Liver transplant for FAP

Last updated April 4, 2024, by Marisa Wexler, MS
Fact-checked by Marta Figueiredo, PhD

Liver transplant was the first treatment approach to demonstrate an ability to slow disease progression and prolong survival in people with familial amyloid polyneuropathy (FAP), a genetic disorder marked by progressive damage to several nerves, also known as polyneuropathy.

The procedure was first performed in FAP patients in the 1990s. Despite the approval of several treatment options for FAP in the last decade, a liver transplant is still considered for patients who are resistant or intolerant to such medications, or when other therapeutic options are unavailable.

How does liver transplant work in FAP?

FAP is caused by mutations in the gene that provides instructions to make transthyretin, a protein that helps carry certain hormones and vitamins through the bloodstream.

As a result of the mutations, cells produce an abnormal version of transthyretin that’s prone to forming toxic clumps called amyloids. These aggregates accumulate in nerves and, less extensively, in other organs, driving FAP symptoms.

Because most transthyretin is made in the liver, a liver transplant, which involves replacing a patient’s liver with a healthy organ that produces functional transthyretin, has the potential to eliminate the main source of the defective protein.

By lowering the production of the abnormal protein, the procedure serves as an effective amyloid polyneuropathy treatment that can reduce the formation of toxic clumps, which should slow nerve damage and the disease’s progression.

The benefits of a liver transplant in people with FAP

Here we can explain the potential outcomes of the procedure and when it should be performed, or when it’s associated with better outcomes.

The first liver transplant for FAP was performed in 1990, and evidence has shown the approach can improve outcomes for people with FAP. A liver transplant is believed to be one of the first FAP research breakthroughs to increase FAP survival rates.

Because FAP affects every person differently, it can be challenging to make broad predictions about outcomes after a liver transplant. While the procedure can generally help slow disease progression, it can’t reverse damage that has already accrued, so FAP symptoms that are present before the transplant will typically persist  after the procedure.

It’s therefore generally accepted that a liver transplant is most effective when given as early as possible in the course of the disease, when organ damage and disease symptoms are less severe.

A liver transplant, however, shouldn’t be viewed as a definitive cure for FAP. People with FAP who receive a transplant can still experience disease progression and develop new FAP complications, such as heart issues or eye problems. Thus, these patients will continue to require lifelong medical care and monitoring following a liver transplant.

Some studies have reported that around 85% of FAP patients who have a liver transplant survive at least five years, while roughly 73% live at least 10 years after the procedure. However, survival seems to be even greater for those carrying Val30Met, the most common FAP-causing mutation, in whom a liver transplant has been associated with a 10-year survival rate of 100%.

A significant body of evidence similarly indicates that patients with Val30Met tend to have better outcomes from liver transplant than those with other disease-causing mutations. Other factors, such as pre-transplant nutritional and clinical status, can also affect liver transplant outcomes in people with FAP.

Patients are advised to talk to their healthcare team in depth about the benefits and risks of liver transplant for people with FAP to make an informed decision about whether a liver transplant is right for them.

These discussions should also include the potential risks and benefits of the several FAP approved medications that may be alternatives to liver transplant for FAP. Early evidence has suggested that some of these therapies may prolong survival, although some may be less effective at slowing progression of nerve and heart damage.

How is the operation performed?

When a person with FAP, along with their medical team, decides on a liver transplant, the initial and often challenging step is in finding a matching healthy donor liver. In the U.S., most donated livers come from deceased donors, though it’s also feasible to use a liver from a living donor. In those cases, only a portion of the donor’s liver is transplanted, but it is able to regenerate and develop into a fully functional liver within the recipient’s body.

The liver transplant surgery itself is a complex procedure that usually lasts between six and 12 hours. The patient is put under general anesthesia and surgeons make a long cut in the abdomen to access the liver. They then carefully remove the patient’s liver and put in the donor’s liver, attaching it to major blood vessels and other important connections before closing the incision.

After the surgery, patients will usually stay in a hospital for a few weeks and continue their recovery at home, undergoing frequent monitoring to ensure the liver is healthy and working properly.

While the recovery time can vary widely depending on several health factors, most patients can expect to resume normal or near normal activities six to 12 months after the procedure.

Still, patients will typically require lifelong post-transplant care, including immunosuppressive medications to prevent the body from rejecting the transplanted organ and frequent checkups to monitor liver function.

Potential complications of liver transplant

With modern medical techniques, about 85 to 90% of liver transplants are successful, meaning that most people who undergo the procedure make a full recovery after transplant. But, as with any major medical operation, there are possible risks to getting a liver transplant.

Short-term risks associated with the surgery itself include:

• blood clots, especially if the surgery lasts a long time
• excessive bleeding
• damage to bile ducts, or the tubes that carry a digestive fluid called bile from the liver to the intestines
• liver failure, if the donated liver fails to function properly once implanted, which occurs in about 5% of cases and requires that patients receive a new donor liver as soon as possible.

Acute organ rejection occurs in up to half of liver transplant cases, most commonly in the first six weeks after surgery. Signs of rejection may include elevated blood levels of liver enzymes, fever, nausea, headache, and reduced appetite, along withs signs of liver disease such as itchy skin and yellowing of the skin and/or white parts of the eyes, called jaundice.

In most cases, acute liver rejection can be managed with adjustments in immunosuppressive treatment, but about 5% of transplant recipients develop chronic rejection despite treatment, which can lead to liver failure in the long term.

Beyond the risks associated with liver transplant itself, the long-term use of immunosuppressive medications in transplant recipients increases the risk of certain health problems including:

• infections
• high blood pressure
• type 2 diabetes
• kidney disease
• certain cancers.

FAP News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.