EFFECT OF ORTHOTOPIC LIVER-TRANSPLANTATION ON THE PROGRESSION OF FAMILIAL AMYLOIDOTIC POLYNEUROPATHY

Background. Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant inherited disease associated with a mutant form of the protei n transthyretin (TTR). It is characterized clinically by the systemic deposition of amyloid fibrils resulting in organ dysfunction and, ulti mately, death. The majority of TTR is produced in the liver, and trans plantation of the liver has been shown to ameliorate this source of mu tant TTR, arresting the progression of this fatal disease. Methods. Th irteen patients with FAP have undergone successful liver transplant su rgery at our center since 1992. The impact of liver transplantation on amyloid-related polyneuropathy, cardiovascular, and gastrointestinal dysfunction is reported in this study. Three patients who died before cardiovascular and neurological follow up are excluded from the analys is. Results. Ten of 13 patients (77%) remain alive an average of 49 mo nths (range, 17-64 months) after transplantation. Three patients suffe red sudden death, with autopsy documentation of amyloid deposits invol ving the conduction system of the heart. Liver transplantation was per formed more quickly, required less blood, and a shorter postoperative hospital stay in these patients, compared with patients with cirrhosis . Neurological and nutritional symptoms improved in the majority of af fected patients. Those patients with echocardiographic evidence of ven tricular wall and valve thickening before transplantation progressed p ostoperatively despite neurologic improvement. Conclusions. Liver tran splantation offers the only cure for the genetic defect causing FAP an d appears to result in subjective and objective improvement in neurolo gical dysfunction. Patients with preexisting cardiovascular abnormalit ies progress despite transplantation; therefore, consideration for com bined heart liver transplantation may be warranted in this subset of p atients.