Liver transplantation may be helpful for some patients with hereditary ATTR amyloidosis, mainly for patients with the Val30Met mutation.
All the TTR in the blood, which forms the amyloid deposits everywhere except in the eye and the blood vessels around the brain, is made in the liver. Liver transplantation is therefore a treatment option for some patients with hereditary ATTR amyloidosis. The liver which forms the abnormal, 'variant' TTR is removed and replaced by a donor liver making normal, 'wild type' TTR. The aim is to prevent the formation of further amyloid deposits by reducing the supply of the amyloidogenic precursor TTR.
Liver transplantation has been performed in hundreds of patients with hereditary ATTR amyloidosis around the world. In many cases this has been successful, leading to stabilization of disease. Success is greatest when transplantation is performed:
- Early in the disease before there has been too much damage to the nerves or the heart
- In younger patients
- In patients with the TTR Val30Met mutation
Unfortunately, in some patients, amyloid deposits in the heart have continued to progress even after transplantation. It seems that the abnormal TTR fibrils which formed amyloid deposits before the liver transplantation act as a template encouraging deposition of normal TTR as amyloid. Thus, the normal TTR protein (wild type TTR) produced by the new liver builds up on top of the existing amyloid deposits containing the abnormal TTR. This problem has appeared most often in older patients with mutations other than Val30Met.
Liver transplantation is not a treatment for wild type ATTR amyloidosis, because the cardiomyopathy continues to progress due to continued deposition of wild type TTR in the heart.