Mismatched Livers Could Be Match From Heaven

Study finds less disease recurrence after donation

TUESDAY, April 30, 2002 (HealthDayNews) -- It might seem to offend common sense, but some liver transplant recipients might be better off with an organ deliberately chosen to be an immunological mismatch.

A mismatched liver does invite rejection by the body's immune system, but it also reduces the chance that some conditions causing liver failure will recur, concludes a new study of more than 3,000 transplant recipients at the University of Pittsburgh.

Additionally, rejection is much less of a problem for livers than for other transplanted organs -- so much so that doctors do not usually test to see whether the donor liver matches the recipient's human leukocyte antigens (HLAs), which signal whether the immune system is attacking or tolerating the transplant. Instead, they pay closer attention to blood type compatibility and the size of the liver, to make sure it will fit the recipient.

"For a long time, we thought that with liver transplants we didn't have to do typing, because there is no impact of typing on rejection," says Dr. John J. Fung, professor of transplantation at the university's Thomas E. Starzl Transplantation Institute. "This is an immunological privilege we don't really understand."

Nevertheless, the institute has been checking on the donor-recipient match and following the results of the operations. Jung is scheduled to present the results today at the American Transplant Congress meeting in Washington, D.C.

The impetus for the study came from a paper the Pittsburgh doctors published a decade ago, showing that patients receiving immunologically matched livers had a lower survival rate than those getting mismatched organs. The new study shows reduced survival occurs because "better matching does lead to less rejection, but more diseases come back," Fung says.

That is not true of all liver-destroying diseases, but it is true for hepatitis C infection, the leading cause of liver failure, the study finds. A quarter of all liver transplants are needed because of hepatitis C.

For patients with hepatitis C, 50 percent had recurrence of the disease within two years after transplant if there was at least one HLA match; the recurrence rate for mismatched organs was 25 percent. And for another major cause of liver failure, primary biliary cirrhosis, there was a 35 percent recurrence rate within five years for two HLA matches, compared to 10 percent for no matches or just one match.

"This opens the possibility that a deliberate mismatch should be attempted in some cases," Fung says.

Not all cases, he emphasizes. For childhood diseases that cause liver failure and for cases of autoimmune disease, among others, a good match should be sought, he says.

The study does show that when recurrence of disease is not a problem, a good immunological match improves the chance of a good outcome because it reduces the incidence of rejection, short-term and long-term, says Ivor Dvorchik, another study participant. Another finding is that the timing of rejection by the immune system is extremely important, he says.

"Rejections that occurred in the first 30 days were characterized by greater severity and higher odds of graft loss in the first year," Dvorchik says.

The suggestion of seeking a mismatch for specific patients is bound to be controversial, Fung says.

"That is our hypothesis," he says. "But we have to prove it, and then the transplant community has to approve it."

What To Do

Since there never are enough donor livers to meet the need, you might consider signing a donor card.

You can learn more about liver disease from the American Liver Foundation. Interested in becoming a donor? Try the United Network for Organ Sharing.

SOURCES: John J. Fung, M.D., Ph.D, professor, transplantation, University of Pittsburgh Thomas E. Starzel Transplantation Institute, Pittsburgh; Ivor Dvorchik, Ph.D., director, section of biostatistics, University of Pittsburgh Thomas A. Starzel Transplantation Institute, Pittsburgh; April 30, 2002, presentation, American Transplant Congress meeting, Washington, D.C.
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