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Most people don’t like to be placed on a waiting list. However, for patients with hemophilia and chronic hepatitis C, the timing of placement on the liver transplant list can be a matter of life or death. This article discusses liver transplant from a deceased donor. For information on living donors, see the sidebar “Living Donor Decision” in the article “In for the Long Haul,” HemAware May/June 2009.
“My dad really felt that it took so long to get the transplant, that his body was done,” says Dawn Rotellini. Her father, Bob Seifert, received a new liver on Thanksgiving Day 2006. The retired phone company manager from Valrico, Florida, was 65 years old at the time. “Before the transplant, he looked older than my 90-year-old grandfather. I wondered how he was going to survive surgery,” says Rotellini, regional director of chapter services at the National Hemophilia Foundation (NHF). Rotellini is based in Pittsburgh.
Seifert survived the transplant, but five days later he had a severe reaction to the immunosuppressant drugs. “Seizure-like symptoms,” his daughter recalls, led to a stroke and a month-long coma. By March 2007, Seifert was on a respirator; his kidneys and other organs were shutting down. A month later, he died. “With earlier evaluation, he would have been in the system earlier when he was healthier,” Rotellini says.
Liver transplants can have good outcomes if patients know what to ask their hematologist, when to confer with a hepatologist (liver specialist) and when to be listed in a national liver transplant database.
Hepatitis C Virus
Before the development of improved methods for blood safety in the mid-1980s, NHF estimates that approximately 6,200 people with bleeding disorders contracted hepatitis C virus (HCV) from their factor products. Because HCV can take decades to destroy the liver and initial symptoms are typically mild, patients often disregard it.
Seifert, who had mild hemophilia B, was infected with HCV in the mid-1970s. After sustaining a thigh bleed from a water-skiing accident while vacationing in a remote area of North Carolina, Seifert was driven six hours to the nearest hospital, Emory University Hospital in Atlanta. “As ice didn’t work and cryoprecipitate was not an option for hemophilia B, he was given a whole-blood transfusion,” Rotellini recalls. Symptoms of HCV surfaced two weeks later. “He developed flulike symptoms and fatigue,” she says. The lethargy that set in seemed too prolonged for the flu. “But he blew it off, and eventually it went away.”
Seifert’s HCV diagnosis was confirmed in the mid-1980s. His general practitioner told him to return annually for an exam to see how he was doing. “At that point he did not know what the long-term effects of hepatitis C were,” Rotellini says.
Now there is much knowledge on how HCV damages the liver and other organs. As the virus penetrates the liver’s cells, called hepatocytes, it causes fibrosis, the accumulation of scar tissue. If untreated, severe scarring, or cirrhosis, can then lead to end-stage liver disease (ESLD)—liver failure. To prevent destruction of the liver, a combination of two drugs—ribavirin and interferon—is typically recommended. However, they can cause severe side effects, and fewer than 50% of patients clear the virus.
Symptoms of End-Stage Liver Disease
Symptoms of end-stage liver disease can be absent or subtle. “They can be so nonspecific that you don’t pay any attention to them—you’re a little fatigued or you have a change in your sleep/wake cycle,” says Margaret Ragni, MD, MPH, director of the Hemophilia Center of Western Pennsylvania and professor of medicine at the University of Pittsburgh. “You can also develop ascites, fluid buildup in the abdomen.” It’s easy to attribute feeling tired or gaining weight to a sedentary lifestyle or getting older, she says.
Liver disease can alter bleeding symptoms. “Your platelet count can fall just a bit,” Ragni says. This can cause more frequent nosebleeds or gum bleeds after brushing your teeth. Another sign is that you need more clotting factor to treat joint bleeds, she says. “You may not put any of these things together until you develop more severe symptoms—vomiting blood or having a gastrointestinal bleed, a common problem,” says Ragni.
Seeing a Hepatologist
While a hematologist can order standard liver function tests, a specialist is needed for more in-depth studies. “When the liver disease becomes more invasive, you need a hepatologist who knows which scans and tests should be done,” Ragni says. Hepatologists can gauge if your liver disease is progressing quickly, which treatments might help and how often you should be monitored. “They are the experts at managing long-standing hepatitis C.”
Ideally, the hepatologist should be associated with a major transplant center and work with the hematologist at your hemophilia treatment center (HTC). “In the mid-1990s, as part of my care at the University of California, San Diego Hemophilia Treatment Center, patients who were hepatitis C positive were told they should be followed by a hepatologist,” says Glenn Pierce, MD, PhD, vice president and chief medical officer of Biogen Idec’s hemophilia therapeutic area in Waltham, Massachusetts. Pierce, 55, contracted HCV from a blood transfusion to treat his severe hemophilia A in the mid-1970s.
