急性肝卟啉症的新治疗选择。
Novel treatment options for acute hepatic porphyrias.
机构信息
Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
出版信息
Curr Opin Gastroenterol. 2021 May 1;37(3):194-199. doi: 10.1097/MOG.0000000000000734.
PURPOSE OF REVIEW
Acute hepatic porphyrias (AHP) are a group of rare diseases that are characterized by episodic acute neurovisceral pain episodes caused by abnormal accumulation of the neurotoxic porphyrin precursor delta-aminolevulinic acid (ALA). Patient with frequent recurrent acute attacks have been difficult to treat and these patients sometimes require liver transplantation. Recent developments in small interfering RNA (siRNA)-based therapy led to the development of an effective prophylactic treatment for patients with frequent recurrent attacks. This review will describe treatment options for AHP and highlight management in light of new treatment option.
RECENT FINDINGS
Givosiran is a novel siRNA-based therapy targeted specifically to hepatocytes to inhibit ALA synthase 1, the first and rate-limiting step in heme biosynthesis. Patients with frequent recurrent attacks treated with givosiran had durable normalization of ALA and significantly reduced numbers of acute attacks and need for hemin treatment. The overall safety profile for givosiran was comparable with placebo and the drug was recently approved by the Food and Drug Administration for treatment of AHP patients.
SUMMARY
Givosiran is an effective treatment for prevention of acute porphyria attacks in AHP patients with frequent recurrent attacks.
目的综述
急性肝卟啉症（AHP）是一组罕见疾病，其特征是由于神经毒性卟啉前体 δ-氨基乙酰丙酸（ALA）的异常积累而导致间歇性急性神经内脏痛发作。经常反复发作急性发作的患者难以治疗，这些患者有时需要进行肝移植。基于小干扰 RNA（siRNA）的治疗的最新进展导致了针对经常反复发作的患者的有效预防性治疗方法的发展。这篇综述将描述 AHP 的治疗选择，并根据新的治疗选择强调管理。
最新发现
吉维森兰是一种新型的 siRNA 治疗药物，专门针对肝细胞，以抑制血红素生物合成的第一个限速酶——ALA 合酶 1。用吉维森兰治疗的经常反复发作的急性发作患者的 ALA 持续正常化，急性发作次数和血红素治疗的需求显著减少。吉维森兰的整体安全性与安慰剂相当，该药物最近已被美国食品和药物管理局批准用于治疗 AHP 患者。
总结
吉维森兰是预防经常反复发作的 AHP 患者急性卟啉症发作的有效治疗方法。
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