Case Report: Liver Transplantation in Homozygous Familial Hypercholesterolemia (HoFH)—Long-Term Follow-Up of a Patient and Literature Review

Abstract

Homozygous familial hypercholesterolemia (HoFH) is a rare inherited metabolic disorder, frequently leading to an early cardiovascular death if not adequately treated. Since standard medications usually fail to reduce LDL-cholesterol (LDL-C) levels satisfactorily, LDL-apheresis is a mainstay of managing HoFH patients but, at the same time, very burdensome and suboptimally effective. Liver transplantation (LT) has been previously shown to be a promising alternative. We report on a 14 year-long follow-up after LT in a HoFH patient. At the age of 4, the patient was referred to our institution because of the gradually increasing number of xanthomas on the knees, elbows, buttocks, and later the homozygous mutation c.1754T>C (p.Ile585Thr) on the LDL-receptor gene was confirmed. Despite subsequent intensive treatment with the combination of diet, statins, bile acid sequestrant, probucol, and LDL-apheresis, the patient developed valvular aortic stenosis and aortic regurgitation by 12 years. At 16 years, the patient successfully underwent deceased-donor orthotopic LT. Nine years post-LT, we found total regression of the cutaneous xanthomas and atherosclerotic plaques and with normal endothelial function. Fourteen years post-LT, his clinical condition remained stable, but LDL-C levels have progressively risen. In addition, a systematic review of the literature and guidelines on the LT for HoFH patients was performed. Six of the 17 identified guidelines did not take LT as a treatment option in consideration at all. But still the majority of guidelines suggest LT as an exceptional therapeutic option or as the last resort option when all the other treatment options are inadequate or not tolerated. Most of the observed patients had some kind of cardiovascular disease before the LT. In 76% of LT, the cardiovascular burden did not progress after LT. According to our experience and in several other reported cases, the LDL-C levels are slowly increasing over time post LT. Most of the follow-up data were short termed; only a few case reports have followed patients for 10 or more years after LT. LT is a feasible therapeutic option for HoFH patients, reversing atherosclerotic changes uncontrollable by conservative therapy, thus importantly improving the HoFH patient's prognosis and quality of life.

Is Liver Transplant Curative in Homozygous Familial Hypercholesterolemia? A Review of Nine Global Cases

“…This occurred in spite of the introduction of atorvastatin 3–4 weeks after transplantation [ 23 ]. A recent case report from Slovenia described a 16-year-old patient with HoFH who underwent a deceased donor liver transplant with LDL-C levels up to 449 mg/dL (11.6 mmol/L) on LA and atorvastatin [ 25 ]. The response to liver transplant (LDL-C reduced to 201 mg/dL) (5.2 mmol/L) prompted the medical team to stop the statin and LA; however, the patient had to undergo a course of steroids for an episode of acute rejection.…”

“…LDL-C levels never reached recommended targets for patients with HoFH and remained at more than double that level (approx. 160–200 mg/dL; 4.1–5.2 mmol/L), with the LDL-C levels continuously increasing at the time of the report (14.5 months post-transplant) [ 25 ]. In the case series presented here, only two of the surviving patients were able to achieve EAS guideline targets for LDL-C in patients with HoFH, and only one of these did so without additional support from standard LLTs.…”

Novel Gene-Correction-Based Therapeutic Modalities for Monogenic Liver Disorders

“…Recent data have shown that the incidence of homozygotic FH is 1 in 1,000,000, while HeFH is 2000 times more frequent (1:500) [ 49 ]. LT is considered to be a gold standard treatment, but it is invasive and may cause other complications [ 50 ]. LDL apheresis is another therapeutic option, limited due to high costs and difficulty to apply [ 51 ].…”

Familial homozygous hypercholesterolemia in children: early diagnosis and treatment

“…ECG signs of subendocardial ischemia (ST segment depression at 7-8 mm) during a dosed exercise test in a child with homozygous hypercholesterolemia (own observations). В ПОМОЩЬ ПРАКТИЧЕСКОМУ ВРАЧУ случаев удается остановить дальнейшее развитие атеросклеротического поражения сердечно-сосудистой системы, в 24,4% отмечается прогрессирование атеросклеротического процесса и только в 12,3% происходит регресс атеросклероза (ксантом и атеросклеротических бляшек в сосудах) [37]. Ограничения трансплантации печени: необходимость постоянной иммунносупрессивной терапии и возможные послеоперационные осложнения [36,37].…”

“…В ПОМОЩЬ ПРАКТИЧЕСКОМУ ВРАЧУ случаев удается остановить дальнейшее развитие атеросклеротического поражения сердечно-сосудистой системы, в 24,4% отмечается прогрессирование атеросклеротического процесса и только в 12,3% происходит регресс атеросклероза (ксантом и атеросклеротических бляшек в сосудах) [37]. Ограничения трансплантации печени: необходимость постоянной иммунносупрессивной терапии и возможные послеоперационные осложнения [36,37]. В случае выраженного атеросклеротического процесса в сердце (коронарный атеросклероз, поражения аортального клапана) осуществляется комбинированная трансплантация сердца и печени [34,35].…”