Purpose of review: Familial amyloid polyneuropathy (FAP) associated with mutations in the gene for transthyretin is a rare, progressively disabling and ultimately fatal inherited disease. Transthyretin is produced predominantly in the liver, and orthotopic liver transplantation (OLT) eliminates more than 95% of variant amyloidogenic transthyretin from the circulation. Liver transplantation remains the only potentially curative treatment in this disorder, but many recent studies have suggested that outcome following transplantation may be poorer than previously considered in some groups of FAP patients.
Recent findings: We review here the available data on the use and clinical outcome of OLT in patients with FAP, and consider the significance of particular mutations and cardiac amyloid involvement. The practice of combined organ transplants and domino liver transplantation is also reviewed.
Summary: Published data generally support OLT as a treatment for FAP, particularly in younger patients with the most prevalent transthyretin (TTR) Met30 variant, who have mild symptoms. Although excellent outcomes have been reported, including improvement in autonomic and to a lesser extent peripheral nerve function coupled with regression of visceral amyloid deposits, the results of OLT are influenced by many factors that include properties of particular transthyretin variants, nutritional status, age, severity of neuropathy and cardiac amyloid involvement. Paradoxical acceleration of transthyretin amyloid deposition following OLT may occur in the heart and certain other sites in some patients. The combination of kidney or heart transplantation with OLT may occasionally be appropriate. The long-term outcome of patients with FAP who have undergone OLT, and recipients of FAP domino liver transplants, remain to be determined.