1Foundation 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. Electronic address: email@example.com.
2AP-HP, Avicenne Hospital, Liver Unit, Sorbonne Paris Nord University, Bobigny, France; Inserm U955, team 18, Paris-Est University, Créteil, France.
3Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover, Germany; Excellence Cluster RESIST, Hannover Medical School; German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig.
Chronic hepatitis D (CHD) is the most severe form of viral hepatitis, displaying a superior risk of cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC). Pegylated-Interferon α (pegIFNα), the only off-label therapeutic option that has been available for the last 30 years, has suboptimal response rates and it is poorly tolerated. Among the new treatment strategies under clinical evaluation, the entry inhibitor bulevirtide (BLV) is the only that received conditional approval from the European Medicines Agency (EMA) in July 2020, at the dose of 2mg daily, for the treatment of adult patients with compensated CHD. Phase II studies and the week 24 interim analysis of phase III study demonstrated the efficacy and safety of this treatment as a monotherapy or combined with pegIFNα. This favorable profile has been confirmed by recent real-world studies performed in EU. As a long-term monotherapy, BLV has been successfully used to treat patients with advanced compensated cirrhosis. These encouraging yet preliminary findings must be taken with caution as many critical issues related to this new antiviral strategy are still poorly understood as summarized by this review. While waiting for new anti-HBV and anti-HDV drugs to become available for combination studies, BLV treatment is the only currently available anti-HDV therapeutic option that might improve the long-term prognosis of difficult-to-manage patients such as those with CHD.