Age unknown, sex unknown, red fox (Vulpes vulpes).A free-ranging red fox (Vulpes vulpes) (age and sex not recorded) was submitted to a veterinary practice in Cheshire, England in May 2000. The animal was depressed and exhibited mild jaundice at the time of admission. It died one day later.

Gross Description:  

At necropsy, the fox was mildly jaundiced and had a congested liver, with mild accentuation of the hepatic lobular pattern. The mesenteric and hepatic lymph nodes were mildly enlarged and congested.

Histopathologic Description:

Liver: Histopathologic examination of the liver reveals numerous amphophilic intranuclear inclusion bodies in hepatocytes. Hepatocytes are swollen, mildly vacuolated and dissociated. There is individual degeneration and necrosis of hepatocytes. Hepatic sinusoids are congested and contain fibrin deposits. There is expansion of the space of Diss+â-¬.

Morphologic Diagnosis:  

Hepatocellular degeneration, acute, diffuse, moderate, with numerous intranuclear inclusion bodies, infectious canine hepatitis (canine adenovirus type 1).


Hepatocellular degeneration

Contributor Comment:  

The presence of intranuclear inclusion bodies and degeneration of hepatocytes in this case were consistent with infectious canine hepatitis (ICH), which is caused by canine adenovirus type 1 (CAV-1). Intranuclear inclusion bodies were also observed in renal glomeruli, renal tubular epithelial cells and endothelial cells lining blood vessels. CAV-1 was isolated from a liver sample of the affected red fox.(7)

Spontaneous ICH has been reported mostly in domestic dogs, farmed foxes and other captive carnivores.(7) The disease was first identified in North America in captive silver foxes, a colour variant of the red fox (Vulpes vulpes), and has also has been reported in farmed Arctic (blue) foxes (Alopex lagopus). Red foxes and gray foxes (Urocyon cinereoargenteus) are susceptible to experimental infection with CAV-1. The first case of ICH in a free-ranging gray fox was identified in 2004 in Georgia, USA.(2) The present case represents one of the first recorded cases of ICH in free-ranging red foxes in Europe.(7)

Clinical signs and pathologic findings in red foxes with ICH are similar to those described in other species of foxes and in dogs.(2,7) Clinical signs in foxes appear after an incubation period of 2 to 6 days and may include anorexia, rhinitis, hemorrhagic diarrhea, hyperexcitability, seizures, paralysis, coma and death. Death may occur after a brief clinical course or may occur suddenly without prior clinical signs. Uveitis and keratitis (blue eye) may develop in non-fatal cases of ICH in silver foxes. Gross lesions in foxes with ICH are considered to be less distinctive than in dogs, with generalized congestion and mild enlargement of the liver, spleen and adrenal glands. On histopathologic examination, vasculitis is considered to be a prominent feature of ICH in foxes, but was not a major finding in three red foxes with ICH examined in the United Kingdom.(7) Necrosis of hepatocytes and renal tubular epithelial cells are evident in foxes with ICH, but hepatic necrosis may be less severe than in dogs.

There is serologic evidence of exposure to CAV-1 in free-ranging red and gray foxes in North America, Germany, Australia and the United Kingdom.(1,3,4,7,8) Antibodies against CAV-1 have been detected in serum from 2/57 (3%) free-ranging North American red foxes in Wisconsin, USA, 17/485 (3.5%) free-ranging red foxes in Germany and 308/1326 (23.2%) free-ranging naturalized red foxes in Australia.(1,4,8) Antibodies against canine adenovirus type 1 were detected in postmortem fluid extracts from 11/58 (19%) frozen red fox carcasses from the United Kingdom.(7) Antibodies against CAV-1 have also been detected in 24/27 (88%) free-ranging gray foxes in the USA.(3)

The roles of red and gray foxes in the epidemiology of ICH are uncertain. It is not known if foxes are an important reservoir of infection with CAV-1 and thus a source of infection for domestic dogs, or vice versa.

JPC Diagnosis:  

Liver: Hepatocellular degeneration and necrosis, diffuse, moderate, with numerous hepatocellular viral intranuclear inclusions and sinusoidal fibrin thrombi.

