Family cluster screening may help identify hepatitis D virus infections among individuals from highly endemic regions.

Hepatitis D virus (HDV) infection is the most severe form of chronic viral hepatitis and may remain substantially underdiagnosed, particularly among individuals originating from highly endemic regions. We report a Romanian family cluster identified through cascade screening following the diagnosis of an index case living in Spain. Six household contacts and first-degree relatives underwent hepatitis B virus (HBV) and HDV screening, identifying three additional cases of chronic HDV infection. Notably, all affected individuals had advanced liver disease at diagnosis, and two subsequently required liver transplantation. Two patients reported having been aware of their HBV diagnosis but were no longer engaged to healthcare follow-up and had not undergone HDV screening. This family cluster highlights the potential value of cascade screening of household contacts and first-degree relatives for identifying HDV infection, particularly among families originating from HDV-endemic regions. It also illustrates the clinical consequences of delayed diagnosis, including presentation with advanced liver disease and limited therapeutic opportunities. Family cluster case-finding could therefore represent a useful complementary strategy to systematic HDV screening in at-risk populations.