Cardiac problems are the leading cause of death among transthyretin familial amyloid polyneuropathy (ATTR, also called FAP) patients who have had a liver transplant, according to a retrospective longitudinal study.
The study, “Cause of death analysis and temporal trends in survival after liver transplantation for transthyretin familial amyloid polyneurophathy,” was published in the journal Amyloid.
FAP is a rare, life-threatening disease with a genetic cause — errors (mutations) in the TTR gene, which provides the instructions for production of a protein called transthyretin (TTR).
TTR is mainly produced in the liver; problems in its structure lead to the deposition of amyloid fibrils that accumulate in the peripheral nerves, heart, eyes, gastrointestinal tract and kidneys. Clinical manifestations include cardiac and neurological issues.
Although some medications have been approved to treat the disease, liver transplantation remains the standard therapy. Early transplantation has been shown to improve neuropathy (nerve damage) and survival; however, the 1-year mortality rate after transplantation is 16 percent and 27 percent for 5-year mortality.
Depending on the TTR mutation type, nutritional status, severity of neuropathy and amyloid cardiomyopathy, the prognosis of FAP can vary. However, the causes of death for patients who had a liver transplant and which factors might predict the risk of death remain largely unexplored.
A group of French researchers decided to study the causes of death associated with FAP liver transplants and their related trends.
A total of 215 patients, median age 43 and the majority males (61%), carrying 19 different mutations in the TTR gene were included in the study.
Patients were followed up for a median of 5.9 years, during which time 84 died after liver transplantation. The mean survival after liver transplant was 11.8 years and mean survival after disease onset was 15.9 years.
In the first year after the liver transplant, 13% of the patients died.
Heart problems were the leading cause of death in 38%, and included end-stage heart failure, sudden death and pulmonary embolism.
In 24% of the cases, patients died of infectious disease and 17% from transplant-related complications, including hepatic failure (five patients), hemorrhagic shock (two patients), injury to the small intestine (one patient) and graft versus host disease (one patient).
Graft versus host disease happens when the donor’s immune cells — especially T-cells, which fight infections and cancer — are transplanted with the organ, perceive the recipient’s body as foreign and then react against it.
Transplant complications and infections occurred earlier after liver transplant (5.9 months on average), when compared to cardiovascular causes (55.1 months on average).
The results showed that a late diagnosis of FAP, with a period between first symptoms and surgery of more than two years, was highly associated with infection-related mortality. Risk of cardiovascular-related death was below 50% for the first three years and increased to 75% three years after the liver transplant.
Overall, “in ATTR amyloidosis (FAP), cardiac events were the leading cause of death after liver transplantation,” researchers stated. “Close preoperative evaluation allowed for accurate mid-term prediction of mortality, but the high rate of graft complications and infections blunted the early-term risk prediction.”