Worldwide, about 350 million individuals are chronically infected with HBV1. Thereof, 5% are also infected with HDV, and at risk of developing severe liver inflammation, scarring, and liver cancer1,2. Although the infection is quite under control in the developed world due to preventive HBV vaccination, it is still an issue in developing countries, such as central and northern Africa and parts of Asia3,4. With over 15 million individuals worldwide infected with HDV, the virus represents a major public health concern1. Chronic HDV infection is the most harmful form of chronic viral hepatitis, with the highest mortality rates2,5. Since transmission mainly occurs from infected mother to child at birth or through contact with infected blood and bodily fluids, particularly newborns and intravenous drug users are at risk6. At present, no effective cure for chronic hepatitis delta exists1. The health consequences associated with an HDV infection can result in high healthcare costs and a reduced quality of life. Additionally, the disease may lead to reduced productivity and thus missed workdays, increasing the economic burden even more. By investigating the molecular interactions between HDV, HBV, and their host, being the human hepatocyte, we hope to unravel the immune influencing mechanisms responsible for the immunopathogenesis. Research into these mechanisms could pave the way for the development of new therapeutic strategies, thereby improving the quality of life of those affected5. This may especially be useful for high-risk groups in low-income countries without access to HBV vaccination and where the incidence of HDV infections is high.