LIVER TRANSPLANTATION FOR TRANSTHYRETIN SYSTEMIC AMYLOIDOSIS DISORDERS: AN UPDATED REVIEW FROM THE FAMILIAL AMYLOIDOTIC POLYNEUROPATHY WORLD TRANSPLANT REGISTER (FAPWTR)

OUTCOMES OF LIVER TRANSPLANTATION I

H.E. Wilczek¹, M. Larsson¹, A.J. Stangou², O. Suhr³, B. Ericzon^1
1Dept Of Transplantation Surgery, Karolinska Institute, Stockholm/SWEDEN, ²Institute Of Liver Studies And Amyloidosis Treatment Centre, King's College Hospital, London/UNITED KINGDOM, ³Dept Of Medicine, Umeå University Hospital, Umeå/SWEDEN

Body: Introduction/Methods: Several hereditary amyloidosis disorders can be treated with liver transplantation (Ltx). The FAPWTR exists since 1993 and gets data on these patients from centres all over the world. Results: By Dec 2009, a total of 70 centres from 18 different countries reported patients to the FAPWTR. A total of 1536 patients underwent 1660 liver transplantations. 37 patients received a combined liver/kidney graft and 25 patients a combined liver- and heart transplantation. 81 LTx:s were done with grafts from living related donors. Patients with more than 45 different variants of TTR mutations have been transplanted, the most common being Val30Met (83%) followed by Ser77Tyr, Thr60Ala and Tyr114Cys (1-2% each, respectively). 1274 of the FAP patients had the Val30Met TTR mutation, 196 patients had a nonVal30Met variant, 11 were non-TTR variants and in 55 patients information was missing or unknown. Most transplantations have been done in Portugal (n=650), France (n=207), Sweden (n=130), USA (n=79), UK (n=78), Brazil (n=71) and Spain (n=72).

	Val30Met	nonVal30Met	p-value
Males/females (%)	56/44	65/35	<0.05
Age at transplantation (years)	39±10	50±11	<0.001
Duration of symptoms (years)	4.0±1.7	4.1±3.5	n.s.
mBMI at transplantation	850±213	889±189	<0.05
Type of Transplantation
Liver	98.0%	87.6%
Liver+kidney	1.8%	0.5%
Liver+heart	0	9.3%
Liver+heart+kidney	0	0.5%
Liver after heart	0.2	2.1%
Initial symptom
Sensory loss	70.2%	36.4%	<0.001
Gastrointestinal (g-i) dysfunction	10.2%	20.9%	<0.001
Pain	9.3%	4.7%	n.s.
Cardiovascular manifestations	0.9%	7.8%	<0.001
Extraneurological manifestation	0.7%	8.5%	<0.001

NonVal30Met patients have more g-i, cardiovascular and extraneurological manifestations than Val30Met patients. Approximately 80-90 % of the LTx ValMet30 patients report stable or improved clinical symptoms, the corresponding numbers among nonVal30Met patients is 60-65%. With regard to cardiovascular status, 83% of the Val30Met patients report stable or improved status versus 59% in nonVal30Met patients (p<0.001). Analyzing cardiovascular improvement only, the number is 6% in both groups. Interestingly, two asymptomatic patients are also reported to have been transplanted. In the Val30Met group 278 patients (22%) died compared to 86 patients (44%) in the non-Val30Met group (p<0.0001). The overall 5- and 10-year patient survival in Val30Met patients was highly significantly better than in nonVal30Met mutations (5 year 82.2 % and 59.7 %, respectively, p<0.0001; 10 year 75.4% and 46.0, respectively, p<0.0001). However, the survival difference vanished when re-analysing the survival in patients transplanted in the last 5 years (89.6% and 82.3%, respectively, ns). Overall, cardiovascular related death and septicemia were the main causes of death (26% and 24%, respectively). Certain TTR mutations appear to entail a greater risk of cardiac related deaths. Conclusion: LTx in patients with TTR amyloidosis disorders saves lives and the FAPWTR data confirm the advantage of early transplantation. Val30Met differs clinically from other TTR mutations. NonVal30Met patients appear more often to require combined liver-heart transplantation. The previously observed highly significant post-transplantation survival difference between Val30Met and non-Val30Met mutations disappeared when analyzing the last 5 years. This may reflect improved pre- and post-transplantation patient handling combined with better selection criteria for liver transplantation.

Disclosure: All authors have declared no conflicts of interest.