Current perspective on hepatitis D: from pathogenesis to novel therapeutics

Hepatitis D (HD) is a severe infectious liver disease caused by a defective RNA virus, the hepatitis D virus (HDV), whose replication is obligately dependent on the hepatitis B virus (HBV), which provides envelope proteins. The disease is associated with a high risk of rapid progression to cirrhosis and hepatocellular carcinoma. The aim of this lecture is to provide a comprehensive overview of current data on the epidemiology, pathogenesis, diagnosis, and treatment approaches for hepatitis D, as well as to highlight key unresolved questions in this field. The lecture summarizes key aspects of the disease. It examines the biology of HDV and its obligate dependence on HBV, which defines a unique pathogenesis involving direct cytopathic and immune-mediated damage. Current epidemiological data are presented, indicating a significant and often hidden global disease burden. Diagnostic algorithms, their capabilities and limitations related to viral variability, are described. The evolution of therapy from interferons to novel targeted drugs is highlighted, along with the role and limitations of HBV vaccination as the primary preventive measure. The lecture emphasizes that effective control of HD requires a comprehensive approach combining the development of specific antiviral therapy, the expansion of diagnostic screening, and the steadfast strengthening of global HBV vaccination programs. Thus, the key challenge lies in the need to combine the global expansion of simple and effective prevention with the development of fundamentally new, more effective treatment and diagnostic methods for millions of already infected patients.

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