Bloom when you are transplanted

The promise of living a normal life with a total reversal of symptoms is the motivation for people with compromised liver function to get a transplant.

by Jon Nalick

In 1994, Mel Creighton, an energetic 48-year-old businessman and avid surfer, puzzled over the news that his life insurance policy application had been denied based on a 10-minute medical exam and blood test.

Declining to state the reason, the insurer suggested he review his test results with his physician, who ran more tests and suggested he see a specialist.

Creighton, who felt fine and was growing exasperated by the lack of a straight answer, was floored when he finally got one.

Without prelude, the specialist bluntly pronounced: “You’ve got terminal liver disease and maybe a 25 percent chance of survival.”

A few months later, the first symptoms of primary sclerosing cholangitis—a disease of unknown cause that attacks the liver bile ducts and leads to cirrhosis—appeared. Over the next few years, the symptoms worsened considerably, and by 2002, Creighton itched so severely that he scratched himself bloody in his sleep. He suffered persistent nausea, stomach upset, insomnia and fatigue. His skin and the whites of his eyes turned rusty yellow.

Creighton, now 58, says, “at that point, a liver researcher at UC Irvine told me that there are five stages of my disease. He told me the fifth stage is death and I was well into stage four. He said it was time to start thinking about a liver transplant.”

After researching his options online and talking to medical experts, Creighton chose to go to the Liver Transplant Program at USC University Hospital. Directed by Rick Selby, M.D., Keck School of Medicine professor of surgery, the transplant team includes Nicolas Jabbour, M.D., associate professor of surgery, and Yuri Genyk, M.D., assistant professor of surgery, both also at the Keck School.

“The more I investigated, the more I felt that Selby, Genyk and Jabbour were the best in the world,” Creighton says.

But as his illness suddenly worsened to the point that he might not survive the three-to-five-year wait for a donor liver, the only question was whether he had found them in time.

The first human liver transplant was performed in 1963, but it was not until 1996 that the Keck School of Medicine recruited a liver transplant team.

Even so, within just a few years, the team began performing more surgeries than most established liver transplant programs. Today, the group performs about 90 transplants each year, and is the nation’s fourth largest program for adult live-donor liver transplants. At the same time, it acquired a reputation for its expertise and innovation—especially in performing “bloodless” transplants that eliminated the need for donated blood.

“We were actually the last team to form in the Los Angeles area,” Selby says. “But we’re the first program on the West Coast to do adult living-donor transplants and are still the only one that does bloodless adult living-donor transplant surgeries. We get referrals from other centers because no one else wants to do those operations because they’re so technically difficult and there’s no margin for error.”

The liver transplant team is composed of about 50 members, including surgeons, hepatologists, transplant coordinators and a transplant administrator. The surgeries are long and complex, requiring two teams working simultaneously in cases with a living donor. They also are expensive.

But Selby says they also are extraordinarily effective: The program’s one-year survival rate is over 90 percent for adults. Further, the unit’s pediatric liver transplant program at Childrens Hospital Los Angeles has the highest success rate—95 percent—of any in the country.

Selby says that the best part of his job is seeing how success in the operating room translates into a new lease on life for a patient.

“The nice thing about a liver transplant is that you generally see a total reversal of symptoms afterward,” Selby says. “In medicine, it’s a rare event that a physician can bring about a true reversal of a serious chronic illness. The best you can usually do is hold the line and prevent further loss of function.

“With a liver transplant, you can sometimes return a person to a level of function they have not experienced in 20 or 30 years: The loss of muscle mass reverses, as does the loss of reproductive and sexual function. People who have been sick or bedridden for months or years regain their health so completely that they can return to work.”

The liver’s chief function is to help the body store starches and fats, produce proteins and clear poisons from the blood. It also plays a role in supporting the body’s immune system.

The need for liver transplants most typically arises from chronic conditions such as viral hepatitis, liver cancers or cirrhosis that attack the liver over the course of many years. The deterioration of the liver results in increased retention of abdominal fluid, loss of muscle mass, loss of sexual and reproductive function, and blood clotting disorders. Because the liver detoxifies the blood, liver failure typically results in a slow poisoning of the body and death within 48 hours if untreated, Selby says.

Although tissue matching for other types of transplants must be exceedingly precise, the body is relatively forgiving about accepting a new liver: Only a simple blood-type match and size match are required. Even so, donated livers remain in short supply. As many as 20 percent of those who need a new liver will die waiting for one to become available, so the operation is generally one of last resort, Selby notes. For those who do receive a new liver, however, fully 90 percent will survive one year and continue living a relatively normal lifespan.

Most livers come from cadavers, and the organ can remain viable for as long as 15 hours following recovery. Useable organs also may come from living donors who supply just a portion of their own liver. Because of the liver’s regenerative abilities, both the donor’s liver and the donated section of liver will grow back to the size of a healthy organ within several weeks.

Still, live-donor operations are more complex; they require the utmost care to ensure that, in making a sick patient well, the physicians do not harm a healthy person.

Creighton’s case is typical of those the program deals with, Selby says.

“The average patient we treat is a 55-year-old with chronic hepatitis, frequently contracted through a blood transfusion, and they’ve suffered from it for years. They haven’t been able to work and most are in intensive care by the time of the transplant. It’s a miserable existence,” he says.

