Hepatitis D Virus Infection: Pathophysiology, Epidemiology and Treatment. Report From the Third Delta Cure Meeting 2024

Abstract

Chronic infection with hepatitis delta virus (HDV) leads to rapid progression of liver disease, cirrhosis and complications such as end-stage liver disease and hepatocellular carcinoma. In recent years, understanding of the HDV life cycle has increased significantly; however, much remains unknown about the pathogenesis, host-virus interactions and the role of the immune system in HDV persistence and control. Challenges remain in the diagnosis of HDV, not only because of the lack of standardised assays, but also because of limited access and availability in resource-limited countries. The improved knowledge of the HDV life cycle has led to the development and approval of the first HDV-direct antiviral, Bulevirtide (BLV). Treatment with BLV shows high rates of viral suppression in clinical trials and real-world studies. Questions remain about the duration of treatment with BLV and the potential benefits of combination therapy with pegylated interferon alpha (PegIFNα). First data from the Phase III study in which BLV was stopped after 3 years of treatment have recently been presented at congresses. Results from the Phase II study evaluating the combination of BLV and PegIFNα, as well as real-world experiences, have been published. Despite recent advances in antiviral treatment, strategies to achieve HBsAg loss, which most closely resembles HDV cure, are not available and antiviral treatment for patients with advanced liver disease is limited. The third international Delta Cure meeting, held in Milan in October 2024, aimed to share the latest findings, and this review highlights key takeaways from the lectures and research on HDV.

Keywords: Bulevirtide; Delta Cure; HDV; HDV RNA; chronic Hepatitis Delta; cirrhosis; entry inhibitor; lonafarnib.