Longitudinal observation of chronic domestic cat hepadnavirus infection in cats with evidence of extrahepatic involvement

ObjectivesDomestic cat hepadnavirus (DCHBV), belonging to the <i>Orthohepadnavirus</i> genus and closely related to the human hepatitis B virus (HBV), is detected in domestic cats; however, its disease progression and pathological impact remain unclear. This study investigates the longitudinal dynamics of DCHBV infection in naturally infected cats over a period of up to 310 days after detection, focusing on blood parameters and viral load fluctuations, liver pathology and extrahepatic dissemination.MethodsAmong 87 screened cats, four (4.6%) tested positive for DCHBV using quantitative PCR (qPCR). These cats were monitored longitudinally through repeated health checks, including viral load monitoring. After natural death, necropsy, histopathology, in situ hybridisation (ISH) and immunohistochemistry (IHC) were conducted to assess lesion distribution and viral localisation. Whole-genome sequencing and phylogenetic analysis were also performed on DCHBV-positive cases.ResultsThree of four DCHBV-positive cats exhibited persistent high viremia (>7 log₁₀ genomic copies/ml) for over 6 months. Despite sustained viremia, liver enzyme levels showed variable trends, with some cases maintaining normal alanine aminotransferase and alkaline phosphatase levels. Histopathological analysis revealed various degrees of interface hepatitis, consistent with immune-mediated liver injury. DCHBV DNA was most abundant in the liver and confirmed through qPCR, ISH and IHC. Viral DNA was also detected in extrahepatic tissue, including the spleen, lung and salivary glands. Complete genome sequencing confirmed clustering within genotype A, with low genetic variability. Coinfection with feline leukaemia virus (FeLV) was noted in two cats, which may influence host immune responses.Conclusions and relevancePersistent viremia and liver inflammation suggest DCHBV may contribute to hepatic pathology, likely influenced by host immune responses and coinfections. However, because of the limited number of cases and the presence of FeLV coinfection in some cats, firm conclusions cannot be drawn. These findings provide a foundational basis that warrants confirmation and expansion in larger cohorts.