Department of Medicine, UCLA Health, Los Angeles, CA, USA.
Clinical Fellow in Gastroenterology, Department of Gastroenterology, UCLA Health, Los Angeles, CA, USA.
Expert Opin Biol Ther. 2023 Jul-Dec;23(12):1245-1253. doi: 10.1080/14712598.2023.2273260. Epub 2023 Dec 28.
Hepatitis delta virus (HDV) causes acute and chronic liver disease that requires the co-infection of the Hepatitis B virus and can lead to significant morbidity and mortality. Bulevirtide is a recently introduced entry inhibitor drug that acts on the sodium taurocholate cotransporting peptide, thereby preventing viral entry to target cells in chronic HDV infection. The mainstay of chronic HDV therapy prior to bulevirtide was interferon alpha, which has an undesirable side effect profile.
We review bulevirtide data from recent clinical trials in Europe and the United States. Challenges to development and implementation of bulevirtide are discussed. Additionally, we review ongoing trials of emerging drugs for HDV, such as pegylated interferon lambda and lonafarnib.
Bulevirtide represents a major shift in treatment for chronic HDV, for which there is significant unmet need. Trials that compared bulevirtide in combination with interferon alpha vs interferon alpha monotherapy demonstrated significant increase in virologic response. Overall, treatment with different doses of bulevirtide were comparable. Bulevirtide was generally well tolerated, and no serious adverse events occurred. Understanding the true prevalence of HDV, as well as continued studies of emerging drugs will prove valuable to the larger goal of eradication of Hepatitis D.
乙型肝炎 delta 病毒(HDV)可引起急性和慢性肝脏疾病,需要乙型肝炎病毒的共同感染,可能导致显著的发病率和死亡率。Bulevirtide 是一种新引入的进入抑制剂药物,作用于牛磺胆酸钠共转运多肽,从而防止慢性 HDV 感染中的病毒进入靶细胞。在 bulevirtide 之前,慢性 HDV 治疗的主要方法是干扰素α,但其具有不理想的副作用谱。
我们回顾了欧洲和美国最近的临床试验中有关 bulevirtide 的数据。讨论了 bulevirtide 开发和实施所面临的挑战。此外,我们还回顾了正在进行的针对 HDV 的新兴药物试验,如聚乙二醇干扰素λ和 lonafarnib。
Bulevirtide 代表了慢性 HDV 治疗的重大转变,该病存在巨大的未满足需求。将 bulevirtide 联合干扰素α与干扰素α单药治疗进行比较的试验显示,病毒学应答显著增加。总体而言,不同剂量的 bulevirtide 治疗效果相当。Bulevirtide 通常耐受性良好,没有发生严重不良事件。了解 HDV 的真实流行情况,以及对新兴药物的持续研究,将对消灭乙型肝炎 D 的更大目标具有重要价值。