The hepatologist can address your questions or concerns about liver transplantation. In 2003, Pierce began that dialogue after moving his care to the HTC at the University of California, San Francisco. “As a pre-emptive measure, they asked me to begin to get a workup for a liver transplant,” Pierce says. He was reluctant, but they were persistent. “It was really UCSF that took this very, very seriously. They told me, ‘You’ve got to deal with this now.’”
[Steps for Living: Talking to Health Care Providers]
Importance of the MELD Score
The national database for liver transplants is coordinated by the United Network for Organ Sharing (UNOS), which holds the federal contract to operate the Organ Procurement and Transplantation Network (OPTN). To be listed, you must have a Model for End-Stage Liver Disease (MELD) score. The score uses a mathematical formula to calculate a patient’s risk of dying from liver disease within the next three months. The MELD score has three components, derived from blood tests:
- Bilirubin: a waste product of red blood cells. When the liver is damaged, it builds up in the body.
- Creatinine: a waste product produced in the muscles and excreted by the kidneys. High levels indicate liver disease.
- INR (international normalized ratio, also called prothrombin time): a measure of how long it takes for blood to clot.
These values are plugged into a formula, which produces a score indicating liver disease severity. The MELD score ranges from 6, least severe, to 40, most severe. Online calculators make it handy for patients or HTC staff to figure out the MELD score in the office. (See article "Patient Checklist for Hepatitis C Evaluation.") “It works as well in HIV patients as it does in non-HIV patients,” says Ragni. “It’s a very good predictor.
“This set of criteria for the MELD score can clearly tell you when you’ve progressed to the point where your liver is functioning so little that your quality of life is poor and your risk of dying is high.” That’s the time that the transplant option is proposed. “It’s not something that is used indiscriminately,” Ragni adds.
There are more than 200 transplant hospitals in the US; approximately 20 are HIV+ transplant centers. The transplant team determines if you are a good candidate, based on such factors as:
- Your physical and mental status
- Commitment to avoid drugs and alcohol that could damage the new liver
- Financial situation
- Level of support at home
If you make the grade, your name is added to the national list.
Pierce was placed on the national transplant list in the spring of 2008, when his MELD score was 15–16. “That’s when my hepatologist strongly advised it was time to get the full workup for a liver transplant.” That workup involved a summer of testing on major organ systems of the body, from the cardiovascular system to the pulmonary system and gastrointestinal tract, to ensure they could support such a major operation.
Seifert’s scenario was different. “He was on a transplant list, but it was affiliated with a local hospital, not a major transplant center,” says Rotellini. Although Seifert’s MELD score values were normal, Seifert was suffering. He had profound fatigue and ascites, which was periodically drained. He was told, “You’re not bad enough to be put on an active list.”
“The hurdle for my dad was not knowing what to ask. When was the right time to aggressively get on a transplant list?” Rotellini says. She persuaded her father to transfer to a major transplant center in Gainesville, Florida, two hours away. The transplant team there did the full physical workup and more. “They evaluated his mental status and support system, too,” Rotellini says. “You really have to have a great support system after the transplant.”
There is no standard MELD score that automatically places you on the liver transplant list. “Each institution establishes the range at which it transplants; very often it’s in the high teens,” Ragni says. Some regions with high demand for liver transplant, such as the Northeast and California, require a MELD score in the upper 20s or low 30s.
“If I had waited for my MELD score to reach 25–30, there was a high risk of not coming out of the transplant,” says Pierce. Data support Pierce’s argument. According to the 2009 Annual Report of the OPTN/Scientific Registry of Recipients, patients whose MELD score was 11–20 at the time of transplant survived longer than those with scores above 30.
Some conditions can automatically move you up on the list. “If you develop hepatocellular carcinoma (liver cancer), that puts you much higher on the list. You can get the transplant before the cancer spreads outside the liver,” Ragni says.
But the MELD score and liver transplant ranking are imperfect. They don’t take into account the unique health conditions of people with hemophilia, HCV and HIV. “The results of an unpublished study I’ve conducted show that once people with hemophilia get on the waiting list, they do not do so well,” Ragni says. “I believe it’s because they progress faster because they’ve had hepatitis C longer.”
“I don’t think the MELD score accurately reflected my diagnosis,” Pierce says. His platelet count was below 40,000. The normal range is 150,000–400,000 platelets per microliter. Further, several other clotting factors made by the liver were less than 20% of normal. In addition, his albumin count was so low he had edema, or swelling. “None of these factors are taken into account by the MELD score,” says Pierce. They add significant risk to the survival rate of patients with hemophilia who are also lacking either factor VIII or IX, he says.
The story of Pierce and Seifert is the tale of two men with liver disease who underwent liver transplantation. One made it; the other did not. Knowing what to look for and when, who to consult and how far to push might make the difference in the end. “The ultimate goal is to get a transplant before your body shuts down—to do it while your body is still healthy enough to survive the surgery and the immunosuppressant drugs, because they do take their toll,” Rotellini says.