Advances and challenges in managing hepatitis D virus

Abstract

Background. Hepatitis D virus (HDV) infection, dependent on Hepatitis B virus (HBV) for replication, causes the most aggressive form of chronic viral hepatitis. Despite its significant clinical impact, HDV remains underdiagnosed and is often neglected in both clinical practice and public health strategies. Objective(s). To evaluate advances in HDV diagnosis and treatment, identify key challenges in clinical management, assess public health strategies to enhance detection, care and prevention of infection. Materials and methods. This narrative review is based on an extensive analysis of peerreviewed literature published between 2015 and 2025. Sources include PubMed, EASL and AASLD clinical guidelines, and findings from clinical trials evaluating both antiviral agents and host-targeted therapeutic approaches for the treatment and long-term management of HDV infection. Results. Recent years have seen significant progress in managing HDV. The approval of bulevirtide, an entry inhibitor targeting NTCP (sodium taurocholate co-transporting polypeptide), is the first specific antiviral therapy for chronic HDV infection. Advances in diagnostics, including HDV RNA quantification and improved serological tests, have enhanced early detection and disease monitoring. Despite this, challenges remain: low global testing rates, limited physician awareness, restricted treatment access, and no effective curative combination therapy. A comprehensive multipronged approach is essential to reduce HDV’s global burden. Conclusion(s). Despite recent diagnostic and therapeutic advances, hepatitis D virus remains one of the major clinical challenges. Reducing its global burden requires improved awareness, broader access to diagnostics and treatment, and continued research into effective combination therapies.