Clinical symptomatic de novo systemic transthyretin amyloidosis 9 years after domino liver transplantation

Abstract

Four years ago, Stangou et al.1 reported a patient who developed clinical symptoms of amyloidosis 8 years after domino liver transplantation (DLT). In order to alleviate the graft shortage, livers from patients with familial amyloidotic polyneuropathy (FAP) are used as domino grafts for other patients under the assumption that several decades will pass before clinical symptoms due to amyloid accumulation emerge. We now report on another case, the third reported case in the literature, of de novo systemic amyloidosis in a 75-year-old woman 9 years after DLT. The patient underwent DLT at 65 years of age for hepatocellular carcinoma exceeding the Milan criteria in hepatitis C cirrhosis. Transarterial chemoembolization was performed before liver transplantation. During treatment, progressive cachexia and increasing B symptoms occurred. Therefore, DLT was finally considered in this patient. The posttransplant course was uneventful. In 2006, the patient described progressive dysesthesia in the lower extremities. Immunosuppression was switched from a calcineurin inhibitor to a mammalian target of rapamycin inhibitor. Other reasons for neuropathy were excluded. A rectal biopsy specimen at this time was free of amyloid deposition. In 2007, neurological symptoms further deteriorated: burning pain and progressive sensory loss in the lower limbs occurred. In March 2008, amyloid deposition was detected in the gastrointestinal wall, reflecting de novo FAP in this patient. A literature review revealed 2 case reports of symptomatic patients: in the first patient, dysesthesia of the lower limb 8 years after DLT was described,1 and in the second patient, decreased temperature sensation and pain in the toes and fingertips 7 years after DLT were reported.2 Interestingly, in our patient and in both previously reported patients, neuropathic symptoms occurred after comparable intervals after DLT (7 and 8 versus 9 years), and the indication for DLT was hepatocellular carcinoma with underlying hepatitis C cirrhosis in the first described patient1 and our patient. All the patients had received an FAP graft with a transthyretin mutation; the former 2 received grafts with a Val30Met mutation, and our patient received a graft with a Gly47Glu mutation. In individuals with both inherited mutations, neurological symptoms usually occur within the age range of 20 to 35 years.3 After DLT, the onset of symptoms was thus significantly earlier than the onset in inherited FAP patients. Despite the risk of emerging amyloidosis in recipients, the graft shortage and increasing death rates on the waiting lists prompt alternative approaches to providing grafts. DLT is a feasible technique and may, therefore, be justified in selected patients. Nevertheless, our data reinforce the need for additional caution and meticulous follow-up programs. Ana Paula Barreiros*, Christian Geber , Frank Birklein , Peter R. Galle*, Gerd Otto , * Department of Internal Medicine I, Johannes Gutenberg University, Mainz, Germany, Department of Neurology, Johannes Gutenberg University, Mainz, Germany, Department of Transplantation Surgery, Johannes Gutenberg University, Mainz, Germany.