Pharmacotherapy Before or After Liver Transplantation in Familial Amyloidotic Polyneuropathy (FAP) and Domino recipients – Early Report from the Familial Amyloidotic World Transplant Registry (FAPWTR) and the Domino Liver Transplant Registry (DLTR)
Henryk Wilczek1, Marie Tranäng1, Bo-Göran Ericzon1.
1Division of Transplantation Surgery, Karolinska Institutet, CLINTEC, Karolinska University Hospital, Huddinge, Stockholm, Sweden
on behalf of the members of the FAPWTR and the DLTR.
Background: Liver transplantation (LTx) as treatment for hereditary transthyretin amyloidosis (hATTR) has been performed since 1990, when the first hATTR patient with the TTR Val30Met mutation was done in Sweden with overall good outcome. However, with time publications appeared disclosing not only an unhalted disease progression but also progress of cardiomyopathy in a number of patients with regard to some non-Val30Met mutations and ensuing notably for elderly male hATTR Val30Met patients. With the introduction of medical therapy, LTx as treatment for hATTR patients has been significantly reduced. The use of hATTR livers for domino liver transplantation (DLT) is since many years an established way to expand the liver donor pool. However, the procedure carries the risk of transmitting the novo amyloidosis to the recipient with the grafted liver, and several reports indicate the risk to be very real. Using TTR stabilizers is maybe of value for these patients. As all new treatment modalities must be balanced against previous treatments, the long-term survival after TTR stabilizer treatment is yet to be settled. Furthermore, the variable response to TTR stabilizer treatment poses a problem, because delayed transplantation for a patient in whom an acceptable outcome is to be expected will significantly decrease survival.
Methods: All patients reported to the FAPWTR and DLTR are included in the analysis.
Results: By Oct 2017, the FAPWTR had data on 2185 hATTR liver transplant recipients and the DLTR contained data on 1186 transplantations with a FAP liver, reported from 21 countries. The first patient given TTR stabilizers before LTx was registered in 2012, and since then 28 patients (20% of LTx patients reported to the FAPWTR since 2012) were reported to be on stabilizer medication before LTx. Duration of pretranplantation medical therapy was 13±10 month (range 3-44).
Overall, the frequency of retransplantation (retx) in the DLT recipients was 6.7%. The main reason for retx was arterial thrombosis (27.8%). 10 (12.7%) of the retx were because of de novo amyloidosis. 16 (1.4%) of the patients had been given TTR stabilizers post-DLT. In these patients, the treatment was started 5-13 years after DLT, mean 10.5 years (median 11.1 years).
Conclusion: These early Registry data show that some hATTR patients will still need LTX despite being given TTR stabilizer medication. To date, only scarce literature has been published on the use of TTR stabilizers relative to LTx. Medical therapy as adjuvant treatment to LTx has not yet been evaluated long enough to establish its definite role relative to LTx. Adjuvant medical therapy and LTx may be relevant particularly for patients displaying worsening after LTx or in DLT recipients.
