Progression of transthyretin (TTR) amyloidosis in donors and recipients after domino liver transplantation-a prospective single-center cohort study

Abstract

Liver transplantation (LT) is the first-line therapy in patients with transthyretin (TTR) amyloidosis and progressive familial amyloid polyneuropathy (FAP). Explanted organs from these patients can be used for domino liver transplantation (DLT). After DLT, de novo amyloidosis may develop in domino recipients (DR). Data were collected prospectively in a transplant database. Electroneurography by nerve conduction velocity (NCV), quantitative sensory testing, heart rate variability (HRV), sympathetic skin response, orthostatic reaction (tilt table test), transthoracic echocardiography, cardiac MRI and organ biopsy results were evaluated. The cohort included 24 FAP- (11 Val30Met, 13 nonVal30Met) and 23 DR-patients. DR symptoms referred to post-DLT only, while those of FAP patients were both pre- and post-transplantation. Symptoms of TTR-amyloidosis in Val30Met and Non-Val30Met patients pre- and post-LT were similarly distributed. Biopsy-proven de novo amyloidosis occurred in 4/23 DR after a mean observation of 10 years. Analysis for manifestations of amyloidosis only included patients with available 5-year follow-up data (n = 13 FAP, n = 12 DR). Compared to Val30Met FAP patients pre-LT, Val30Met DR patients had better NCV (P = 0.04) and HRV (P = 0.015). In the Non-Val30Met group no differences were found between DR and FAP patients pre-LT. TTR-amyloidosis symptoms showed no differences in FAP patients pre- and 5 years post-LT, irrespective of Val30Met status. In DR patients, de novo amyloidosis occurred earlier than expected. Therefore, recipients for DLT need to be carefully selected and followed.

Solid Organ Transplantation in Amyloidosis

“…Other case reports followed. FAP presents at approximately 7–9 years following domino LT, which is earlier than expected [81, 82] by the natural history of the disease. Factors that interfere with the natural history of the disease may play a role in the development of de novo ATTR.…”

The concept of “domino” in liver and hepatocyte transplantation

“… 40 , 41 Several recent studies have found that the number of patients with acquired transthyretin amyloidosis following domino LT with FAP liver grafts is increasing, and the interval from transplantation to the development of amyloidosis is much shorter than expectations. 18 , 42 To minimize the potential risk of complications related to metabolic deficiencies in recipients, the transplant team should have sufficient knowledge on the characteristics of such diseases, and careful selection is required for domino graft recipients. Furthermore, potential candidates for domino LT should be fully informed of the potential risks of disease transmission related to the domino liver grafts.…”

Domino-liver transplantation: toward a safer and simpler technique in both donor and recipient

“…DLT is normally only used in elderly and/or cancer patients [6,7]. The non-use of these potentially excellent liver allografts has four reasons: (a) ethical concerns about putting the domino-donor at risk of a more complex surgical procedure and the domino-recipient for a possible disease transmission (reported in 3.3-21% of domino-recipients); (b) fear of technical complications related to a more difficult arterial inflow and venous outflow reconstruction of the domino-allograft; (c) increased logistics linked to the organization of two simultaneous, LT procedures, and finally (d) the (intra-operative) discovery of advanced liver fibrosis ('cardiac liver') caused by the underlying amyloidotic cardiopathy [8][9][10][11][12][13][14].…”