Mlinaric Matej, Bratanic Nevenka, Dragos Vlasta, Skarlovnik Ajda, Cevc Matija, Battelino Tadej, Groselj Urh
Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Department of Dermatovenereology, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Front Pediatr. 2020 Oct 9;8:567895. doi: 10.3389/fped.2020.567895. eCollection 2020.
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.
纯合子家族性高胆固醇血症（HoFH）是一种罕见的遗传性代谢紊乱疾病，如果治疗不充分，常导致早期心血管死亡。由于标准药物通常无法令人满意地降低低密度脂蛋白胆固醇（LDL-C）水平，低密度脂蛋白去除术是治疗HoFH患者的主要方法，但同时非常繁琐且效果欠佳。肝移植（LT）此前已被证明是一种有前景的替代方法。我们报告了一名HoFH患者肝移植后的14年长期随访情况。该患者4岁时因膝盖、肘部、臀部的黄色瘤数量逐渐增加而转诊至我院，随后证实其低密度脂蛋白受体基因存在纯合突变c.1754T>C（p.Ile585Thr）。尽管随后采用饮食、他汀类药物、胆汁酸螯合剂、普罗布考和低密度脂蛋白去除术进行了强化治疗，但该患者在12岁时出现了瓣膜性主动脉狭窄和主动脉反流。16岁时，患者成功接受了尸体供体原位肝移植。肝移植后9年，我们发现皮肤黄色瘤和动脉粥样硬化斑块完全消退，内皮功能正常。肝移植后14年，他的临床状况保持稳定，但LDL-C水平逐渐升高。此外，我们还对HoFH患者肝移植的文献和指南进行了系统回顾。在17项已确定的指南中，有6项根本没有将肝移植作为一种治疗选择。但大多数指南仍建议将肝移植作为一种特殊的治疗选择或在所有其他治疗选择不足或无法耐受时作为最后手段。大多数观察到的患者在肝移植前都患有某种心血管疾病。在76%的肝移植病例中，肝移植后心血管负担没有进展。根据我们的经验以及其他一些报道的病例，肝移植后LDL-C水平会随着时间缓慢升高。大多数随访数据的期限较短；只有少数病例报告对患者进行了肝移植后10年或更长时间的随访。肝移植是HoFH患者的一种可行治疗选择，可逆转保守治疗无法控制的动脉粥样硬化变化，从而显著改善HoFH患者的预后和生活质量。