Conference Comment:  

The structural unit of the liver is classically referred to as the hepatic lobule; however, when viewed with respect to its functionality and proximity to the blood supply, it is commonly referred to in the literature as a hepatic acinus. Both the hepatic lobule and acinus are further subdivided anatomically and physiologically into areas or zones. Hepatocytes in zone 1of the acinus are closest to the incoming supply of oxygenated blood; in terms of lobular structure, this is the periportal area. Zone 2 corresponds to mid-zonal hepatocytes. Zone 3 (periacinar) hepatocytes are furthest from the oxygenated blood, and surround the portal vein; from an anatomic standpoint, this area is referred to as centrilobular. A single layer of hepatocytes at the periphery of the lobule forms a histologically distinct zone referred to as the limiting plate.(5)

When examining the liver, the pattern and extent of necrosis, can provide insight into potential etiologies. Necrosis is often classified based on the part(s) of the lobule affected. Centrilobular necrosis is common with viral infection, many toxins, and as cells of this region are the last in the body to receive oxygenated blood, processes resulting in hypoxemia (anemia or circulatory failure) often result in centrilobular necrosis. Pure mid-zonal lesions are extremely rare. Periportal necrosis is indicative of direct-acting toxins that do not need to be metabolized to a toxic intermediate via the cytochrome P450 system.(6)

The World Small Animal Veterinary Association Liver Standardization group published an accepted, standardized nomenclature and corresponding diagnostic criteria of hepatic disease.(5) Within sites of hepatic inflammation, there can be individual apoptotic or necrotic cells referred to as apoptotic or acidophil bodies. Confluent necrosis involves large areas of the liver, may have a random or zonal distribution and, when bridging vasculature structures, is more aptly termed bridging necrosis. When cells in all regions of the acinus/lobule are necrotic, the term massive necrosis is often employed, such as that observed in hepatosis dietetica, cocklebur intoxication and Amanita spp. intoxication. The pattern of piecemeal necrosis is characterized by hepatocyte death at the interface of parenchyma and connective tissue.(5,6)


1. Amundson TE, Yuill TM. Prevalence of selected pathogenic microbial agents in the red fox (Vulpes fulva) and gray fox (Urocyon cinereoargenteus) of southwestern Wisconsin. J Wildl Dis. 1981;17:17-22.
2. Gerhold RW, Allison AB, Temple DL, Chamberlain MJ, Strait KR, Keel MK. Infectious canine hepatitis in a gray fox (Urocyon cinereoargenteus). J Wildl Dis. 2007;43:734-736.
3. Riley SP, Foley J, Chomel B. Exposure to feline and canine pathogens in bobcats and gray foxes in urban and rural zones of a national park in California. J Wildl Dis. 2004;40:11-22.
4. Robinson AJ, Crerar SK, Waight Sharma N, M+â-+ller WJ, Bradley MP. Prevalence of serum antibodies to canine adenovirus and canine herpesvirus in the European red fox (Vulpes vulpes) in Australia. Aust Vet J. 2005;83:356-361.
5. Rothuizen J, Bunch SE, Charles JA, et al. Morphological classification of parenchymal disorders of the canine and feline liver: 1. Normal histology, reversible hepatocytic injury and hepatic amyloidosis; and 2. Hepatocellular death, hepatitis and cirrhosis. In: WSAVA Standards for clinical and histological diagnosis of canine and feline liver disease. St. Louis, MO: Elsevier; 2006:78-79, 85-88.
6. Stalker MJ, Hayes MA. Liver and biliary system. In: Maxie MG, ed. Jubb, Kennedy and Palmers Pathology of Domestic Animals. 5th ed., vol. 2. Philadelphia, PA: Elsevier Ltd; 2007:320-322.
7. Thompson H, OKeeffe AM, Lewis JCM, Stocker LR, Laurenson MK, Philbey AW. Infectious canine hepatitis in red foxes (Vulpes vulpes) in the United Kingdom. Vet Rec. 2010;166:111-114.
8. Truyen U, M+â-+ller T, Heidrich R, Tackmann K, Carmichael LE. Survey on viral pathogens in wild red foxes (Vulpes vulpes) in Germany with emphasis on parvoviruses and analysis of a DNA sequence from a red fox parvovirus. Epidemiol Infect. 1998;121:433-440.

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