Pathological changes long after liver transplantation in a familial amyloidotic polyneuropathy patient

Abstract

Liver transplantation (LT) reportedly prolongs the survival of patients with familial amyloidotic polyneuropathy (FAP), a fatal hereditary systemic amyloidosis caused by mutant transthyretin (TTR). However, what happens in systemic tissue sites long after LT is poorly understood. In the present study, we report pathological and biochemical findings for an FAP patient who underwent LT and died from refractory ventricular fibrillation more than 16 years after FAP onset. Our autopsy study revealed that the distributions of amyloid deposits after LT were quite different from those in FAP amyloidogenic TTR V30M patients not having had LT and seemed to be similar to those observed in senile systemic amyloidosis (SSA), a sporadic systemic amyloidosis derived from wild-type (WT) TTR. Our biochemical examination also revealed that this patient's cardiac and tongue amyloid deposits derived mostly from WT TTR. We propose that FAP patients after LT may suffer from SSA-like WT TTR amyloidosis in systemic organs.

Ocular Manifestations and Therapeutic Options in Patients with Familial Amyloid Polyneuropathy: A Systematic Review

“…Liver transplantation removes the main source of mutated TTR, resulting in the fast decline of its concentration to levels around 1%. Thus it stops the progression of neurological symptoms [ 34 ] and promotes patient survival, as long as it is performed at an early stage [ 3 , 6 ].…”

“…Obayashi et al [ 3 ] described the disease course in a 28-year-old patient, transplanted two years after the disease onset. The patient presented pupil amyloid deposition and vitreous opacities 10 years and 13 years, respectively, after the transplantation.…”

“…This condition may be primary in origin, very often hereditary and leading to familial amyloid polyneuropathy (FAP), or secondary to chronic inflammatory diseases and causing a sporadic form of the disease, senile systemic amyloidosis (SSA) [ 3 , 4 ]. The latter is age related and has a milder clinical picture, mainly affecting the heart [ 5 , 6 ].…”

Changes in pathological and biochemical findings of systemic tissue sites in familial amyloid polyneuropathy more than 10 years after liver transplantation

“…We used the FAP clinical score to assess clinical symptoms 16. We previously reported details of cases LT117 and LT3 18. For analysing the truncated form of TTR in amyloid, we also employed formalin-fixed autopsy or biopsy specimens from additional 18 FAP patients with heterozygous for the ATTR V30M (see online supplementary table S1).…”

Involvement of Macrophages in the Pathogenesis of Familial Amyloid Polyneuropathy and Efficacy of Human iPS Cell-Derived Macrophages in Its Treatment

“…Alternatively, for the purpose of removing mutant TTR from blood, liver transplantation (LT) has been performed as a FAP treatment, and shown success in prolonging survival of FAP ATTR V30M patients [ 17 , 18 ]. Importantly, the loss of already deposited TTR-derived amyloid fibrils was observed in several organs after LT [ 19 , 20 ]. This suggests that, if supply of mutated TTR declines, FAP patients are innately capable of treating mutated-derived TTR amyloid fibrils that are already present.…”