Living-donor liver transplantation for homozygous familial hypercholesterolemia from a donor with heterozygous hypercholesterolemia

Abstract

Familial hypercholesterolemia is a rare inherited disease with an incidence of approximately one per million. Severe hypercholesterolemia is observed from the time of birth onwards. It is associated with severe atherosclerosis in childhood, leading to death from myocardial infarction before the age of 20 years. Liver transplantation is the only effective treatment for this disease. We experienced the case of an infant aged 2 years 5 months who had homozygous familial hypercholesterolemia and who received a liver graft from his father, who had familial heterozygous hypercholesterolemia. The pre-operative plasma cholesterol level was > 800 mg/dl. After liver transplantation, the recipient's cholesterol level decreased to 250 mg/dl after we administered the HMC-CoA reductase inhibitor. At present, 6 months after transplantation, the patient is doing well and free from a special diet. We can thus conclude that the combination therapy of liver transplantation from a donor with heterozygous familial hypercholesterolemia on cholesterol-lowering drugs is an effective therapy for a patient with the homozygous type of hypercholesterolemia.

Liver transplantation as a definitive treatment for familial hypercholesterolemia: A series of 36 cases

“…Recently, mutations in the alleles of three other genes were identified as causal in some cases with a severe phenotype resembling HoFH (1,2). Individuals with FH are at an increased risk of developing premature coronary vascular disease (1)(2)(3)(4)(5)(6)(7)(8)(9). Early detection and proper management of the patients will delay and prevent these lethal complications.…”

“…In spite of these treatments, some patients with severe HeFH, and most cases of HoFH, will not reach optimal LDL-C levels. Thus, some other modalities should be performed including LDL aphaeresis, portocaval shunting, ileal bypass surgery, and liver transplantation (1)(2)(3)(4)(5)(6)(7)(8)(9). Besides liver transplantation, other methods are only partially and transiently successful in reducing cholesterol levels in patients with HoFH, so liver transplantation is currently the most effective and definitive means of treatment in patients with HoFH.…”

“…However, in the HoFH, these treatment modalities rarely bring LDL cholesterol to the desired level because homozygous individuals cannot synthesize LDL receptors. Because 70% of LDL receptors are located in the liver, liver transplantation can be a treatment option in medical therapy refractive cases (1)(2)(3)(4)(5)(6)(7)(8)(9).…”

Familial Hypercholesterolemia: a Review of the Natural History, Diagnosis, and Management

“…Liver transplantation was first described in 1983 and has now emerged as the most effective treatment, markedly improving LDL-C levels long term [46, 47]. Surgery provides a liver with functional LDLRs, thereby correcting the molecular defect.…”

Familial homozygous hypercholesterolemia: When to turn to transplant?

“…Prior to 2011, there were six reported cases of preemptive liver transplantation for HoFH performed for their presumed high risk for cardiovascular complications (2)(3)(4)(5). However, in a paradigm shift, in 2011, Maiorana et al reported the case of a seven-yr-old patient with HoFH who underwent preemptive liver transplantation.…”