Patisiran treatment in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy after liver transplantation

Am J Transplant. 2022 Jun;22(6):1646-1657. doi: 10.1111/ajt.17009. Epub 2022 Mar 26.


Hereditary transthyretin-mediated (hATTR) amyloidosis, or ATTRv amyloidosis, is a progressive disease, for which liver transplantation (LT) has been a long-standing treatment. However, disease progression continues post-LT. This Phase 3b, open-label trial evaluated efficacy and safety of patisiran in patients with ATTRv amyloidosis with polyneuropathy progression post-LT. Primary endpoint was median transthyretin (TTR) reduction from baseline. Twenty-three patients received patisiran for 12 months alongside immunosuppression regimens. Patisiran elicited a rapid, sustained TTR reduction (median reduction [Months 6 and 12 average], 91.0%; 95% CI: 86.1%-92.3%); improved neuropathy, quality of life, and autonomic symptoms from baseline to Month 12 (mean change [SEM], Neuropathy Impairment Score, -3.7 [2.7]; Norfolk Quality of Life-Diabetic Neuropathy questionnaire, -6.5 [4.9]; least-squares mean [SEM], Composite Autonomic Symptom Score-31, -5.0 [2.6]); and stabilized disability (Rasch-built Overall Disability Scale) and nutritional status (modified body mass index). Adverse events were mild or moderate; five patients experienced ≥1 serious adverse event. Most patients had normal liver function tests. One patient experienced transplant rejection consistent with inadequate immunosuppression, remained on patisiran, and completed the study. In conclusion, patisiran reduced serum TTR, was well tolerated, and improved or stabilized key disease impairment measures in patients with ATTRv amyloidosis with polyneuropathy progression post-LT ( NCT03862807).

Keywords: clinical research/practice; clinical trial; liver allograft function/dysfunction; liver transplantation/hepatology; molecular biology: small interfering RNA; neurology; patient survival; pharmacology.

Publication types

  • Clinical Trial, Phase III
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Neuropathies, Familial* / complications
  • Amyloid Neuropathies, Familial* / drug therapy
  • Amyloid Neuropathies, Familial* / surgery
  • Humans
  • Liver Transplantation*
  • Polyneuropathies* / drug therapy
  • Polyneuropathies* / etiology
  • Prealbumin / therapeutic use
  • Quality of Life
  • RNA, Small Interfering


  • Prealbumin
  • RNA, Small Interfering
  • patisiran

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related

Associated data