Update on the management of HDV infection: current events and perspectives

HDV infection has long been, and continues to be, a significant challenge. Chronic liver disease related to HDV is one of the most aggressive forms of liver disease, carrying a high risk of progression to cirrhosis and decompensated liver disease. Although an estimated 12 to 72 million people worldwide have been exposed to HDV, the prevalence of HDV-related conditions is believed to be underreported, and further epidemiological studies are needed to better understand its scope. In this context, screening for anti-HDV in all HBsAg-positive individuals could help identify undiagnosed cases of HDV, regardless of known risk factors. While certain groups are at higher risk for HDV infection, more than half of individuals with HDV infection have no identifiable risk factors. Simultaneously, the risk factors for severe disease progression remain poorly defined, although persistent and/or high viral load, along with elevated cytolysis indices, appear to be linked to a more severe disease prognosis. Once HDV infection is diagnosed, treatment becomes necessary, especially given the limited therapeutic options available. Until recently, interferon-α was the only treatment option, but it came with challenges, including poor tolerability and suboptimal virological response rates. In July 2020, the European Medicines Agency (EMA) approved Bulevirtide, a new drug for the treatment of HDV. Bulevirtide not only offered a novel therapeutic option for HDV but also marked a milestone in the history of HDV treatment. However, while this new drug represents a significant advance, there are still several aspects that need further clarification and exploration.