WASHINGTON, D.C., April 30 – While matching currently is not used for liver transplantation, a study of more than 3,000 transplants suggests such testing for donor and recipient compatibility could reduce the incidence of disease recurrence after transplantation. The results of the University of Pittsburgh study – the largest study of its kind from a single institution – could help settle the score in a debate about the role of matching for liver transplantation, which has had tissue typers and surgeons on opposite sides of the issue for nearly two decades.
According to the retrospective study of 3,261 patients who received liver transplants at the University of Pittsburgh, immune system compatibility, or histocompatibility, between a donor and recipient not only has an impact on the incidence of rejection and graft failure, but disease recurrence after transplantation is profoundly affected as well. Their results were presented today at the American Transplant Congress, Transplant 2002, at the Marriott Wardman Park Hotel in Washington, D.C.
Specifically, the researchers found that while a match between donor and recipient indicates organ rejection is less likely, a match also increases the odds that patients transplanted for hepatitis C or primary biliary cirrhosis will have recurrence of their disease.
"This is particularly significant for hepatitis C, the most common indication for liver transplantation and where the absolute majority of the patients suffer recurrence after transplantation. Perhaps by paying attention to histocompatibility we may be able to reduce the numbers," noted John J. Fung, M.D., Ph.D., Thomas E. Starzl Professor of Transplantation Surgery at the University of Pittsburgh's Thomas E. Starzl Transplantation Institute.
Matching is considered important for kidney transplantation and has been performed routinely for years. But for liver transplantation, the practicality and merits of its use have often been questioned. Time restraints make the test impractical most of the time. But more importantly, most surgeons believe matching is irrelevant for transplants of the liver, an organ that is better equipped to mediate immune reactions against it. Hence, the test is not used to determine whether a donor liver is a good match for a particular recipient. Instead, surgeons pay closer attention to blood type compatibility and the size of the liver relative to the recipient.
Even so, researchers at the University of Pittsburgh have been collecting information about histocompatibility as part of an extensive database covering about 7,000 liver transplants performed at the center since 1981, representing the largest single-center experience in the world.
For the study on histocompatibility, researchers limited their analysis to 4,000 liver transplants in 3,261 patients: first-time liver transplants performed between February 1981 and March 2000 in adult recipients who did not receive additional organs.
Histocompatibility is determined by the degree of similarity between a donor's and recipient's profiles of human leukocyte antigens, or HLA. These are specific molecules found on cells that serve as signals to antibodies and other cells of the immune system. HLA testing yields information about matches or mismatches between specific HLA molecules.
Results of the study indicated that a match significantly decreases the incidence of acute and chronic rejection, reported Igor Dvorchik, Ph.D., director, section of biostatistics, Thomas E. Starzl Transplantation Institute, research assistant professor of surgery, University of Pittsburgh School of Medicine, and research assistant professor of biostatistics, University of Pittsburgh Graduate School of Public Health.
"However, we were surprised to learn that the time when the first rejection occurs is crucial for determining the rate of chronic rejection and graft survival. Acute rejections that occurred within the first 30 days were characterized by greater severity and higher odds of graft loss within the first year,” he reported.
Twenty-seven percent of these patients lost their grafts within the first year compared to 12 percent of patients who had a severe, acute rejection after 30 days. However, the later post-transplant course for these patients became much more favorable than for their counterparts for all major transplant outcome measures, including graft survival and incidence of acute and chronic rejection episodes.
While having a match put patients with hepatitis C or primary biliary cirrhosis (PBC) at greater risk for disease recurrence, a mismatch significantly decreased the risk of recurrence of these diseases.
For patients with hepatitis C, 50 percent who had at least one match with their donor of the HLA-B molecule had recurrence of their disease within two years. But only 25 percent of those patients with mismatches had recurrence of disease within the same time period. For primary biliary cirrhosis (PBC), which tends to recur later, 35 percent of PBC patients with two HLA-DR matches had disease recurrence at five years, compared to 10 percent of PBC patients with no matches or just one match.
Matching had little impact on recurrence of hepatitis B or other types of liver diseases.
"This is valuable information for surgeons to consider in deciding the appropriateness of using donor organs in some of our patients. But whether HLA testing will become routine for liver transplantation remains to be seen," said Dr. Fung.
While the preservation time of a liver of just 12 to 18 hours may not allow sufficient time to perform the test and obtain results before the organ must be used, there may be reason to consider routine histocompatibility testing for living donor liver transplants when the recipient has hepatitis C or PBC, say the researchers. Under these circumstances, surgeons have several days or weeks to perform the overall evaluation of a potential donor and can weigh histocompatibility outcomes along with other measures.
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