Clinical symptomatic de novo systemic transthyretin amyloidosis 9 years after domino liver transplantation

Barreiros, Ana Paula; Geber, Christian; Birklein, Frank; Galle, Peter R.; Otto, Gerd

doi:10.1002/lt.21928

Cited by 42 publications

(34 citation statements)

References 3 publications

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“…Recently, 3 cases of the transmission of systemic TTR amyloidosis were published. [9][10][11] Surprisingly, these cases were diagnosed after a follow-up period shorter than that previously thought necessary. The first alert in the literature was raised by Stangou and Heaton, 9 who described the case of a 55-year-old patient with clinical polyneuropathy confirmed by EMG and nerve biopsy 8 years after DLT.…”

Section: Discussionmentioning

confidence: 84%

“…Recently, a new case was reported 9 years after DLT. 11 Once again, however, sural nerve biopsy was not performed. Finally, at an international neurological meeting, the French Reference Center for FAP recently reported the results of a series involving 3 proven cases of amyloid neuropathy.…”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11] It is not known why these patients develop symptoms earlier than patients with FAP, although several factors may be related to this evolution. For instance, the recipient's age has a possible role.…”

Section: Discussionmentioning

confidence: 99%

“…However, there are at least 3 case studies describing the transmission of systemic TTR amyloidosis by means of DLT. [9][10][11] These reports have led to concerns in the literature about the real long-term risks of DLT. 12,13 Most research to date has been in the form of case reports or studies focused only on pathological or neurological data.…”

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confidence: 99%

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Risk of transmission of systemic transthyretin amyloidosis after domino liver transplantation

et al. 2010

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Recent reports of the transmission of systemic transthyretin (TTR) amyloidosis after domino liver transplantation (DLT) using grafts from patients with familial amyloid polyneuropathy (FAP) have raised concerns about the procedure. The aim of this study was to evaluate the transmission incidence of systemic TTR amyloidosis after DLT with a complete clinical, neurological, and pathological assessment. At our institution, DLT has been performed 31 times with livers from patients with FAP. Seventeen of the 19 patients still alive in 2008 agreed to enter the study. This cross‐sectional study of this cohort of patients included clinical assessments, rectal biopsy, and electroneuromyography (as well as sural nerve biopsy when it was indicated). The mean follow‐up at the time of the study was 62.6 ± 2.9 months. Clinically, 3 patients complained of weak dysesthesia. When a focused study was performed, 8 patients reported some kind of neurological and/or gastrointestinal disturbance. Six of the rectal biopsy samples showed amyloid deposits (TTR‐positive). Electromyography (EMG) showed signs of mild sensorimotor neuropathy in 3 cases and moderate to severe sensorimotor neuropathy in 1 case. Only 2 of the 4 patients with EMG signs of polyneuropathy showed amyloid deposits in their rectal biopsy samples. Sural nerve biopsy revealed amyloid deposits (TTR‐positive) in all 4 patients with EMG signs of polyneuropathy. Two patients with normal EMG findings had TTR‐positive amyloid deposits in their sural nerve biopsy samples. In conclusion, de novo systemic amyloidosis after DLT may be more frequent and appear earlier than was initially thought. In our opinion, however, the graft shortage still justifies DLT in selected patients, despite the risk of de novo systemic amyloidosis. Sural nerve biopsy with EMG and clinical correlation is mandatory for confirming the disease. Indeed, other causes of neuropathy should be excluded. Liver Transpl 16:1386–1392, 2010. © 2010 AASLD.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Risk of transmission of systemic transthyretin amyloidosis after domino liver transplantation

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“…Amyloid deposition from the implanted liver is thought to occur very slowly. Rare cases of recurrence of amyloid deposition in the liver recipient have been reported 8-10 years after the transplant [143]- [145].…”

Section: Combined Heart and Liver Transplant In Attr Cardiac Amyloidosismentioning

confidence: 99%

Treatment of End Stage Heart Failure Related to Cardiac Amyloidosis

Hasin¹,

Raichlin²,

Dispenzieri³

et al. 2013

Amyloidosis

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The pathological and biochemical identification of possible seed‐lesions of transmitted transthyretin amyloidosis after domino liver transplantation

Yoshinaga

Yazaki

Sekijima

et al. 2016

The Journal of Pathology CR

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The most serious issue in domino liver transplantation (DLT) using liver grafts from patients with transthyretin (TTR)‐related familial amyloid polyneuropathy (FAP) is the development of iatrogenic transmitted amyloidosis (de novo amyloidosis) in DLT‐recipients. However, little is known regarding the mechanisms of the initial stage of amyloid formation in these recipients. We detected initial lesions (possible seed‐lesions) of this iatrogenic amyloidosis in two recipients following liver grafting from FAP patients. Patient 1 underwent DLT at age 65 from an FAP patient with a Val30Met TTR variant and patient 2 received DLT from an FAP patient with a Val30Leu TTR variant at age 32. Patient 2 was started on diflunisal administration from 4 years after DLT. While neither patient had symptoms of FAP, small amyloid deposits were detected on the gastroduodenal mucosae 14 months and 12 years after DLT in patient 1 and patient 2, respectively. The amyloid was analyzed using a laser microdissection system and tandem mass spectrometry. Biochemical analysis indicated that the amyloid was composed mostly of variant TTR produced from the transplanted liver in both patients. In patient 1, wild‐type TTR amyloid was detectable in the duodenal mucosa obtained 2 years after DLT. This is the first study to successfully capture the pathological and biochemical features of initial‐stage amyloid lesions in DLT recipients. The findings clearly indicate that amyloid deposition can start by deposition of variant TTR followed by deposition of wild‐type TTR, and blocking of amyloid seed formation from variant TTR may be a key to prevent or delay the development of DLT‐associated amyloidosis.

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Clinical symptomatic de novo systemic transthyretin amyloidosis 9 years after domino liver transplantation

Cited by 42 publications

References 3 publications

Risk of transmission of systemic transthyretin amyloidosis after domino liver transplantation

Risk of transmission of systemic transthyretin amyloidosis after domino liver transplantation

Treatment of End Stage Heart Failure Related to Cardiac Amyloidosis

The pathological and biochemical identification of possible seed‐lesions of transmitted transthyretin amyloidosis after domino liver transplantation

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