A novel hepadnavirus is associated with chronic hepatitis and hepatocellular carcinoma in cats

Patricia A. Pesavento, Kenneth Jackson, Timothy Scase, Tiffany Tse, Bronte Hampson, John S. Munday, Vanessa R. Barrs, Julia A. Beatty

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Abstract

In 2015, over 850,000 people died from chronic hepatitis and hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV). A novel hepatitis B-like virus has recently been identified in domestic cats. The pathogenic potential of domestic cat hepadnavirus (DCH), for which 6.5% to 10.8% of pet cats are viremic, is unknown. We evaluated stored formalin-fixed, paraffin-embedded biopsies of diseased and normal feline liver for the presence of DCH using PCR and in situ hybridization (ISH). DCH was detected in 43% (6/14) of chronic hepatitis cases and 28% (8/29) of HCCs, whereas cholangitis (n = 6), biliary carcinoma (n = 18) and normal liver (n = 15) all tested negative for DCH. Furthermore, in DCH-associated cases, the histologic features of inflammation and neoplasia, and the viral distribution on ISH were strikingly similar to those seen with HBV-associated disease. Several histological features common in human HBV-associated hepatitis, including piecemeal necrosis and apoptotic bodies, were identified in DCH-positive cases of chronic hepatitis. In two cases of HCC examined, the proliferation index in regions that were ISH-positive was higher than in ISH-negative regions. The intracellular distribution of virus in both hepatitis and HCC demonstrated that viral nucleic acid is present in both nuclear and cytoplasmic forms. Collectively, these findings demonstrate a compelling association between DCH and some cases of chronic hepatitis and hepatocellular carcinoma in the cat that mirrors features of HBV-associated hepatopathies. Future investigations of viral epidemiology and natural history are needed to establish the impact of DCH on feline health.

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Keywords

  • Cancer
  • Cat
  • Disease
  • Feline
  • HBV
  • HCC
  • Hepatology
  • Oncogenesis
  • Orthohepadnavirus
  • Pathology
  • Viral

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

Cite this

Pesavento, P. A., Jackson, K., Scase, T., Tse, T., Hampson, B., Munday, J. S., Barrs, V. R., & Beatty, J. A. (2019). A novel hepadnavirus is associated with chronic hepatitis and hepatocellular carcinoma in cats. Viruses, 11(10), [969]. https://doi.org/10.3390/v11100969