Cardiac involvement worsens survival after liver transplant in ATTR amyloidosis

A 30-year global registry study in eGastroenterology found that phenotype strongly shapes long-term outcomes after liver transplant for hereditary transthyretin amyloidosis. Cardiac involvement was the clearest predictor of poorer survival, while renal involvement alone did not rule out transplant benefit.

Why it matters: - The study helps define which ATTR amyloidosis patients are most likely to gain long-term benefit from liver transplant. - Cardiac involvement carried the worst survival signal, which is important as gene-silencing and gene-editing therapies have reduced the role of transplant. - The findings offer a benchmark for comparing liver transplantation with newer treatments in hereditary transthyretin amyloidosis.

What happened: - Researchers led by Dr. Henryk Wilczek analyzed 1,762 patients who underwent isolated liver transplantation between 1990 and 2012. - The data came from the Familial Amyloidotic Polyneuropathy World Transplant Registry and covered 82 centers in 21 countries. - The study was published in eGastroenterology. - Patients were grouped by organ involvement before transplant: polyneuropathy only, cardiac plus polyneuropathy, renal plus polyneuropathy, and cardiorenal plus polyneuropathy.

The details: - Median survival after liver transplant was 20.4 years. - The 25-year survival rate was 32.4%. - Survival differed by phenotype. - Patients with cardiac plus polyneuropathy had median survival of 15.2 years. - Patients with cardiorenal plus polyneuropathy had median survival of 20.8 years. - Patients with polyneuropathy only had median survival of 22.7 years. - Cardiac involvement emerged as the strongest adverse prognostic factor. - Cardiac disease doubled mortality risk in univariable analysis and remained significant after adjustment. - Older age at transplantation increased mortality risk. - Longer disease duration before transplant worsened outcomes. - Poorer nutritional status, measured by modified body mass index, predicted worse survival. - Non-V30M variants were linked to poorer prognosis. - Each additional year of age at transplantation raised mortality risk by about 6%. - Better nutritional status independently improved survival.

Between the lines: - The results support a more selective transplant strategy in ATTR amyloidosis. - Cardiac involvement should weigh heavily in patient selection because it appears to drive long-term risk. - Renal involvement alone does not appear to be a reason to exclude transplant candidacy. - Earlier referral may matter because age, disease duration, and nutrition all influenced survival. - Post-transplant follow-up may need to focus on autonomic neuropathy, which worsened earlier than peripheral neuropathy or other organ involvement. - The pattern was especially clear in patients with the polyneuropathy-only phenotype. - Worsening autonomic symptoms may serve as an early warning sign for disease progression and the possible need for adjunct pharmacotherapy.

What’s next: - The study suggests transplant programs may use phenotype to refine selection in the era of RNA-silencing drugs and CRISPR-based gene editing. - Long-term registry data may help clinicians compare transplant outcomes with emerging therapies that target transthyretin production. - Care teams are likely to place more emphasis on cardiac evaluation, nutrition, and autonomic monitoring before and after transplant.

The bottom line: - Liver transplant can still deliver decades of survival in hereditary transthyretin amyloidosis, but patients with cardiac involvement face the poorest odds.