Also in patients with systemic hereditary ATTR amyloidosis the supply of new building bricks can be stopped in order to prevent further accumulation of amyloid deposits. The only currently available method to do this is to replace the organ in which about 95-99% of the mutated TTR, the building brick, is made by an organ that does not produce this mutated TTR. This organ is the liver. In hereditary ATTR amyloidosis liver transplantation (if necessary and if possible) can be considered, a procedure that has been performed for this reason in Groningen since 1995. However, this procedure has major risks and these risks increase progressively when amyloid deposition is severe, extensive, and vital organs are involved. This is especially true for the heart that should be able to permit major surgery, but also the gastrointestinal tract (leading to severe loss of body weight) or autonomic failure (severe orthostatic hypotension or problems with emptying of the urine bladder leading to a high risk of ascending urinary tract infections). Balancing of risks and benefits of liver transplantation in the individual patient is a difficult process in which all members of the transplantation team are involved.
It should, however, be completely clear that a minimal amount (1-5%) of TTR is produced outside the liver, namely by the retina (responsible for the vitreous opacities) and by the plexus choroideus (vascular tangle located in the middle of the brain that produces cerebral fluid in which TTR is present and this TTR can be deposited as amyloid in the meninges). This means that liver transplantation can not prevent (further) deposition of amyloid in the eyes and meninges.
The expectation was in the beginning of the nineties that after liver transplantation further growth of amyloid in the body stops. Gradually the long-term (5-10 years) results of liver transplantation become available. When the liver is transplanted early in the course of the disease the hope of stopping or considerably slowing down the disease seems to be justified. However, in progressive ATTR amyloidosis liver transplantation often cannot stop the disease anymore. In these cases it appears that the wild type (i.e. non-mutated) TTR can be forced to be folded is such a different way that it can be used as building brick and amyloid deposition will grow consequently. This mechanism seems to be present most frequently in the so-called non-TTRmet30 types. Hopefully more information about these phenomena will become available in the next years. In this respect it is worth to mention that also the normal, wild type TTR can be deposited as amyloid in the form of the so-called senile systemic ATTR amyloidosis. Until recently this seemed to be a form of amyloidosis only seen in old age and leading to only minimal clinical signs, such as an often indolent or slowly progressive cardiomyopathy.
Liver transplantation is therefore not the definite and final solution for hereditary ATTR amyloidosis. Currently the expectations are that new drugs may be developed that will modify or influence TTR in the circulation in such a way that it cannot be used anymore as building brick for further amyloid deposition. Until our hope that these drugs will become available is justified, liver transplantation is the only possible treatment and should be considered in the individual patient as early in the disease as possible: The good period to have a transplant should not have passed away and the risks should be acceptable. This timing is even more important because the waiting list for transplantation is long (currently at least one year and often longer).
Finally the vitreous opacities. The only way to get rid of these is by surgery. Because the production of amyloid precursor does not stop and therefore amyloid deposition will continue, these opacities will come back an will necessitate repeated surgery when the sight becomes disturbed again.