Progression of cardiac amyloid deposition in hereditary transthyretin amyloidosis patients after liver transplantation

Abstract

It has been hypothesized that transthyretin (TTR) amyloidosis may progress after orthotopic liver transplantation (OLT) as a result of continued amyloid fibril synthesis and deposition from normal TTR. To test this hypothesis amyloid fibrils were isolated from cardiac tissues of three patients who died 1(1/2) to 5(1/2) years after OLT: two with Val30Met and one with Thr60Ala TTR. The ratio of variant to normal TTR in each case was determined and compared with the ratio of variant to normal in cardiac tissues from seven patients who died with TTR amyloidosis but who had not had liver transplantation. Tissues from patients with TTR amyloidosis without OLT included three with Val30Met, two with Thr60Ala, one with deltaVal122, and one with Val122Ile. All tissues from patients without OLT had greater amounts of variant TTR than normal TTR except for the Val122Ile in which the ratio was 50:50. The overall median variant to normal ratio was 60:40 with a range of 50-70% variant. In contrast, the mean percentage of variant TTR in the three tissues from patients after OLT was 25% (range 20-35). These data are consistent with the continued deposition of normal TTR in cardiac tissue after liver transplantation.

Current and future treatment of amyloid neuropathies

“…Current & future treatment of amyloid neuropathies Review informahealthcare.com neuropathy which has been reported in 20 [31] to 25% of patients after LT [9] could be due to continuation of deposit of amyloid from wild-type TTR [16,32]. Serial assessment of MIBG after LT showed stable values with a mid-term follow up [33] while cardiac thickening by amyloid deposits is commonly worsening over time [34] in favor of myocardial deposit.…”

Emerging treatments for amyloidosis

“…35 In other mutations, and in older patients, outcomes are less favorable, and may reflect postoperative amyloid cardiomyopathy. 36 This is thought to be due to the deposition of wt TTR on a template of preexisting cardiac amyloid derived from variant proteins. 37 The need for better therapies has resulted in the development of a number of novel strategies, and some of these have been assessed in clinical trials.…”

Amyloidose des Herzens

“…Zu den systemisch auftretenden erblichen Amyloidosen zählen außerdem die Fibrinogen-α (AFib)-, Apolipoprotein-AI (AApoAI)-und Lysozym (ALys)-assoziierten Amyloidosen, die eine Rarität darstellen [7,8,34]. Bei folgenden hereditären Amyloidosen wurde ein Befall des Herzens beschrieben: AApoAI-Amyloidose [10,11,29]; AFib-Amyloidose [28] und ATTR-Amyloidose [1,3,24,33].…”