Changing Pattern of HDV Infection in Italy Over 40 Years; the Current Scenario and the Impending Challenge

Since the initial description of HDV, in the last four decades Italy has witnessed a profound decline of the infection driven by HBV vaccination, contrasted however by the reconstitution of a viral reservoir through migratory flows from endemic HDV areas; in parallel, the medical scenario has changed, resulting in different clinical outcomes. The epidemiological and clinical changes were documented by national surveys performed up to 2025, which provided an ongoing perspective on the long-term evolution of HDV, highlighting the temporal trends in prevalence, risk factors, and clinical features. This review summarises the changes over time of HDV in Italy and the contemporary epidemiologic features of an infection that is vanishing among natives but increasing among migrants, outlining the medical challenge of a new heterogeneous clinical spectrum, including indolent phenotypes.