The 42-year-old nurse practitioner hadn't felt well for nearly three months, taking extra vitamins to boost her immune system. By early November, jaundiced, tired, and struggling to do simple tasks such as getting dressed, Ms. Clark went to her primary care physician, who ordered blood work and an ultrasound. The blood tests came back negative for Hepatitis A, B, and C, but her liver enzymes were 60 to 70 times the normal level. The doctor concluded that she had some type of hepatitis and recommended rest and plenty of fluids.

On November 22, the day before Thanksgiving, the New Jersey woman was acting confused and was barely able to walk. "I'm told I yelled at my daughter, which is totally out of character for me," she says. "I was very tired and was taken upstairs to sleep." When Ms. Clark's husband came to check on his wife, he couldn't wake her and called 911. She lapsed into a coma and was placed on life support at a local hospital. The gastroenterologist on call took one look at her and said, "She needs a new liver." His first impression was found to be correct, and Ms. Clark was taken to University Hospital, site of the nation's 13th most active liver transplant center.

Dr. Baburao Koneru, chief of the liver transplant program and associate professor of surgery at New Jersey Medical School, gave Ms. Clark's family grim news. She had acute fulminant viral hepatitis, a quickly progressing attack on the liver that proves fatal about 80 percent of the time. Unless a suitable donor liver became available within 72 hours, said Dr. Koneru, Ms. Clark would die. On the United Network for Organs Sharing (UNOS) system, she was at the highest priority level to receive a donor liver.

Next comes the part of Ms. Clark's story that she finds especially difficult to tell. "That Sunday, while I was still in a coma, a match donor liver became available. With no living cells left in my liver, I received a transplant," she says. "It's frightening for me to say that because many people wait for a new liver for months and even years. Receiving a donor liver that quickly is a very rare and miraculous occurence."

Today, Ms. Clark is back at work, sending a child off to college in the fall, and renewing her wedding vows, with friends and family from around the country as witnesses. And while her life will never be what exactly what it was before Thanksgiving Eve 2000, she's grateful for it and the person who made it possible. "I know that my liver came from an Alabama woman who was my age," she says. "Her liver was a perfect fit, and she's been wonderful to me. I say 'thank you' to her every day."

The Causes of Liver Failure

Very few people develop fulminant hepatitis, believed to result from another strain of hepatitis; a severe reaction to medication, such as halothane, an anesthetic gas; or a toxic liver injury, such as can occur with an overdose of acetaminophen. But there are many other reasons why more than 17,500 people (about 7 percent of them under age 18) are waiting for a liver.

The liver is not only the body's largest internal organ; it's extremely versatile. Among the liver's 500 jobs, it produces bile, a secretion that prepares fats for further digestion. Remarkably, in most cases, a healthy liver can also repair itself.

Not all livers are in prime condition, however. Certain rare disorders can affect adults and children. For example, biliary atresia -- the blockage or absence of the small tubes or ducts that carry bile from the liver to the small intestine -- is the leading reason for liver transplant in children. When other treatments for liver tumors have been exhausted, a transplant can be the last option. Eating wild mushrooms or taking excessive amounts of acetaminophen can also cause acute liver failure. Cirrhosis, in which a build-up of scar tissue hampers blood flow through the liver, can be caused by long-term alcohol use or as a manifestation of other conditions, such as hepatitis. Symptoms of liver disease include a yellowing of the skin or eyes (jaundice), fatigue, weight loss, and itching all over the body.

Hepatitis, literally, inflammation of the liver, can be caused by one of several, distinct viruses. Hepatitis A is contracted via contaminated food or water, and Hepatitis B is transmitted primarily through sexual contact; there are vaccines for both of these viruses. Years ago, other types of hepatitis was referred to as non-A, non-B Hepatitis, but researchers further identified these strains, which are now known as Hepatitis C, Hepatitis D, and Hepatitis E.

The most common reason for liver transplantation, and one that will escalate over the next several years, is Hepatitis C (HCV). Cirrhosis from Hepatitis C is the primary reason for half of the liver transplant cases at University Hospital -- more than all the remainder of the cases combined. According to Centers for Disease Control (CDC) estimates, 3.9 million Americans are infected with HCV, 2.7 million of them chronically. Chronic HCV, for which there is no known cure, can lead to cirrhosis or hepatocellular carcinoma, a malignant liver tumor. Not all cases of HCV progress with the same degree of severity, and some patients respond better to treatment than others.

HCV is transmitted when blood passes from an infected person to an uninfected person. Dirty needles and infected blood are the most common modes: IV drug users (even those who experimented once), people who received blood clotting factors made before 1987, and those who had blood transfusions before 1992 are at the highest risk. Earlier this year, actress Pamela Anderson revealed she contracted HCV from tattoo needles. Babies born to HCV-infected mothers, or healthcare workers who sustain an accidental needle stick, have a much lower, but still feasible, risk of getting HCV.

"We're at the stage with the Hepatitis C virus today that we were with the human immunodeficiency virus (HIV) about 15 years ago. A person with HIV was given little hope. But over time, with the development of more effective treatment, HIV is not as problematic in the United States as it once was," says Dr. Koneru. "Great progress has also been made with the Hepatitis B virus, which used to be the primary reason for many liver transplants. With the availability of a vaccine and several drugs for treatment, Hepatitis B has become a much more manageable condition. The difference between 10 years ago and today is dramatic."

