Bulevirtide治疗HDV相关代偿性肝硬化的安全性和有效性

StephenW

Safety and Effectiveness of Bulevirtide for HDV-Related Compensated Cirrhosis
Virginia A. Schad, PharmD, RPh


Bulevirtide, an entry inhibitor, combined with tenofovir disoproxil fumarate (TDF), demonstrated excellent safety and effectiveness for the treatment of hepatitis D virus (HDV)-related compensated cirrhosis in a study published in the Journal of Hepatology.

Chronic HDV-induced hepatitis typically has a more rapid progression to cirrhosis and provokes more complications than hepatitis B virus (HBV) infection. Although there are few therapeutic options for HDV, short-term administration of bulevirtide has been shown to be safe and effective in phase 2 studies in HBV/HDV co-infected patients. However, its effectiveness and safety during long-term and high-dose treatment in compensated cirrhotics is unknown. Therefore, researchers observed 3 European patients with HDV-related compensated cirrhosis who were treated with bulevirtide 10 mg/day for 48 weeks. They found that HDV RNA levels progressively declined from 4.4 and 5.6 logs IU/mL to undetectability in 2 patients, and from 6.8 log cp/mL to 500 cp/mL in the third patient. The alanine aminotransferase level normalized at 20, 12, and 28 weeks in the 3 patients, respectively. The researchers also noted a significant improvement in portal hypertension features, liver function tests, and serum alpha-fetoprotein levels in 2 patients. Immunoglobulin G and other immunoglobulins rapidly normalized in a patient with autoimmune hepatitis. In addition, no significant changes in hepatitis B surface antigen levels and circulating HDV/HBV-specific T cells were demonstrated, and HBV DNA and RNA levels remained undetectable throughout the study. Bulevirtide was found to be well tolerated.


The authors concluded that, “[t]he excellent virological and biochemical responses induced and maintained by long-term administration of [bulevirtide] monotherapy coupled with a favorable safety profile may represent an interesting therapeutic approach for a difficult to treat and aggressive disease such as hepatitis Delta.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Loglio A, Ferenci P, Colonia Uceda Renteria S, et al. Excellent safety and effectiveness of high dose myrcludex-b monotherapy administered for 48 weeks in hdv related compensated cirrhosis: a case report of three patients [published online July 11, 2019]. J Hepatol. doi:10.1016/j.jhep.2019.07.003

StephenW

Bulevirtide治疗HDV相关代偿性肝硬化的安全性和有效性
Virginia A. Schad，PharmD，RPh


Bulevirtide是一种入门抑制剂，与替诺福韦地索普西富马酸盐（TDF）联合使用，在一项发表在“肝病学杂志”上的研究中证明了治疗丁型肝炎病毒（HDV）相关代偿性肝硬化的安全性和有效性。

慢性HDV诱导的肝炎通常比乙型肝炎病毒（HBV）感染更迅速地进展为肝硬化并引起更多的并发症。尽管HDV的治疗选择很少，但在HBV / HDV合并感染患者的2期研究中，短期使用bulevirtide已被证明是安全有效的。然而，其在补偿性肝硬化的长期和高剂量治疗期间的有效性和安全性是未知的。因此，研究人员观察了3名患有HDV相关代偿性肝硬化的欧洲患者，他们使用bulevirtide 10 mg /天治疗48周。他们发现2名患者的HDV RNA水平从4.4和5.6 log IU / mL逐渐下降至不可检测性，第3名患者的HDV RNA水平从6.8 log cp / mL降至500 cp / mL。在3名患者中，丙氨酸氨基转移酶水平分别在20,12和28周归一化。研究人员还指出，2例患者的门静脉高压症特征，肝功能检查和血清甲胎蛋白水平有显着改善。免疫球蛋白G和其他免疫球蛋白在患有自身免疫性肝炎的患者中迅速正常化。此外，未证实乙型肝炎表面抗原水平和循环HDV / HBV特异性T细胞的显着变化，并且在整个研究中HBV DNA和RNA水平仍未检测到。 Bulevirtide被发现具有良好的耐受性。


作者得出结论认为，“通过长期服用[bulevirtide]单药治疗诱导和维持良好的病毒学和生化反应，加上有利的安全性，可能代表了一种治疗难治性和侵袭性疾病的有趣治疗方法，如肝炎三角洲。“

披露：一些研究作者宣布与制药行业有关联。有关作者披露的完整列表，请参阅原始参考。

参考

Loglio A，Ferenci P，Colonia Uceda Renteria S，et al。高剂量myrcludex-b单药治疗hdv相关代偿性肝硬化48周的安全性和有效性：3例患者的病例报告[2019年7月11日在线发表]。 J Hepatol。 DOI：10.1016 / j.jhep.2019.07.003