Lampertico Pietro, Roulot Dominique, Wedemeyer Heiner
Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy; CRC "A. M. and A. Migliavacca" Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
AP-HP, Avicenne Hospital, Liver Unit, Sorbonne Paris Nord University, Bobigny, France; Inserm U955, Team 18, Paris-Est University, Créteil, France.
J Hepatol. 2022 Nov;77(5):1422-1430. doi: 10.1016/j.jhep.2022.06.010. Epub 2022 Jun 22.
Chronic hepatitis D (CHD) is the most severe form of viral hepatitis, characterised by the greatest increase in risk of cirrhosis, hepatic decompensation and hepatocellular carcinoma. Pegylated-interferon-α (pegIFNα), the only off-label therapeutic option, has been available for the last 30 years but is associated with suboptimal response rates and poor tolerability. Among the new treatment strategies under clinical evaluation, the entry inhibitor bulevirtide (BLV) is the only one that has received conditional approval from the European Medicines Agency (EMA); approval was granted in July 2020 for the treatment of adult patients with compensated CHD at a dose of 2 mg daily. Phase II studies and the week 24 interim analysis of a phase III study demonstrated the efficacy and safety of this treatment as a monotherapy or combined with pegIFNα. This favourable profile has been confirmed by recent real-world studies performed in Europe. As a long-term monotherapy, BLV has been successfully used to treat patients with advanced compensated cirrhosis. These encouraging yet preliminary findings must be viewed with caution as many critical issues related to this new antiviral strategy are still poorly understood, as summarised in this review. While waiting for new anti-HBV and anti-HDV drugs to become available for combination studies, BLV treatment is currently the only available anti-HDV therapeutic option that might improve the long-term prognosis of difficult-to-manage patients with CHD.
慢性丁型肝炎（CHD）是最严重的病毒性肝炎形式，其特征是肝硬化、肝失代偿和肝细胞癌风险增加幅度最大。聚乙二醇化干扰素-α（pegIFNα）作为唯一一种未获批准的治疗选择，在过去30年中一直可用，但与疗效欠佳和耐受性差有关。在正在进行临床评估的新治疗策略中，进入抑制剂布列韦肽（BLV）是唯一获得欧洲药品管理局（EMA）有条件批准的药物；2020年7月获批用于治疗代偿性CHD成年患者，每日剂量为2毫克。II期研究以及一项III期研究的第24周中期分析证明了这种治疗作为单一疗法或与pegIFNα联合使用的有效性和安全性。欧洲最近进行的真实世界研究证实了这一良好情况。作为长期单一疗法，BLV已成功用于治疗晚期代偿性肝硬化患者。正如本综述所总结的，由于与这种新抗病毒策略相关的许多关键问题仍知之甚少，这些令人鼓舞但初步的发现必须谨慎看待。在等待新的抗HBV和抗HDV药物用于联合研究之际，BLV治疗目前是唯一可用的抗HDV治疗选择，可能改善难以治疗的CHD患者的长期预后。
