Infectious Canine Hepatitis

Also known as:

Rubarth's Disease Canine adenovirus infection

Description

Infectious Canine Hepatitis (ICH) is a highly contagious disease of dogs caused by Canine Adenovirus 1 (CAV1). This virus is closely related to Canine Adenovirus 2, which causes respiratory disease.

Canine Adenovirus 1 invades via the oronasal route following excretion in the urine and faeces. Urinary excretion can persist for up to nine months after an active infection, and the virus may also be spread by contaminated fomites. Once established, CAV1 replicates in the cells of the oropharynx before a viraemia causes dissemination to other tissues. A trophism exists for hepatic parenchyma and vascular endothelium: the target organs of CAV1 are therefore the liver, kidney, vascular endothelium and eye.

In the liver, the clinical outcome of CAV1 infection depends on the level of pre-existing immunity. Animals with high antibody titres usually mount an effective neutralising antibody response by day seven post-infection which clears the virus. Outcome is variable when a partial antibody response is mounted four to five days post-infection: both chronic active hepatitis (and ultimately hepatic fibrosis) and latent hepatic infection are possible. Low antibody titres, such as in unvaccinated dogs, fail to prevent infection and pathology and lead to potentially fatal hepatic necrosis. This necrosis is initially widespread and centrilobular, but may progress to become panlobular. In the kidney, virus localisation or deposition of circulating immune complexes causes glomerular damage and thus proteinuria. Immune complexes may also be deposited in the cornea and uveal tract, damaging the eye. In addition to glomerular localisation, CAV1 persists in the renal tubular epithelium which accounts for the extended period of urinary excretion. Virus replication in the vascular endothelium leads to vasculitis and bleeding diatheses, and direct cytoxic damage to the eye is also possible.

Signalment

Young, unvaccinated dogs are most often affected.

Diagnosis

Clinical Signs

Signs may be peracute or acute in onset. In acute cases, the key clinical findings are vomiting, abdominal pain, anorexia, diarrhoea and pyrexia. Some cases may also show signs of a bleeding disorder. However, there are many different features that clinical examination could possibly reveal. These might include:

• Abdominal distension and/or pain
• Hepatomegaly
• Jaundice
• Petechial or ecchymotic haemorrhages
• Epistaxis
• Bleeding from venipuncture sites
• Pneumonia
• Lymphadenopathy
• Pharyngitis or tonsilar enlargement
• CNS signs such as depression, disorientation and seizures.

Clinical signs generally persist for five to seven days before the animal's condition improves. During the recovery phase, 20% of cases develop corneal oedema and anterior uveitis ("blue eye"). In peracute cases, death rapidly follows the onset of clinical signs.

Laboratory Tests

Routine haematology and blood biochemistry may show several changes. Leucocytes are initally depleted due to neutropenia and lymphopenia, but recovering animals display leucocytosis and neutrophilia. The liver enzymes ALT, AST and SAP tend to be raised, and liver function is impaired. This is demonstrated by elevations in bile acids, ammonia and bilirubin. Clotting abnormalities such as thrombocytopaenia and prolonged PT and APTT may also be noted. However, although indicative of heptatic disease, these tests are non-specific for infectious canine hepatitis.

Other laboratory tests may be used in the confirmation of CAV1 infection. Although virus isolation (on tissues or secretions) and immunofluorescence (on infected tissues) are both possible, serology is the most useful adjunctive test. CAV1 antibodies typically increase to levels greater than those post-vaccination during active infection, and so a rising antibody titre can confirm a diagnosis if infectious canine hepatitis.

Radiography

Hepatomegaly may be seen on radiography.

Biopsy

Impression smears made of the liver may be stained to show nuclear inclusion bodies, and centrilobular necrosis is typically seen on liver biopsy. For more information, please see the details on histopathology below.

Pathology

Gross

The liver is enlarged and friable on post-mortem examination. Extensive centrilobular necrosis leads to a pale, mottled appearance, but widespread haemorrhage is also apparent. These haemorrhages are located particularly on the serosal surface. Ascites results from this hepatitis, and fibrinous or fibrino-haemorrhagic adhesions can sometimes be seen between the lobes of the liver.

Other organs may also show changes. For example, the wall of the gall bladder may be oedematous, and lymph nodes can be enlarged, reddened and haemorrhagic. Chronic interstitial nephritis may feature.

Histological

Histopathology reveals centrilobular necrosis. Haematoxylin and eosin staining reveals basophilic intranuclear inclusion bodies in hepatocytes and macrophages. It is possible to use immunofluorescence to stain for viral antigen in vascular endothelium.

Treatment

Control

In an outbreak

• Isolate infected dogs
• Disinfect premises

To prevent

• Vaccination: tissue culture adaptation that may be live or inactivated
• Cross protection with CAV2
• Live vaccines are known to cause keratitis in Afghans, Red Setters and Saluki