Amyloid Polyneuropathy and Myocardial Amyloidosis 10 Years after Domino Liver Transplantation from a Patient with a <i>Transthyretin</i> Ser50Arg Mutation

Abstract

A 54-year-old man with polycystic liver disease received a domino liver transplantation (DLT) from a patient of hereditary ATTR amyloidosis with the transthyretin Ser50Arg mutation. Ten years after transplantation, he felt a slight numbness in his toes, and cardiac amyloidosis was simultaneously suspected upon a heart function evaluation. Biopsy specimens from the myocardium revealed transthyretin amyloidosis with the Ser50Arg mutation. Oral tafamidis therapy has inhibited the progression of neurological and cardiovascular symptoms this far. We herein report this first case of amyloid polyneuropathy and myocardial amyloidosis after DLT from hereditary ATTR amyloidosis with a transthyretin Ser50Arg mutation and discuss similar cases of other mutations.

Treatment With Diflunisal in Domino Liver Transplant Recipients With Acquired Amyloid Neuropathy

“…Another patient who was given a trial of diflunisal needed their treatment to be stopped because of worsening heart failure [ 26 ]. Compassionate treatment with tafamidis was initiated in another patient with AAN, who remained stable for 2 years [ 27 ]. Prophylactic use of diflunisal or tafamidis has also been proposed in DLT recipients [ 32 ].…”

“…These results are similar to those reported in the clinical trial by Berk et al, in which 29.7% of patients with hATTR presented neurological stability (increase <2 points on the NIS +7 scale) after 2 years of treatment with diflunisal versus only 9.4% in the placebo group. It may be that a subgroup of patients responds to treatment and remains stable during the first years of treatment, as Bourque et al [ 25 ] and Matsushima et al [ 27 ] described. Analyzing the predictive factors of long-term response to diflunisal may be of benefit.…”

“…Liver re-transplantation, which can stabilize or even improve symptoms [ 11 , 12 , 24 ], may be considered but is often limited by the patient’s age or comorbidities. Regarding medical treatment, case reports have suggested that treatment with TTR stabilizers (diflunisal or tafamidis) can produce clinical stabilization in some cases [ 25 – 27 ]. To date, there have been no data from case series with long-term follow-up of the effects of diflunisal or other treatments in these patients.…”

Temporal Change in Longitudinal Strain After Domino Liver Transplantation With Liver Grafts Explanted From Patients With Hereditary Amyloidogenic Transthyretin Amyloidosis

“…In contrast, there are only a few case reports on ATTR-CM after DLT. 5 , 6 , 14 Therefore, the time-dependent changes in cardiac function after DLT have not been fully clarified. The present study showed that LVEF, the E/A ratio, the E/e’ ratio, e’ wave velocity, LAVI, and TRV did not differ significantly between the pre- and post-DLT periods, indicating that LV systolic and diastolic function was preserved in the long term after DLT.…”

Transthyretin amyloidosis with cardiomyopathy after domino liver transplantation: Results of a cross-sectional study

“…The first one revealed ATTR-CM at autopsy in a patient who died of Burkitt's lymphoma 8 years after a DLT from a patient with a Tyr114Cys mutation. 7 Three other case reports showed in vivo ATTR cardiac deposition after DLT from patients with the mutation Val71Ala, 8 Serg50Arg, 9 and Val30Met 10 at 5, 10, and 16 years after DLT, respectively. The development of ATTR-CM has a significant impact on outcomes.…”