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PROFESSIONAL VERSION
Infectious Canine Hepatitis
By Kate E. Creevy , DVM, MS, DACVIM-SAIM, College of Veterinary Medicine & Biomedical Sciences, Texas A & M University; Jeremy B. Evans , DVM, Department of Small Animal Clinical Sciences, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University Reviewed/Revised Nov 2022 | Modified Sept 2024 Adenoviral hepatitis in dogs results in fever, vasculitis and hepatitis, with possible sequelae of coagulopathy and subsequent immune- mediated corneal or renal effects. Most dogs recover but the disease can be fatal. Treatment is supportive; ante-mortem diagnosis is by PCR, ELISA or serology. Vaccination with modified live canine adenovirus-2 is protective against this disease caused by canine adenovirus-1, and is considered a core vaccine. Infectious canine hepatitis (ICH) due to canine adenovirus 1 (CAV-1) is a worldwide, infectious disease of dogs, with clinical signs that vary from a slight fever and congestion of the mucous membranes to severe depression, marked leukopenia, and coagulation disorders. Clinical signs and laboratory abnormalities often relate to the tendency of the virus to cause hepatocellular necrosis and diffuse endothelial cell damage ; however, virus-associated immune complex deposition can also lead to uveitis, corneal clouding, and glomerulonephritis. Diagnosis can be made by the use of ELISA, serologic, or PCR testing, and postmortem diagnostics include identification of intranuclear inclusion bodies in the liver, PCR assay, and/or FISH of infected tissue. Although the disease results from infection by CAV-1, administration of live, attenuated CAV- vaccine results in adequate protection. Supportive care is aimed at maintaining fluid balance, addressing hepatic dysfunction, managing the coagulopathic state, and treating secondary Etiology and Pathogenesis | Clinical Findings | Diagnosis | Treatment | Prevention | Key Points | For More Information
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bacterial infections. The mortality rate ranges from ~10% to 30%; in some surviving dogs, however, organ disease such as hepatitis or glomerulonephritis may persist after recovery. ICH has also been reported in foxes, wolves, coyotes, bears, lynx, and some pinnipeds; other carnivores may become infected without developing clinical illness. The disease has become uncommon in areas where routine immunization is performed; however, periodic outbreaks, which may reflect maintenance of the disease in wild and feral hosts, reinforce the need for continued vaccination. Etiology and Pathogenesis of Infectious Canine Hepatitis Infectious canine hepatitis is due to a nonenveloped DNA virus, canine adenovirus 1 (CAV-1), which is antigenically related to CAV-2 (one of the causes of canine infectious tracheobronchitis). Oronasal exposure to urine, feces, or saliva from infected dogs is the main route of infection. Transmission via either fomites or ectoparasites is also possible. Recovered dogs shed virus in their urine for ≥ 6 months. Initial infection occurs in the tonsillar crypts and regional lymph nodes, followed by viremia and disseminated infection. Vascular endothelial cells are the primary target; hepatic and renal parenchyma, spleen, and lungs become infected as well. Chronic kidney lesions and corneal clouding (blue eye) result from immune-complex reactions after recovery from acute or subclinical disease. Clinical Findings of Infectious Canine Hepatitis Clinical signs of infectious canine hepatitis vary from a slight fever to peracute death. The mortality rate ranges from 10% to 30% and is typically highest in very young dogs. Concurrent parvoviral or distemper infection worsens the prognosis. The incubation period is 4–9 days. The first sign is commonly fever of > 40°C (104°F), which lasts 1–6 days and is usually biphasic. If the fever is of short duration, leukopenia may be the only other sign; if fever persists for > 1 day, however, acute illness develops. Clinical signs may include: nonspecific signs such as lethargy, thirst, or anorexia conjunctivitis, serous oculonasal discharge, or corneal clouding (blue eye) abdominal pain and vomiting, including hematemesis
kidney cortex. Diagnosis of Infectious Canine Hepatitis Clinical evaluation Testing Although clinical signs of infectious canine hepatitis can be nonspecific, any young puppy with evidence of severe hepatic dysfunction, coagulopathy or disseminated intravascular coagulation, or corneal clouding should be considered a suspect for ICH. Commercially available ELISA, serologic, and PCR tests are available to obtain an antemortem diagnosis. Usually, the abrupt onset of illness and bleeding suggest ICH, although clinical evidence is not always sufficient to differentiate ICH from canine distemper. Definitive antemortem diagnosis is not required before supportive care is instituted; however, it can be pursued with commercially available ELISA, serologic, and PCR testing. PCR assay or restriction fragment length polymorphism is required to definitively distinguish CAV-1 from CAV-2, if clinically necessary. Postmortem gross changes in the liver and gallbladder are more conclusive, and diagnosis is confirmed by virus isolation, immunofluorescence, detection of characteristic intranuclear inclusion bodies in the liver, or PCR or fluorescence in situ hybridization analysis of infected tissue. Treatment of Infectious Canine Hepatitis Supportive care The treatment for infectious canine hepatitis is supportive care, which includes the following goals: to provide fluid support (balanced IV electrolyte solutions and dextrose supplementation as necessary) to maintain adequate nutrition to address coagulopathy (plasma and/or whole blood transfusions and/or anticoagulant therapy) to limit secondary bacterial invasion (IV antimicrobials) Although transient corneal opacity (which may occur during the course of ICH or may be
associated with the administration of live, attenuated CAV-1 vaccines) usually requires no treatment, applying atropine ophthalmic ointment may alleviate the painful ciliary spasm sometimes associated with it. Dogs with corneal clouding should be protected against bright light. Systemic corticosteroids are contraindicated for the treatment of corneal opacity associated with ICH. Prevention of Infectious Canine Hepatitis Injectable modified live virus (MLV) vaccines are available and are often combined with other vaccines. Vaccination against infectious canine hepatitis is recommended at the time of canine distemper vaccination. Maternal antibody from immune bitches interferes with active immunization in puppies until they are 9–12 weeks old. Live, attenuated CAV-1 vaccines have produced transient unilateral or bilateral opacities of the cornea, and the virus may be shed in urine. For these reasons, live, attenuated CAV-2 strains, which provide cross-protection against CAV-1, are preferentially administered because they have very little tendency to produce corneal opacities or uveitis, and the virus is not shed in urine. Historically, annual revaccination against ICH was standard, and many vaccines are labeled for annual administration. Increasing evidence suggests that immunity induced by injectable MLV CAV-1 vaccines lasts ≥ 3 years, and labels of some commercial vaccines are beginning to reflect a longer revaccination interval. With regard to disinfection of veterinary premises and kennels, it should be noted that CAV- is durable in the environment, surviving outside the host for weeks or months. It is resistant to lipid solvents (such as ether), as well as to acid and formalin; however, it can be inactivated by steam cleaning or by exposure to a 1%–3% solution of sodium hypochlorite (household bleach). Key Points Infectious canine hepatitis is a viral disease that affects young dogs and can be accompanied by a wide variety of clinical signs, ranging from fever and lethargy to hepatic failure, severe coagulopathy, and death. Diagnosis can be obtained by ELISA, PCR assay, or serologic evaluation, but is