The drug therapy for HCV is a combination of alpha interferon and ribavirin, two anti-viral agents. This treatment, which lasts between 24- 48 weeks, is not always an easy road--interferon is delivered by injection three times a week, and side effects include flu-like symptoms and, in some cases, irritability and depression. It is hoped that with treatment, patients will be able to achieve a sustained viral response, meaning that tests show no signs of HCV for at least six months after treatment. One study showed sustained viral response rates following alpha inteferon/ribavirin therapy ranging from 33% to 41% for the 24- and 48-week treatments, respectively.

A newer regimen of pegylated interferon, a modified version of interferon, and ribavirin has been shown to be more effective in producing a sustained viral response, even in the more resistant genotype 1 form of HCV. Overall, the therapy has a sustained response rate of about 55%(ranging from 42% with genotype 1 to 82% with genotypes 2 and 3, according to the American Liver Foundation. Says Dr. Koneru, "The new drug therapies for Hepatitis C show cause for optimism and hopefully, some day there will be a vaccine."

Still, HCV is a major public health concern that will confront liver specialists and transplant teams for years. That's because the virus progresses slowly, and an infected person might not have symptoms such as jaundice, dark-colored urine, and fatigue until 10 to 20 years after contracting the virus--if the person feels sick at all. According to the CDC, 80 percent of infected people have no signs or symptoms of the virus. Many find out they have the virus when they go to donate blood or have pre-surgical blood tests.

"The full effect of HCV hasn't been felt yet, but it's coming," says Dr. Koneru. "The anticipated need for liver transplants is tremendous. The dilemma is how to provide livers for people who need them." (Read about liver donation in the sidebar, "The Gift of Life.")

An Experienced Team

Although Dr. Koneru's team has an eye for this future need, the focus is on treating patients today. "We want to provide livers to as many recipients as possible with excellent, comprehensive care before, during, and after the transplant," he says. The team is a designated group that includes surgeons, liver specialists, physician assistants, a psychiatrist, nurse coordinators, social workers, financial aid staff, and nutritionists.

More than 500 liver transplants have been performed at University Hospital since the program's inception in 1989, and Dr. Koneru has done more than 300 of the complicated procedures. University Hospital survival rates are 93.84% at one year post-transplant and 89.95% at three years. The national average rates are 87.0% at one year and 80.9% at three years.

"Survival rates are rising worldwide, but they also tend to improve as the liver transplant team becomes more experienced," says Dr. Koneru. "We have better anti-rejection medications available today and are encountering fewer post-transplant complications."

A patient's acceptance into the Liver Transplant Program is based on several factors, primarily the results of a thorough medical evaluation, including testing, and psychosocial and nutritional assessments. A hospital-based, multidisciplinary selection committee makes the final decision, and patients accepted into the program are placed on the national UNOS waiting list.

Learn more about organ donation and how you can help. Click Here.

This year, UNOS implemented a new system for prioritizing patients waiting for a liver transplant. The Model for End-Stage Liver Disease (MELD) and the system for pediatric patients, the Pediatric End-Stage Liver Disease (PELD), use statistical formulas to predict which patients are in the greatest need of a new liver. With the new system, which became effective in February, patients are assessed on a scale from 6 (less ill) to 40 (gravely ill). MELD uses a more objective method of categorizing patients than the old system, which relied in part on physicians' interpretation of symptoms.

Patients' placement on the UNOS list changes as their health status changes, and the wait for a liver can be days, weeks, or months. The new liver usually comes from a deceased organ donor with the same or compatible blood type as the receipient and about the same body size. "Living donor" procedures can be performed in certain cases--typically from an adult to a child.

Once a new liver is available, it is delivered to the hospital, where it is inspected by the transplant team. The complex operation takes between 6 and 12 hours. In very simple terms, the diseased liver is removed and the healthy liver is attached to the blood vessels that feed and drain the organ and to the bile ducts.

After three to four days in a surgical intensive care unit and another four to five days on a nursing floor at University Hospital, the transplant patient goes home to begin a new, lifelong regimen that includes anti-rejection medications, regular liver function tests, and daily living changes, from scrupulously avoiding infection to dietary recommendations. It's estimated that between 60 percent and 70 percent of liver transplant recipients will experience signs of rejection at some point, but very few will need another new liver.

Bill Thomas* knows all about new beginnings. Three years ago, when he was scheduled for vascular surgery on his legs, his platelet count was low. Further tests showed that he had cirrhosis of the liver, the result of too much drinking in the past. "It took me by surprise, because I felt like nothing was wrong with me," recalls Mr. Thomas. "I'd been clean for several years, but the damage to my liver was already done."

The 57-year-old received his transplant at University Hospital in January, when he had only 25 percent function in his liver. Mr. Thomas knew he was living on borrowed time, but "I put it in God's hands." When a liver became available, reality didn't sink in until he reached the operating room. Like Ms. Clark, he is deeply grateful to his donor and wrote a "long letter" to the donor's family.

Mr. Thomas says that although the surgery went well and he had very few complications, he's still in the healing process. He walks a couple of blocks sometimes, savoring the day and looking ahead to tomorrow. "My wife and I have a daughter," he says. "I hope some day to walk her down the aisle."

*Names have been changed

For more information about the Liver Transplant Program at University Hospital, visit our web site at:

www.TheUniversityHospital.com/livertransplant

or call (973) 972-7218.