sufficient metabolic improvement that transplantation could be avoided. Emre also wants to develop a research project to determine whether the therapy can be applicable to adults with chronic liver disease and acute liver failure.

The procedure requires leading-edge lab work to support it, including tissue typing. Citing the importance of partnerships with basic scientists, Emre is working closely with the Human and Translational Immunology group to recruit a leader in translational research in transplantation.

Emre’s research lab is also working on many animal research projects. The aim is to bring clinical problems in the lab for study. “Once we have reliable solutions in the lab, these developments will be transitioned to improve patients’ outcomes,” Emre said. The center is also advancing surgical techniques as Emre and his colleagues refine transplant procedures on animal models.

Emre has also developed a core to advance care and research in acute liver failure. With dedicated intensive care unit beds at Yale-New Haven Hospital, patients in acute liver failure can be transferred “in a split second,” said Emre. Patients are cooled to slow their metabolism and decrease brain damage. They are put on a molecular adsorbent recirculating system, or MARS—a technology similar to dialysis that detoxifies the liver and kidney simultaneously. Since the program’s establishment this year, 15 patients have been admitted in this dangerous state. All survived until a donor liver became available or recovered enough liver function that transplant surgery was no longer necessary.

Since Emre’s arrival, Yale has addressed the national shortage of donated organs with live-donor liver transplants. The ancient Greeks were on to something with the myth of Prometheus, sentenced to have his liver eaten by an eagle for giving human beings the secret of fire. Each day the organ grew back so that the fire-stealing Titan endured angry Zeus’ punishment anew. As it happens, the human liver does regenerate—a living donor can offer a section of his or her liver for transplantation.

The Yale center is developing programs to safeguard the health of these donors and improve their overall experience. Donors come in healthy and pain-free but frequently experience wound and back pain after the surgery, explained Emre. They need to be counseled about what to expect and given as much pain relief as possible. An education center provides articles about the procedure and videos of the surgery. After the part of liver is harvested, the donor will spend two days in intensive care with a dedicated nurse. Donors are then given a private room after discharge from the ICU. Throughout the process a donor advocacy team—a social worker, a nurse, and a physician—will participate in care with the surgical team. Each patient will be visited in the hospital by a psychologist, and donors are also offered such alternative therapies as Reiki, reflexology, massage, and acupuncture. The center is studying the impact of these interventions on the donors’ quality of life.

“We see patients as not only a body, a liver, or a kidney. We see them as a soul as well,” said Emre.