Liver transplantation in a subject with familial hypercholesterolemia carrying the homozygous p.W577R LDL-receptor gene mutation.

Schmidt HH, Tietge UJ, Buettner J, Barg-Hock H, Offner G, Schweitzer S, Dedoussis GV, Rodeck B, Kallfelz HC, Schlitt HJ, Oldhafer K, Klempnauer J.
Transplantationshepatologie, Universitätsklinikum Münster, Münster, Germany. This e-mail address is being protected from spambots. You need JavaScript enabled to view it

Mutations within the low density lipoprotein (LDL)-receptor gene result in familial hypercholesterolemia, an autosomal dominant inherited disease. Clinical homozygous affected subjects die of premature coronary artery disease as early as in early childhood. We identified a girl at the age of five yr with clinical homozygous familial hypercholesterolemia presenting with achilles tendon xanthomas and arcus lipoides. Her total cholesterol reached up to 1050 mg/dL. Molecular characterization of the LDL-receptor gene revealed a homozygous p.W577R mutation. Despite intensive treatment interventions with the combination of diet, statins, colestipol, and LDL-apheresis, the patient developed symptomatic coronary artery disease at the age of 16 yr. Subsequently, orthotopic liver transplantation was performed to cure the defective LDL-receptor gene. Clinical follow-up for almost nine yr post-transplantation revealed excellent liver function, normal liver enzymes, normal LDL-cholesterol, and regression of both tendon xanthomas and symptomatic coronary artery disease. In conclusion, liver transplantation can effectively reduce LDL-cholesterol in a familial hypercholesterolemia recipient with subsequent regression of xanthomas and atherosclerosis. Timing is extremely important in these exceptional cases to exclude the demand for heart transplantation due to severe coronary artery disease. In addition, the identification of the LDL-receptor as etiology of clinical homozygous hypercholesterolemia is a prerequisite once liver transplantation is considered as therapeutic option.

Domnul Schmidt H care a scris acest articol ne ajuta cu testele genetice si cu sfaturi medicale. El ne face gratuit aceste teste şi în regim de urgenţă (cu rezultatul în două săptămâni), în condiţiile în care la Bucuresti costul acestora ajunge la 5.400 RON (cu rezultatul în 3-4 luni).

Role of orthotopic liver transplant in the treatment of homozygous familial hypercholesterolemia.

Castilla Cabezas JA, López-Cillero P, Jiménez J, Fraga E, Arizón JM, Briceño J, Solórzano G, De la Mata M, Pera C.
Liver Unit Transplantation, Hospital Universitario Reina Sofía, Córdoba, Spain. This e-mail address is being protected from spambots. You need JavaScript enabled to view it

Homozygous familial hypercholesterolemia is an inherited metabolic disease that leads to decreased catabolism of low-density lipoprotein cholesterol. As a result coronary artery disease ensues by the first or second decade. Because most low-density lipoprotein receptors (50-75%) are located in the liver, liver transplantation has been introduced as a therapeutic option in this disorder. AIMS: To report our experience in the treatment of homozygous familial hypercholesterolemia with ortothopic liver transplantation. We evaluated metabolic results and patient survival. METHOD: We treated two affected siblings. One of them received a sequenced heart-liver transplantation because of cardiac failure due to severe coronary disease. RESULTS: The operative and postoperative course was favourable in both patients, with a decrease in cholesterol levels to normal values. Four years later both were alive and both had normal liver and heart functions. Neither patient needed cholesterol-lowering drugs, and the disease had not progressed. CONCLUSIONS: As shown by our results and those reported by others, liver transplantation is the treatment of choice for homozygous familial hypercholesterolemia until gene therapy becomes a viable option. Transplantation should be done before of cardiovascular complications develop.

Domnul Castilla Cabezas ne-a raspuns promt si ne-a dat sfaturi medicale.

Liver transplant combined with heart transplant in severe heterozygous hypercholesterolemia: report of the first case and review of the literature.

Alkofer BJ, Chiche L, Khayat A, Deshayes JP, Lepage A, Saloux E, Reznik Y.
CHU Caen, Transplantation and Liver Surgery, CHU cote de nacre, Caen 14000, France. This e-mail address is being protected from spambots. You need JavaScript enabled to view it

Familial hypercholesterolemia (FH) is a dominant inherited disease of low-density lipoprotein (LDL) metabolism caused by mutations of LDL receptors mainly located in the liver. This metabolic disorder is responsible for severe cardiovascular disease, from coronary lesions to chronic heart failure (CHF). Liver transplantation in homozygous FH provides the missing functional LDL receptors and thus partially restores LDL receptor activity to more than 50% of normal. Combined heart and liver transplantation was successfully performed in a homozygous FH patient with end-stage heart failure. Herein we report our experience with a heterozygous male patient with terminal CHF, and review data from the literature on short- and long-term results of such procedures.

Un site interesant cu statistici privind transplantul de ficat în Europa:

http://www.eltr.org/publi/results.php3?id_rubrique=44

Current management of severe homozygous hypercholesterolaemias

Long-term Outcome after Living Donor Liver Transplantation for Two Cases of Homozygous Familial Hypercholesterolemia from Heterozygous Donor

3-month and 12-month mortality after first liver transplant in adults in Europe: predictive models for outcome