Liver transplantation in transthyretin familial amyloid polyneuropathy: First report from Argentina

Abstract

This is the first report from Argentina of liver transplantation in patients with transthyretin related familial amyloidotic polyneuropathy. The aims of the study were to analyze the clinical characteristics of this new focus and evaluate the postoperative complications and long term follow up. Five of ten patients evaluated underwent liver transplantation. During the waiting period the polyneuropathy disability score in each patient progressed one or two stages. Pretransplant modified body mass index was 723. The procedure was done with full size grafts in four cases and a split right graft in one. All patients presented postoperative complications related to disease: severe edema of the legs, recurrent choledochal lithiasis, postoperative hernia, necrotizing fasciitis and ischemic rectosigmoidal perforation. Assessment of three patients after 20 months of transplantation showed improvement in somatic and mental symptoms. No improvement was noted in cardiac denervation and gastric stasis. Liver transplantation is a rational therapeutic option for transthyretin familial amyloidotic polyneuropathy in Argentina and should be indicated in earlier stages of the symptomatic disease to reduce the postoperative morbidity and mortality. Family studies and follow up of asymptomatic carriers will define the epidemiological behavior in this country and facilitate early therapeutic intervention.

Loss of functional albumin triggers acceleration of transthyretin amyloid fibril formation in familial amyloidotic polyneuropathy

“…7,8,32,33 Despite the need for such alternative therapeutic strategies, the pathogenesis of FAP, especially the precise Figure 5 Transthyretin (TTR) deposition in analbuminemic amyloidogenic transthyretin (ATTR) V30M Tg rats. (a) Equal amounts of serum protein from rats were analyzed by SDS-PAGE for albumin (upper panel) and by western blotting for human ATTR V30M (lower panel).…”

A different amyloid formation mechanism: de novo oculoleptomeningeal amyloid deposits after liver transplantation

“…By the end of 2000, more than 500 FAP patients had undergone the surgery, with approximately 80% of the patients surviving (2). Liver transplantation is now considered a promising therapy for prevention of deterioration of neurologic complications of FAP patients (1,(3)(4)(5)(6)(7). After transplantation, variant TTR levels in serum have decreased to below 1% of those before transplantation, and clinical findings have improved, or at least the patients' conditions did not deteriorate (8).…”

“…FAP ATTR Val30Met is characterized by progressive sensorimotor peripheral neuropathy in addition to symptoms in the gastrointestinal tract, heart, kidney, and autonomic nervous system (14,15). Liver transplantation has been reported to halt the progression of these clinical manifestations (1,(3)(4)(5)(6)(7). However, changes in manifestations in the eye and central nervous system (CNS) have not been carefully evaluated, and no precise or long-term follow-up documentation is available.…”

Gene Therapy by Liver Transplantation and Single Stranded Oligonucleotides (SSOs) in Familial Amyloidotic Polyneuropathy (FAP)

“…Recently, liver transplantation has become a wellestablished treatment for halting the progression of FAPrelated clinical symptoms, because the main source of serum variant TTR is shut out [Holmgren et al 1993;Ericzon et al 2000;Skinner et al 1994;Takei et al 1999;Ando et al 1995a;Suhr et al 1996;Lendoire et al 1999]. However, there are several problems with this therapy: (1) Medical cares before and after the surgery and the surgery itself are extremely expensive.…”