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Ira Fox, MD, is a transplant surgeon who has spent much of his career seeking alternatives to transplantation for patients with life-threatening liver diseases.
The development of liver transplantation in the 1980s transformed the treatment of liver diseases, providing a life-saving option for many patients, Dr. Fox recalls. But, while liver transplantation techniques have been markedly refined over the past 30 years, a significant number of patients who undergo liver transplants still develop severe complications or experience rejection of the transplanted organ. Moreover, the number of patients who would benefit from a liver transplant exceeds the available supply of donor organs.
For the past 20 years, Dr. Fox has been working on hepatocyte (liver cell) transplantation, which offers the promise of a less invasive alternative to liver transplantation for some patients.
“In hepatocyte transplantation, instead of replacing the entire liver, we isolate liver cells and infuse them into the patient’s existing liver,” he explains. Children’s Hospital of Pittsburgh is one of the first places in the world to perform this novel and still experimental procedure.
After earning his medical degree at Columbia University, Dr. Fox completed residencies in surgery at the University of California Medical Center, San Francisco, and New England Deaconess Hospital, Boston, followed by a fellowship in immunology at Harvard Medical School. In 1985 he came to the University of Pittsburgh School of Medicine for postgraduate training in transplantation under world-renowned organ transplantation pioneer Thomas E. Starzl, MD, PhD.
Dr. Fox went on to become a professor of surgery and senior associate dean for research and development at the University of Nebraska College of Medicine. In 2008 he returned to Pittsburgh, where he now serves as director of the Center for Innovative Regenerative Therapies (a collaborative effort between Children's Hospital of Pittsburgh of UPMC and the University of Pittsburgh’s McGowan Institute for Regenerative Medicine), medical director of the McGowan Institute, and professor of surgery at the University of Pittsburgh School of Medicine.
Hepatocyte transplantation holds out particular promise as a potential alternative treatment for metabolic diseases affecting the liver such as Crigler-Najjar syndrome, phenylketonuria, and urea cycle disorders, which currently can be treated with a liver transplant. In all of these diseases, the underlying problem is a missing liver enzyme whose job is to help the body break down protein. As a result of this missing enzyme, toxins build up in the body, causing damage to organs including the brain.
“Many of these patients end up having liver transplants even though, except for one missing enzyme, their livers function perfectly well,” says Dr. Fox. “If, instead of replacing the entire liver, we could replace the defective cells, these patients could avoid liver transplants as well as many of the associated complications.
“The beauty of hepatocyte transplantation is that it can be performed while the patient is waiting for a liver transplant,” he continues. “If it’s successful, the patient won’t need a liver transplant, which frees up a donor liver for a patient on the waiting list who is not a candidate for hepatocyte transplantation. And if, unfortunately, the hepatocyte transplant doesn’t work, the patient still has the option to undergo a liver transplant.”
To date, fewer than 60 people in the world have received hepatocyte transplants. More research is needed to definitively show that hepatocyte transplantation can eliminate the eventual need for a liver transplant, says Dr. Fox. Children with life-threatening metabolic disorders affecting the liver may be eligible to enroll in a clinical trial of hepatocyte transplantation that Dr. Fox is conducting at Children’s Hospital.
In addition to his work on hepatocyte transplantation, Dr. Fox conducts research aimed at understanding why patients with liver cirrhosis (the most common condition requiring a liver transplant) develop liver failure. He is also involved in stem-cell research that could one day enable doctors to correct metabolic diseases inside patients’ own cells, making liver transplantation unnecessary.
At the Center for Rare Disease Therapy, says Dr. Fox, families will find empathetic doctors who have a great deal of experience with their child’s condition. “There is such a tremendous amount of expertise here,” he says. “This is where I would want to bring my own child for treatment if he or she had a rare disease.”
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