A Novel Hepadnavirus is Associated with Chronic Hepatitis and Hepatocellular Carcinoma in Cats

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 cat...

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Main Authors: Patricia A. Pesavento, Kenneth Jackson, Timothy Scase, Tiffany Tse, Bronte Hampson, John S. Munday, Vanessa R. Barrs, Julia A. Beatty
Format: Article
Language:English
Published: MDPI AG 2019-10-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/11/10/969
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author Patricia A. Pesavento
Kenneth Jackson
Timothy Scase
Tiffany Tse
Bronte Hampson
John S. Munday
Vanessa R. Barrs
Julia A. Beatty
author_facet Patricia A. Pesavento
Kenneth Jackson
Timothy Scase
Tiffany Tse
Bronte Hampson
John S. Munday
Vanessa R. Barrs
Julia A. Beatty
author_sort Patricia A. Pesavento
collection DOAJ
description 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 (<i>n</i> = 6), biliary carcinoma (<i>n</i> = 18) and normal liver (<i>n</i> = 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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spelling doaj.art-451b4f0bd6be423192de59f5d644e5602022-12-21T19:49:11ZengMDPI AGViruses1999-49152019-10-01111096910.3390/v11100969v11100969A Novel Hepadnavirus is Associated with Chronic Hepatitis and Hepatocellular Carcinoma in CatsPatricia A. Pesavento0Kenneth Jackson1Timothy Scase2Tiffany Tse3Bronte Hampson4John S. Munday5Vanessa R. Barrs6Julia A. Beatty7Department of Pathology Microbiology and Immunology, UC Davis, Davis, CA 95616, USADepartment of Pathology Microbiology and Immunology, UC Davis, Davis, CA 95616, USABridge Pathology, Bristol BS7 0BJ, UKDepartment of Pathology Microbiology and Immunology, UC Davis, Davis, CA 95616, USAFaculty of Science, Sydney School of Veterinary Science, University of Sydney, Camperdown, NSW 2006, AustraliaSchool of Veterinary Science, Massey University, Palmerston North 4410, New ZealandFaculty of Science, Sydney School of Veterinary Science, University of Sydney, Camperdown, NSW 2006, AustraliaFaculty of Science, Sydney School of Veterinary Science, University of Sydney, Camperdown, NSW 2006, AustraliaIn 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 (<i>n</i> = 6), biliary carcinoma (<i>n</i> = 18) and normal liver (<i>n</i> = 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.https://www.mdpi.com/1999-4915/11/10/969felinecancerviralcathbvhccdiseaseoncogenesispathology<i>orthohepadnavirus</i>hepatology
spellingShingle Patricia A. Pesavento
Kenneth Jackson
Timothy Scase
Tiffany Tse
Bronte Hampson
John S. Munday
Vanessa R. Barrs
Julia A. Beatty
A Novel Hepadnavirus is Associated with Chronic Hepatitis and Hepatocellular Carcinoma in Cats
Viruses
feline
cancer
viral
cat
hbv
hcc
disease
oncogenesis
pathology
<i>orthohepadnavirus</i>
hepatology
title A Novel Hepadnavirus is Associated with Chronic Hepatitis and Hepatocellular Carcinoma in Cats
title_full A Novel Hepadnavirus is Associated with Chronic Hepatitis and Hepatocellular Carcinoma in Cats
title_fullStr A Novel Hepadnavirus is Associated with Chronic Hepatitis and Hepatocellular Carcinoma in Cats
title_full_unstemmed A Novel Hepadnavirus is Associated with Chronic Hepatitis and Hepatocellular Carcinoma in Cats
title_short A Novel Hepadnavirus is Associated with Chronic Hepatitis and Hepatocellular Carcinoma in Cats
title_sort novel hepadnavirus is associated with chronic hepatitis and hepatocellular carcinoma in cats
topic feline
cancer
viral
cat
hbv
hcc
disease
oncogenesis
pathology
<i>orthohepadnavirus</i>
hepatology
url https://www.mdpi.com/1999-4915/11/10/969
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