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 (CAV-1). 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 and spread via fomites. . Once established, CAV-1 replicates in the cells of the oropharynx before a viraemia causes dissemination to other tissues 4-8 days later. A trophism exists for hepatic parenchyma and vascular endothelium. In the liver, CAV-1 replicates in Kuppfer cells and damages adjacent hepatocytes when released. Other parenchymal organs, namely the kidney, and the eye may also be affected in infectious canine hepaptitis. When an adequate antibody response is mounted, organs may be cleared of virus within 10-14 days, but urinary excretion can persist for up to nine months after an active infection.

In the liver, the clinical outcome of CAV-1 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, CAV-1 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

Infectious canine hepatitis affects unvaccinated dogs, particularly those of less than one year of age. There are no breed or sex predispositions.

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 CAV-1 infection. Although virus isolation (on tissues or secretions) and immunofluorescence (on infected tissues) are both possible, serology is the most useful adjunctive test. CAV-1 antibodies typically increase to levels greater than those post-vaccination during active infection, and so a rising antibody titre can confirm a diagnosis of infectious canine hepatitis.

Diagnostic Imaging

Abdominal radiography may show the liver to be large or normally sized, and detail may be lost due to the presence of an effusion. Ultrasonography may show hepatomegaly, multifocal to diffuse hypoechoic areas within the parenchyma, and effusion.

Biopsy

Impression smears made of the liver may be stained with haemotoxylin and eosin to show intranuclear inclusion bodies in hepatocytes and macrophages. These are also seen on histopathology of liver biopsies, in addition to centrilobular necrosis.

Pathology

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 particularly obvious on the serosal surface. This hepatisis leads to ascites, 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 be seen.

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

Treatment for infectious canine hepatitis is supportive and symptomatic. This may include fluid therapy, and blood or plasma in the event of clotting disorders. Heparin may be necessary if disseminated intravascular coagulation arises, and intravenous glucose can be used to correct hypoglycaemia. Hepatic encephalopathy can be treated with lactulose and antibiotics such as neomycin or ampicillin, and S-adenosyl methionine can be provided as a glutathione precursor or replacement to help minimise damage and aid liver regeneration. Anti-emetic drugs can also be used.

Prevention

A vaccine is available for infectious canine hepatitis and is a "core" canine vaccine. The vaccine is a live attenuated strain of CAV-2, which confers cross-protection against CAV-1. The primary course consists of two vaccinations given three to four weeks apart, and boosters are required at least every two to three years.

In an outbreak, isolation, barrier nursing and strict hygiene are necessary to prevent spread of disease.

Prognosis

The prognosis for infectious canine hepatitis is guarded.

References

1. Merck & Co (2008) The Merck Veterinary Manual (Eighth Edition) Merial
2. Tilley, L.P. and Smith, F.W.K.(2004)The 5-minute Veterinary Consult(Third edition) Lippincott, Williams & Wilkins.
3. Carter, GR and Wise, DJ (2005) A Concise Review of Veterinary Virology, International Veterinary Information Service.