Orthotopic Liver Transplantation for Patients with Familial Amyloid Polyneuropathy: a National Centre Experience

Aims: Familial amyloid polyneuropathies (FAP) are life-threatening, genetic disorders occurring secondary to endoneural deposition of hepatically-derived amyloid. FAP has few available therapeutic options, particularly following the development of cardiac involvement. We aimed to assess whether orthotopic-liver-transplantation (OLT) was capable of halting amyloid-related cardiac disease progression and improving survival. Methods: A retrospective review of case notes, computerised records and prospective departmental databases was performed (May, 1992–October, 2014). Results: Fourteen FAP patients underwent OLT (10M/4F; median age 40 years; median survival 1252 days). Median left ventricular ejection fraction (LVEF) at transplantation was 64% (range 58–68%), ventricular septal thickness (VST) was 1.02 cm (range 0.9–1.6 cm) and New York heart association (NYHA) score was 1 (range 1–2). Twelve patients had a permanent pacemaker and two had an implantable cardioverter/defibrillator. Post-operative complications included one medically-treated hepatic artery thrombosis. There were five deaths: two from sudden cardiac death (day 13/140); one from multi-organ-failure (day 129); one from a cerebrovascular-accident (day 1486); and one from a road-traffic-accident (day 2033). None of the surviving patients have developed further amyloid-related cardiac symptoms. Subsequent domino-liver-transplantation (DLT) was performed in 11 patients for cirrhosis of varying aetiology (5M/6F; median age 58 years; median survival 989 days). Median LVEF at transplantation was 65% (range 60–70%), VST was 1.05 cm (range 0.78–1.4 cm) and NYHA score 1 (range 1–2). Post-operative complications included one radiologically-managed biliary leak. There were four deaths: one from post-operative sepsis (day 47); one from renal failure (day 327); and two from metastatic hepatocellular carcinoma (day 838/2059). None of the surviving patients have developed signs of cardiac or peripheral amyloid to date. Conclusions: These data demonstrate that OLT is effective in halting the progression of cardiac disease in FAP patients, with comparable morbidity/mortality rates to larger OLT cohorts. Further, DLT patients either don't develop, or only slowly develop, clinically-relevant amyloid-related complications. The precise timing of referral for OLT in FAP patients requires further elucidation and multi-centre involvement may be required for the development of larger cohorts.