To be eligible for a transplant, a patient must have sufficient blood flow to the liver and be free of significant heart and lung disease. Available cadaveric organs are apportioned through a regional matching system, with the sickest individuals moved to the front of the line.

For Creighton, whose health in spring of 2003 had taken a dramatic turn for the worse, any wait was tantamount to a death sentence.

“My doctor said that not only might I not survive the waiting list, but that I might not survive the summer. Even if I did, my other organs would become so damaged that it would make a transplant useless—so that news to me was just thermonuclear,” he says.

Creighton sought out friends and family as potential donors, but no viable matches resulted. Out of frustration, Creighton’s wife Carol asked to be tested over the transplant team members’ objections that her age—she was then 57 and above the 55-year cut-off point—made her ineligible no matter what the results. But she matched and ultimately persuaded the team to accept her as her husband’s donor.

On June 3, 2003, the transplant team performed a rare wife-to-husband liver transplant.

Over the next month, Carol Creighton recuperated quickly, while Mel Creighton endured a rocky recovery, marked by extreme fatigue, hallucinations and a liver-rejection scare.

“All the while, Drs. Selby, Jabbour and Genyk were just great. And the nurses would come in after their shift was over—it was obvious how tired they were, but they came in to talk and encourage me. It was just wonderful. The care I got was far beyond anything I could have expected. It was beyond exemplary,” he says.

“They’re a great team,” Carol Creighton agrees. “A great team.”

As many as 8,000 Americans receive liver transplants each year, and the average person will spend two to three weeks in the hospital afterward and then several months recovering while the liver attains full function. The biggest challenge is the post-operative recovery period, during which patients must remain on powerful immunosuppressive drugs. The drugs are potentially toxic to the nervous system and the kidneys, so dosages must be monitored closely since patients will remain on these drugs for life.

“There is a broad array of drugs to choose from, so the strategy is to figure out which combinations at which dosage will minimize the side effects,” Selby says.

A significant portion of the liver transplants the team performs are on children who most frequently require the transplants for illnesses such as biliary atresia or acute liver failure, liver tumors or metabolic disorders.

Dealing with these patients—some as young as one month old—presents challenges over and above what can be expected for adults, Genyk says.

Pediatric transplantations “add a layer of complexity that reduces the margin for error to nearly none. You have to be very precise with all the medications and immunosuppression, and it’s a more delicate operation” partly because the blood vessels and bile ducts are so small in children, he says.

Additionally, children do not receive a whole organ, but rather a small segment of an adult liver, so the sudden physiological demand placed on it accounts for some of the higher complication rate children have from the surgery.

“The good news is that we manage to keep our complication rate to a minimum and the kids can usually expect a healthy life after transplant—basically the same as if they had never been sick,” he says.

And that, he adds, “is extremely emotionally satisfying.”

In a tradition that underscores that feeling for the entire transplant team, patients and their families are invited back to Childrens Hospital Los Angeles for an annual party with the physicians and staff.
“It’s very gratifying to see these kids every year and see how fast they grow up—sometimes you almost don’t even recognize them,” Genyk says.

In addition to pediatric transplantation, the USC team has developed an unusual niche in performing “bloodless surgery,” which was originally designed to serve patients who refused blood transfusions for religious reasons, but now is used with scores of patients.

A simplified description of how transfusion-free surgery works is that the physicians transfer one to four units of blood from the patient into a special bag, but leave it connected to the patient through a tube. At the same time an intravenous fluid is infused into the patient, keeping the volume of liquid in the arteries, veins and the rest of the vascular system steady while diluting the remaining mass of blood cells. Any blood lost during the surgery is salvaged and re-infused into the patient.

Jabbour says that because the blood is always connected to the patient, there is no risk of mismatched blood due to clerical error—a small but acknowledged risk in other transfusions.

He advocates the technique because repeated transfusions may increase the risk of infection and potentially suppress the immune system of the patient. Many patients who require liver transplants have hepatitis C, which they contracted from long-ago blood transfusions, he says.

USC surgeons and physicians are known pioneers in transfusion-free techniques, which are now used not only for surgeries of the liver, pancreas and the biliary tree, but in cardiac, orthopaedic, vascular, thoracic and plastic surgery and neurosurgery.

“In the future, we see bloodless surgery as the standard of care for any patient,” Jabbour says. “Avoiding blood loss and using blood products judiciously just make for a better surgery.”

In December 2004, after nine months of comparative good health, Creighton suffered a blockage in his liver that required emergency surgery. He is scheduled for another doctor visit and will soon start a new drug regimen to treat the complication.

Still, he says he has no regrets about the transplant: “Without it, I wouldn’t be looking at the grass from the green side now. The surgery was the best thing that ever happened to me. So far, it’s given me 18 months more of life.”

He adds: “The other day, Dr. Selby told me, ‘I’m expecting another 20 years out of you.’ I laughed and told him, ‘I’m expecting another 40.’”

For more information about the liver transplant program, call 1-800-USC-CARE (1-800-872-2273). More information about transfusion-free surgery can be obtained by accessing the USC Health, Fall 2004, “All You Need is Blood” story at www.usc.edu/hsc/info/pr/hmm/04fall/blood.html or by contacting Randy Henderson, director of transfusion-free medicine at USC University Hospital, at 1-800-USC-CARE.