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 va riant TTR-associated familial amyloid polyneuropathy (FAP), The effect of OLT on FAP-related cardiac amyloid is of particular interest becau se wild-type TTR can itself be deposited as senile cardiac amyloid, Me thods. 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 pl asma TTR before and after OLT, Results. Cardiac amyloidosis progressed rapidly in three FAP patients (TTR Pro52 and Thr84 mutations) after O LT, even though the deposits elsewhere had stabilized or regressed. Re sults of echocardiography improved in three transplant patients with T TR Met30 and remained normal in seven other patients. Plasma TTR level s were altered substantially after OLT, but they did not reflect the c ardiac findings. Conclusions. Although amyloid deposition in FAP is ge nerally inhibited after OLT, cardiac amyloidosis can be exacerbated, p robably due to enhanced deposition of wild-type TTR on a template of a myloid derived from variant TTR, The phenomenon may be mutation-depend ent, These findings suggest that amyloid formation de novo and its sub sequent accumulation can be promoted by different factors, which may b e organ-specific.