To transplant or not to transplant - Lessons learned from 20 years global collaboration in liver transplantation for hereditary transthyretin amyloidosis
Bo-Göran Ericzon1, Henryk E. Wilczek1, Marie Larsson1, Arie J. Stangou3, Priyantha Wijayatunga2, Ole Suhr2;
1Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden; 2Department of Medicine, Umeå university Hospital, Umeå, Sweden; 3NHS Amyloid Treatment Programme, Queen Elizabeth Hospital, Birmingham, United Kingdom
Until recently, liver transplantation (Ltx) was the only available treatment for familial amyloidotic polyneuropathy (FAP), but in the last years several pharmaco-therapeutic approaches have emerged hoping to halt disease progression. In the present study, Ltx as the golden standard of treatment is evaluated in a 20 years perspective by analysis of the FAP world transplant registry (FAPWTR). From April 1990 until December 2010, data from 78 liver transplant centers in 19 countries have been accumulated. Approximately 125 liver transplants are performed yearly worldwide. The Registry holds a total of 1940 patients undergoing 2127 Ltx. 561 patient deaths were reported. Eighty-eight Ltx were performed in combination with a heart or a kidney. Patients undergoing combined Ltx were generally older than those only subjected to Ltx and with a non-Val30Met mutation. The overall 20 year survival after tx, all mutations included, was 55.3%. Expected mortality rate decreased on average by approximately 4% per year between 1 990 and 201 0. In a multivariate analysis modified body mass index (mBMI), early onset of disease, disease duration before Ltx and Val30Met versus non Val30Met were independent significant factors for survival after Ltx. Survival of patients with onset of disease after age 50 was significantly reduced when compared to early onset patients, and most pronounced in the male subgroup. Thus, expected mortality rate in late onset male patients was 137% of that of late onset female patient mortality (p<0.05). Early onset patients (all mutations) had an expected mortality rate of 38% of that of the late onset group (p<0.01). Furthermore, Val30Met patients had an expected mortality rate of 61% of that of non Val30Met patients (p<0.01). With each year of increase in duration of disease before Ltx, the expected mortality increased by 1 1% (p<0.01). Overall, with each unit of increase in mBMI at Ltx, the expected mortality decreased by 0.12% (p<0.01). Twenty-two percent of the death causes were related to cardiovascular disease, thus significantly more common than usually seen in Ltx for end stage liver disease. Conclusion: Long term survival after Ltx for FAP is excellent. A good nutritional status, short duration of disease at the time of Ltx and early onset of disease were significant independent factors for survival. Val30Met patients had significantly better outcome when compared to non-Val30Met patients. The risk of delaying Ltx by testing alternative treatments needs consideration.
The following people have nothing to disclose: Bo-Göran Ericzon, Henryk E. Wilczek, Marie Larsson, Arie J. Stangou, Priyantha Wijayatunga, Ole Suhr