SEATTLE — Since islet allograft transplantation for diabetes is still not very successful over the long term, it may be time to reconsider using the liver as the location for infusing the transplant cells, Dr. R. Paul Robertson said at the annual meeting of the American Association of Clinical Endocrinologists.
“They should be getting out of the liver,” he said. “There is just no reason to attack the liver like that.”
When the group from the University of Alberta, Edmonton, first published its islet transplantation results in 2000, researchers reported good success with the liver as the transplantation site; 100% of the patients were insulin free out to 1 year post procedure, said Dr. Robertson, a professor of medicine and pharmacology at the University of Washington, Seattle, who has done metabolic studies on transplant recipients.
But now with reports of patients out to 5 years, it seems that majority of the Edmonton group's transplantations did not last. The median duration of function of an islet transplant appears to be about 15 months. Of 65 patients reported on in 2005 by the group, 15% had failed, 77% had returned to insulin therapy, and only 8% remained completely insulin free, Dr. Robertson noted (Diabetes 2005;54:2060–9).
Moreover, while centers such as the University of Miami, the University of Minnesota, and the University of Pennsylvania have done successful islet transplants, at least three other places have had no success, including the University of Washington, Dr. Robertson said.
The problem may be the liver, he said. The liver is the repository for the transplant drugs used to prevent rejection—which may be toxic to the islets—as well as for all the other environmental toxins.
In addition, use of the liver was thought to have the advantage of being physiologically appropriate, because the pancreas dumps insulin through the liver. It also was considered a safe procedure, because the cells are simply infused into the hepatic portal vein, where they are then washed into the organ.
But canine experiments suggest that the islets may not function optimally in the liver. And there have been serious adverse events reported with the procedure. According to one report, 41% of patients transplanted in Edmonton had complications that required hospitalization, Dr. Robertson said.
Other experiments have investigated infusing the islets into the intraperitoneal space, subcutaneously, and next to the kidney. “We need to be patient and support this kind of research,” Dr. Robertson said.