Liver transplantation for homozygous familial hypercholesterolaemia.

Abstract

Homozygous familial hypercholesterolaemia is a rare inherited condition with an incidence of approximately one in a million. It is associated with severe premature atherosclerosis and early death from cardiovascular complications. The results ofliver transplantation reported to date have suggested only partially effective reduction of the hypercholesterolaemia.Three boys with familial hypercholesterolaemia, aged 10-0 to 151 years, received liver grafts at Addenbrooke's Hospital. Their untreated fasting lipid concentrations were grossly raised. All three had angiographic evidence of coronary atheroma and two had exertional angina. One child had such severe atheroma that coronary artery bypass surgery was considered necessary before liver transplantation. All three had straightforward operative and postoperative courses and their lipid concentrations returned rapidly to normal. One boy developed chronic rejection requiring retransplantation. Currently all three boys are well, on normal diets, and with normal liver function.It is concluded that (1) liver transplantation offers highly effective treatment for this lethal condition, (2) timing the operation is difficult but it should be undertaken before coronary artery disease has progressed too far (when combined liver and heart transplantation may be the only possibility), and (3) We describe three children in whom liver transplantation fully corrected the lipid abnormality.Case reports PATIENT 1 This English boy developed xanthomata at 11 months of age and was found to have the typical lipid profile of homozygous familial hypercholesterolaemia. Initially he was treated with a low fat diet only but from the age of 9 years cholestyramine and nicotinic acid were added. Coronary angiography was normal at that time but when repeated four years later showed a 30% stenosis of the proximal left descending coronary artery. He remained asymptomatic and no ischaemic changes were seen on an electrocardiogram (ECG). His treatment was intensified and for two years he had weekly plasma exchanges. Although this produced a satisfactory fall in lipid concentrations he found the treatment extremely burdensome and it was complicated by multiple central line infections. He was therefore referred for consideration of liver transplantation.He received a whole liver graft in October 1990 and had an uncomplicated perioperative course. The donor was cytomegalovirus positive and the patient developed cytomegalovirus hepatitis which resolved fully after a course of ganciclovir. His lipid profile and liver function returned to normal two weeks after transplantation (table and figure). He was well and had a normal lipid profile and normal liver function 3-8 years after the operation. PATIENT 2 This Asian son of a first cousin marriage developed xanthomata at the age of 6 years and was found to have familial hypercholesterolaemia. In spite of treatment with a low fat diet, cholestyramine and simvastatin, his cholesterol remained greatly raised. Coronary angiography at the age of ...

Homozygous Familial Hypercholesterolemia with Generalized Arterial Disease

“…An average plasma concentration of LDL cholesterol lower than 5.4 mmol/l can be achieved by treating patients once a week [9] . Along with the improvement of the plasma atherogenic profile, regression of cutaneous xanthomas and prevention of progression of coronary heart disease have been shown to avert early death [2,10] . A combination of apheresis and statins was found to improve LDL reduction in subjects who had absent or minimal receptor activity [2] .…”

Successful living-related liver transplantation for familial hypercholesterolemia in the Middle East

“…In those patients evaluated prior to the onset of significant atherosclerosis, liver transplantation cures the underlying disease because 50-75% of the entire body's LDL receptors exist within the liver. As a result, liver transplantation provides the patient with enough LDL receptors to prevent the onset of clinical disease [16,17,18,191. As in our case, mild hypercholesterolemia may persist after liver transplantation but can be managed with statins.…”

Combined heart and liver transplantation in an adult with familial heterozygous hypercholesterolemia and severe ischemic cardiomyopathy

“…2 Our patient, an adult with heterozygous FH underwent dual-organ heart-liver transplantation and had an excellent outcome. In conclusion, CHLT is a viable option for the management of this challenging group of patients.…”

“…1 Liver transplantation restores defective LDL receptors and has been used for long-term treatment in homozygous FH. 2 We report a 34-year-old man who underwent combined heart-liver transplantation (CHLT) for end-stage ischemic heart failure and heterozygous FH. The patient presented with heart failure and was found to have severe left ventricular dysfunction.…”