Progressive cardiac amyloidosis following liver transplantation for familial amyloid polyneuropathy: implications for amyloid fibrillogenesis.

Background: Circulating transthyretin (TTR) is derived from the liver, and orthotopic liver transplantation (OLT) is widely performed for variant TTR-associated familial amyloid polyneuropathy (FAP). The effect of OLT on FAP-related cardiac amyloid is of particular interest because wild-type TTR can itself be deposited as senile cardiac amyloid.

Methods: Serial echocardiography was performed in 20 FAP patients, 14 of whom underwent OLT, and 10 other liver transplant patients. Follow-up included serum amyloid P component scintigraphy and measurement of plasma TTR before and after OLT.

Results: Cardiac amyloidosis progressed rapidly in three FAP patients (TTR Pro52 and Thr84 mutations) after OLT, even though the deposits elsewhere had stabilized or regressed. Results of echocardiography improved in three transplant patients with TTR Met30 and remained normal in seven other patients. Plasma TTR levels were altered substantially after OLT, but they did not reflect the cardiac findings.

Conclusions: Although amyloid deposition in FAP is generally inhibited after OLT, cardiac amyloidosis can be exacerbated, probably due to enhanced deposition of wild-type TTR on a template of amyloid derived from variant TTR. The phenomenon may be mutation-dependent. These findings suggest that amyloid formation de novo and its subsequent accumulation can be promoted by different factors, which may be organ-specific.