Hepatitis D virus infection: Pathophysiology, epidemiology and treatment. Report from the first international delta cure meeting 2022

Chronic infection with hepatitis delta virus (HDV) affects between 12-20 million people worldwide and represents the most severe form of viral hepatitis, leading to accelerated liver disease progression, cirrhosis and its complications, such as end-stage-liver disease and hepatocellular carcinoma. From the discovery of HDV in 1977 by Prof. Mario Rizzetto, knowledge on the HDV life cycle and mechanisms of viral spread has expanded. However, little is still known about the natural history of the disease, host-viral interactions, and the role of the immune system in HDV persistence. Diagnosis of HDV is still challenging due to a lack of standardised assays, while accurate viral load quantification is needed to assess response and endpoints of antiviral treatment. Until recently, interferon has represented the only treatment option in patients with chronic hepatitis delta; however, it is associated with low efficacy and a high burden of side effects. The discovery of the entry inhibitor bulevirtide has represented a breakthrough in HDV treatment, by demonstrating high rates of viral suppression in phase II and III trials, results which have been confirmed in real-world settings and in patients with compensated advanced liver disease. In the meantime, other compounds (i.e. lonafarnib, new anti-hepatitis B virus drugs) are under development to provide alternative or combined strategies for HDV cure. The first international Delta Cure meeting was organised in Milan in October 2022 with the aim of sharing and disseminating the latest data; this review summarises key takeaway messages from state-of-the-art lectures and research data on HDV.