In patients with hereditary transthyretin amyloidosis (hATTR), first-line treatment with tafamidis is associated with improved overall survival but poor stabilization of cardiac and neurologic statuses compared to those following liver transplantation, according to findings from a monocentric, retrospective cohort analysis published in Amyloid.

A point mutation in the transthyretin (TTR) gene leads to hATTR, an autosomal dominant disease. In patients with hATTR, the circulating mutated TTR protein that is generated by the liver misfolds and triggers the deposition of amyloid fibers in target organs such as the heart and the peripheral nervous system.

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The researchers sought to compare treatment with tafamidis—a TTR tetramer stabilizer—with liver transplantation in patients with hATTR. The strategies were compared via the use of a propensity score and a competing risk analysis for 3 endpoints:

  • All-cause mortality
  • Cardiac worsening (heart failure or cardiovascular death)
  • Neurologic deterioration (based on the PolyNeuropathy Disability [PND] score).

The current study was initiated by investigators from the French Referral Center for Familial Amyloid Polyneuropathy and Other Rare Peripheral Neuropathies. Participants were identified between January 1993 and May 2018 from the registry of the French National Reference Center.

Study inclusion criteria were (1) biopsy-proven amyloidosis due to a transthyretin variant with a positive finding of an amyloidogenic TTR point mutation and (2) first-line treatment with tafamidis or liver transplantation. Double transplant patients (ie, those receiving a liver and kidney or heart transplant) were excluded.

The study evaluated 345 consecutive patients with hATTR—216 in the liver transplantation group and 129 in the tafamidis group. The median participant age was 53 years (range, 38 to 64 years). Overall, 222 patients were male, and 223 carried the V30M TTR mutation. The median follow-up was 68 months (range, 37 to 105 months).

The researchers matched 144 patients, with 72 individuals in each group (ie, 72 pairs) eligible for comparison. The median age of those in the matched cohort was 54 years (range, 40 to 62 years).

Results showed that participants treated with tafamidis experienced significantly longer overall survival than those who received liver transplantation (hazard ratio [HR], 0.35; P =.032). In contrast, tafamidis-treated participants had a 3-fold increased risk of cardiac worsening (HR, 3.00; 95% CI, 1.35-6.68; P =.0071) and a 7.1-fold increased risk of neurologic worsening based on PND score (HR, 7.20; 95% CI, 3.14-16.50; P <.001).

“This hypothesis-generating analysis pleads for future studies that will assess the comparative efficacy of the anti-amyloid therapies,” the authors concluded.


Socie P, Benmalek A, Cauquil C, et al. Comparison between tafamidis and liver transplantation as first-line therapy for hereditary transthyretin amyloidosis. Amyloid. Published online February 16, 2023. doi:10.1080/13506129.2023.2177986