Chronic hepatitis D (CHD) is the most severe form of viral hepatitis, carrying a greater risk of developing cirrhosis and its complications. For decades, pegylated interferon alpha (PegIFN-α) has represented the only therapeutic option, with limited virological response rates and poor tolerability. In 2020, the European Medicines Agency approved bulevirtide (BLV) at 2 mg/day, an entry inhibitor of hepatitis B virus (HBV)/hepatitis delta virus (HDV), which proved to be safe and effective as a monotherapy for up to 144 weeks in clinical trials and real-life studies, including patients with cirrhosis. Long-term BLV monotherapy may reduce decompensating events in patients with cirrhosis. The combination of BLV 2 mg with PegIFN-α increased the HDV RNA undetectability rates on-therapy but not off-therapy, compared with PegIFN monotherapy. However, combination therapy, but not BLV monotherapy, may induce hepatitis B surface antigen (HBsAg) loss in some patients. The PegIFN lambda study has been discontinued due to liver toxicity issues, while lonafarnib boosted with ritonavir showed limited off-therapy efficacy in a phase 3 study. Nucleic acid polymer-based therapy is promising but large studies are still lacking. New controlled trial data come from molecules, such as monoclonal antibodies and/or small interfering RNA, that target HBsAg or HBV RNAs, which demonstrated not only profound HDV suppression, but also HBsAg decline. While waiting for new compounds to be approved as monotherapy or in combination, BLV monotherapy 2 mg/day remains the only approved therapy for CHD, at least in the European Union region.

中文翻译：

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慢性肝炎 delta 的抗病毒治疗：来自临床试验和现实生活研究的新见解


慢性丁型肝炎 （CHD） 是最严重的病毒性肝炎，患肝硬化及其并发症的风险更大。几十年来，聚乙二醇干扰素 α （PegIFN-α） 一直是唯一的治疗选择，病毒学反应率有限且耐受性差。2020 年，欧洲药品管理局批准了 2 毫克/天的布利韦肽 （BLV），这是一种乙型肝炎病毒 （HBV）/丁型肝炎病毒 （HDV） 的入门抑制剂，在临床试验和现实生活中被证明作为单一疗法长达 144 周是安全有效的，包括肝硬化患者。长期 BLV 单药治疗可减少肝硬化患者的失代偿事件。与 PegIFN 单药治疗相比，BLV 2 mg 与 PegIFN-α 的组合增加了治疗中 HDV RNA 的检测不到率，但未增加治疗后 HDV RNA 的检测不到率。然而，联合治疗（而非 BLV 单药治疗）可能会诱导某些患者的乙型肝炎表面抗原 （HBsAg） 丢失。由于肝毒性问题，PegIFN lambda 研究已停止，而利托那韦加强的 lonafarnib 在 3 期研究中显示出有限的停药疗效。基于核酸聚合物的疗法很有前途，但仍然缺乏大型研究。新的对照试验数据来自靶向 HBsAg 或 HBV RNA 的分子，例如单克隆抗体和/或小干扰 RNA，这些分子不仅表明 HDV 受到严重抑制，而且 HBsAg 也下降。在等待新化合物被批准作为单一疗法或联合疗法的同时，BLV 单药治疗 2 mg/d 仍然是唯一获批的 CHD 疗法，至少在欧盟地区是这样。