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 作者: StephenW 时间: 2019-8-28 11:15
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