Liver transplantation and transthyretin amyloidosis

Liver transplantation as a specific treatment of transthyretin amyloidosis was first performed in 1990. The rationale for this treatment was that removal of the source (liver) of the amyloid precursor protein (mutated transthyretin) would stop progression of the disease. Indeed, after orthotopic liver transplantation (OLT), mutant transthyretin (TTR) is rapidly cleared from circulation. In the last 20 years, >2000 familial amyloidotic polyneuropathy (FAP) patients have received liver transplants. For these patients, prospective monitoring has shown prolongation of life compared with FAP patients who have not undergone liver transplantation. The most favorable results have been for FAP patients with the Val30Met TTR mutation. Less favorable results have been seen for patients with other TTR mutations where progression of amyloid tissue deposition has been documented as the result of amyloid fibril formation from normal (wild-type) TTR. Although it is obvious that OLT has benefited many FAP patients, there remains a need for further therapies. Muscle Nerve47: 157-162, 2013