Liver transplants from living donors had already been losing momentum around the nation by the time UPMC transplant pioneer Thomas Starzl weighed in on the topic recently.
But as the first doctor in the world to perform a liver transplant, his critical perspective on 121 of those transplants at UPMC between 2003 and 2006, which revealed a high complication rate, is certain to ramp up the debate among transplant physicians and ethicists on this controversial procedure.
The recent study looked at the period when living donor operations surged at UPMC under the leadership of Dr. Amadeo Marcos, who was forced to resign last year amid sexual misconduct allegations.
That rapid increase was an anomaly in the United States, where the operation has been declining since 2001.
Living donor liver transplants peaked nationally at 524 in 2001, when they comprised 10 percent of all liver transplants. By last year, they had dropped to 249, and accounted for just 4 percent of liver transplants.
That's a marked contrast to living donor kidney transplants, which now make up nearly a third of all kidney transplants in America. Living kidney operations not only are safer to perform than living liver transplants, but live-donor kidneys function significantly better than deceased donor kidneys do.
At UPMC, the number of living donor liver transplants has plummeted since Dr. Marcos left, from more than 30 a year at his peak to just four last year.
UPMC spokesman Paul Wood said last week that the dwindling number of living donor transplants does not reflect any change in policy, but simply the fact that "when you have a world-famous surgeon like Dr. Marcos who was a pioneer in living donor liver transplants, and he leaves, a decrease in numbers is a natural consequence of that."
He said neither Dr. J. Wallis Marsh, lead author of the Journal of Hepatology study that also included Dr. Starzl and two others, nor Dr. Abhinav Humar, new chief of transplantation, wished to comment for this article. Dr. Starzl also declined comment.
At the national level, there are at least three reasons living donor surgeries have declined, according to a report last year by Dr. James Trotter, medical director of liver transplantation at Baylor University Medical Center in Dallas.
The first is what he called the "front-loading" effect, meaning that the best matches between donors and recipients were done early in the process, after adult-to-adult liver transplants began 10 years ago.
The second is that thanks to a concerted national effort to increase organ donations, the number of deceased donor transplants increased by nearly 30 percent between 2001 and last year, to 6,070 transplants.
Finally, he wrote, doctors began to realize that the results of living donor transplants were not quite as good as they had originally thought.
Initially, they touted the fact that the survival of living donor patients was better than those who got cadaver organs. But that was influenced by the fact that most people getting living donor transplants were much healthier than those getting cadaver organs, largely because national policies dictate that deceased donor organs go to the sickest patients on the waiting list.
Still, some experts feel that correlating the survival of those who get live organs with those who get cadaver organs is the wrong comparison to make.
"The fundamental choice patients are making is not a living donor organ vs. a deceased donor organ; they're deciding between a living donor transplant today vs. staying on the waiting list with the potential for getting an organ in the future," said Dr. Robert Brown, medical director of the Center for Liver Disease and Transplantation at New York Presbyterian/Columbia.
And for now, Dr. Brown said, the chance of people dying while on the liver transplant waiting list is greater than 20 percent, while the chance of dying after a transplant is less than 10 percent after one year. "So the real question is, 'What risk should a donor take in order to get the recipient off the waiting list sooner?' "
While the Starzl and Marsh study criticized several aspects of living donor transplants, including the fact that they subject healthy donors to a risky surgery, it didn't call for abandoning the operation altogether.
That's also the position of Dr. Goran Klintmalm, a longtime liver transplant surgeon at the Baylor Regional Transplant Institute and past president of the American Society of Transplant Surgeons.
"I have been quite public in saying that, to me, you have to have a really good reason before you expose a healthy human being to the risks that are entailed in living donation," Dr. Klintmalm said. "In kidney transplantation, the risks are very small if done correctly. In liver transplantation, just as Tom [Starzl] brings up, the question is, when is the risk to the donor so high that you have a hard time justifying it?
"I don't think there is an easy straightforward answer to that because I don't think we as a society have really figured out what the risk and benefit balance is."
One key, he said, is to find potential recipients who are neither too sick nor too healthy.
Liver disease patients who are very sick don't do well with any kind of transplant, he said, but have an especially tough time if they get a living donation. Since living donor patients are only getting about 40 percent to 60 percent of the donor's liver, there sometimes isn't enough tissue to overcome the shock of transplant surgery, Dr. Klintmalm said.
On the other end of the scale, studies have shown that for relatively healthy liver patients, the risk of surgery is a greater threat to their lives than waiting until they are sicker.
To determine how sick a patient is, liver specialists use a national rating system called MELD -- Model for End Stage Liver Disease -- which ranges from 6, for very healthy, to 40, for extremely ill.
Most living donor programs have now agreed it is too risky to transplant any patient with a MELD of less than 15, even though at UPMC, 70 percent of the patients transplanted by the Marcos team had MELD scores of 15 or less.
In his view, Dr. Klintmalm said, "somewhere between a MELD of 15 and 28 is the ideal window" for living donor transplants.
Even with healthy recipients, though, there is the issue of complications. The Starzl and Marsh study said that 66 percent of living donor liver recipients at UPMC suffered serious postoperative complications.
That was more than twice the rate cited in a study of nine top living donor programs across the nation, although UPMC's Mr. Wood said that "we believe it is possible the complications at other centers may have been underreported. We believe our researchers used a more rigorous system and more rigorously applied the criteria" to track postoperative problems.
If that is true, though, it would mean that more than half of all living donor recipients in America may suffer potentially life threatening complications.
Dr. Satoru Todo, a liver transplant surgeon at the Hokkaido University Graduate School of Medicine in Japan, said in an e-mail interview that living donor transplants are a challenging type of surgery.
"It is a technically demanding surgery," Dr. Todo said, "and is complicated by such postoperative problems" as clots in the liver's main artery, bleeding, retention of fluid in the abdomen and narrowing or blockage of the bile duct.
Even so, Asian centers have reported much lower complication rates than American hospitals for living donor liver transplants.
Dr. Todo said Asians have a high incidence of liver cancer, so surgeons there are very experienced with liver operations. There is also a cultural prejudice in Asia against donating organs at death, which means that Asian surgeons have few chances to use cadaver organs as a fallback.
Most experts see a future for living donor liver transplants, but it's unclear whether they will regain a bigger share of transplants.
In parts of the United States or the world where there is a good supply of cadaver organs, "the rule should be if we don't absolutely need to do living donor transplants, we should never do them," said Dr. Ronald Busuttil, chief of liver and pancreas transplantation at the David Geffen School of Medicine at the University of California at Los Angeles.
Worldwide, there probably have been more than 30 deaths of donors during this procedure, he estimated, and "that is very much on the minds of most transplant surgeons around the country. We're very reluctant to subject our patients to a living donor transplant."
One important lesson from the Starzl and Marsh study, Baylor's Dr. Klintmalm said, is that it "brings out the whole issue that we need to be careful and not just charge ahead and let cowboys do this [operation]. It has to be done by people with honesty and respect for life and people."
But Columbia's Dr. Brown also pleaded for empathy with donors who want to help people they love. "If you want to respect donor autonomy, you would allow them to take much greater risks than any [liver specialist] would allow them to. I think it's clear donors would take a higher risk for someone they really cared about than medical practitioners are willing to do."