A narrative review and expert recommendations on the assessment of the clinical manifestations, follow-up, and management of post-OLT patients with ATTRv amyloidosis.
Carlos CasasnovasLaura LladóCristina BorracheroPatricia Valentina Pérez-SantamaríaFrancisco Muñoz-BeamudInés Asunción Losada-LópezMaria Carme Baliellas-ComellasJuan González-MorenoPublished in: Therapeutic advances in neurological disorders (2023)
Orthotopic liver transplantation (OLT) was the first treatment able to modify the natural course of hereditary transthyretin (ATTRv) amyloidosis, which is a rare and fatal disorder caused by the accumulation of misfolded transthyretin (TTR) variants in different organs and tissues and which leads to a progressive and multisystem dysfunction. Because the liver is the main source of TTR, OLT dramatically reduces the production of the pathogenic TTR variant, which should prevent amyloid formation and halt disease progression. However, amyloidosis progression may occur after OLT due to wild-type TTR deposition, especially in the nerves and heart. In this review, we discuss the disease features influencing OLT outcomes and the clinical manifestations of ATTRv amyloidosis progression post-OLT to improve our understanding of disease worsening after OLT and optimize the follow-up and clinical management of these patients. By conducting a literature review on the PubMed database, we identified patient characteristics that have been associated with worse post-OLT outcomes, including late-onset V50M and non-V50M variants, age >40 years, long disease duration, advanced neuropathy and autonomic dysfunction, and malnutrition. Regarding post-OLT mortality, deaths occurring within the first year after OLT were mainly associated with fatal graft complications and infectious diseases, whereas cardiovascular-related deaths usually occurred later. Considering the diverse clinical manifestations of ATTRv amyloidosis progression post-OLT, including worsening neuropathy and/or cardiomyopathy, autonomic dysfunction, and oculoleptomeningeal involvement, we present advice on the most relevant tests for assessing disease progression post-OLT. Finally, we discuss the use of new therapies based on TTR stabilizers and TTR mRNA silencers for the treatment of ATTRv amyloidosis patients post-OLT.
Keyphrases
- late onset
- end stage renal disease
- wild type
- multiple myeloma
- heart failure
- chronic kidney disease
- ejection fraction
- newly diagnosed
- multiple sclerosis
- case report
- heart rate
- prognostic factors
- early onset
- skeletal muscle
- type diabetes
- patient reported outcomes
- adipose tissue
- genome wide
- electronic health record
- binding protein
- clinical evaluation