Virological and pathological characterization of an outbreak of domestic cat hepatitis B virus infection in a cat shelter in Japan

Domestic cat hepatitis B virus (DCHBV) infections are associated with chronic hepatitis and hepatic cancer in cats, similar to human HBV. We previously demonstrated that the positivity rate for DCHBV in Japan is less than 1% among tested samples, suggesting lower viral dissemination in Japan than in other countries. Furthermore, the transmission dynamics of DCHBV remain poorly understood. In this study, we document the first recorded outbreak of DCHBV in a cat shelter in Japan, which had an unprecedentedly high prevalence of 26.59% (46/173 cats). We investigated potential transmission routes via quantitative polymerase chain reaction analysis of matched blood, oral, and rectal swab samples. Blood and oral viral loads were significantly correlated, with viral DNA detected in both oral (40.54%) and rectal (19.44%) cavities of viremic cats. Phylogenetic analysis of the polymerase gene retrieved from deceased cats yielded >99.2% sequence identity, indicating the circulation of a single strain. Pathological assessments, including histopathology, immunohistochemistry, and RNA in situ hybridization, confirmed viral presence in hepatocytes and biliary epithelium, linking the outbreak with severe hepatic lesions, including cholangitis, fibrosis, and cholangiocarcinoma. Our findings indicate that the transmission route of DCHBV may be more complex than initially anticipated, underscoring the importance of understanding the mode of transmission to effectively control DCHBV infection, particularly in multi-cat facilities.