To report our experience with transthyretin (TTR) knockdown therapy in patients with hereditary TTR amyloidosis (hATTR) with progressive disease despite liver transplantation.

Patients with hATTR amyloidosis, especially those with non V30M mutations, can continue to have disease progression and reduced survival despite early liver transplant. This is thought to be related to wild type ATTR deposition (wtATTR). Newly approved TTR knockdown therapies (Patisiran and Inotersen), significantly reduce the production of both mutated ATTR (mATTR) and wtATTR^1,2.

Two patients with hATTR amyloidosis who continued to have disease progression despite liver transplantation were started on Inotersen.

The first patient is a 49 year-old man with TTR-Arg50 mutation and the second patient is 64 year-old man with T32C TTR mutation. Both patients undergone liver transplantation 2 years after symptoms onset and both had symptom stabilization lasting only for 2 years, prior to disease progression. Both patients have now been started on Inotersen with stabilization of neurological examination in one, while the second has been on the drug for one month. Both patients will be formally evaluated prior to presentation of the abstract (length of follow-up would be 12 months and 6 months respectively).

Progression of disease following liver transplant in patients with hATTR amyloid neuropathy is likely related to ongoing wtATTR deposition and novel ATTR knockdown therapies may present an attractive means for global ATTR suppression in these patients.  We present 2 representative patients that depict this clinical conundrum.