Overview

• Viral disease of dogs (Canidae) caused by CAV-1 serologically homogeneous and antigenically distinct from respiratory CAV-2.
• Infection-targets parenchymal organs (especially liver), eyes, and endothelium.
• Oronasal exposure-viremia (4–8 days); virus shed in saliva and feces; initial dispersal to hepatic macrophages (hepatic Kupffer cells) and endothelium; replicates in Kupffer cells; damages adjacent hepatocytes producing massive viremia when released.
• Adequate antibody response clears organs in 10–14 days; virus persists in renal tubules and may be shed in urine for 6–9 months.
• Chronic hepatitis-after infection in dogs with only partial neutralizing antibody response.
• Cytotoxic ocular injury-anterior uveitis; leads to classic “hepatitis blue eye”. Develops in ∼ 1% of dogs after MLV vaccine.
• Virus can be shed for 6–9 mths in urine.

Signalment

• Dogs and other Canidae
• No breed or sex predilections
• Most common in dogs <1 year of age

Signs

• Depend on immunologic status of host and degree of initial cytotoxic injury.
• Peracute-fever; CNS signs; vascular collapse; DIC; death within hours.
• Acute-fever; anorexia; lethargy; vomiting; diarrhea; hepatomegaly; abdominal pain; abdominal effusion; vasculitis (petechia, bruising); DIC; lymphadenopathy; rarely, nonsuppurative encephalitis.
• Uncomplicated-lethargy; anorexia; transient fever; tonsillitis; vomiting; diarrhea; lymphadenopathy; hepatomegaly; abdominal pain.
• Late-20% of cases develop anterior uveitis and corneal edema 4–6 days post-infection; recover within 21 days; may progress to glaucoma and corneal ulceration. May be the only clinical feature of inapparent infection.

Causes & Risk Factors

• CAV-1
• Unvaccinated dogs susceptible

Differential Diagnosis

• Canine herpesvirus (neonatal)
• Other infectious hepatopathies
• Leptospirosis
• Granulomatous hepatitis
• Toxic hepatitis
• Fulminant infectious disease-e.g., parvovirus, canine distemper

CBC/Biochemistry/Urinalysis

• CBC-schistocytes; leukopenia during acute viremia, followed by leukocytosis with reactive lymphocytosis and nucleated RBCs.
• Biochemistry-liver enzyme activity high initially, begin to decline within 14 days; low glucose and albumin reflect fulminant hepatic failure, vasculitis, and endotoxemia; low sodium and potassium levels reflect GI losses; hyperbilirubinemia if survive several days.
• Urinalysis-proteinuria (glomerular injury); granular casts (renal tubule damage); bilirubinuria consistent with jaundice.

Other Laboratory Tests

• Coagulation tests-reflect severity of liver injury and DIC.
• Serology for antibodies to CAV-1-fourfold rise in IgM and IgG; recent vaccine-induced antibodies confuse interpretation.
• Viral isolation-anterior segment of eye, kidney, tonsil, and urine; difficult in parenchymal organs (especially liver) unless first week of infection.

Imaging

• Abdominal radiography-normal or large liver; poor detail due to effusion.
• Abdominal ultrasonography-may observe hepatomegaly, hypoechoic parenchyma (multifocal or diffuse pattern), and effusion.

Diagnostic Procedures

• Liver biopsy, cytologically evident intranuclear hepatocyte inclusions-aspirates
• Viral culture
• Acute and convalescent serology

Pathologic Findings

• Acute-edema and hemorrhage of lymph nodes; serosal visceral hemorrhages; liver large, dark-mottled; edematous gallbladder; fibrinous exudate on liver, gallbladder, and other viscera; splenomegaly; renal infarcts; abdominal effusion. Perivascular necrosis in liver and other organs; widespread centrilobular to panlobular necrosis. Liver is discolored; abdominal effusion also observed in canine herpesvirus in neonates.
• Chronic-small, fibrotic or cirrhotic liver.

Drug(s)

• Prophylactic antimicrobials-transmural passage of enteric bacteria/and endotoxemia with hepatic failure; e.g., ticarcillin (33–50 mg/kg q6–8h) combined with metronidazole (reduce conventional dose to 7.5 mg/kg IV q8–12h) and fluoroquinolone.
• Antiemetics-metoclopramide (0.2–0.5 mg/kg PO or SC q6–8h or CRI); ondansetron (0.5–1.0 mg/kg PO q12h); maropitant (1 mg/kg/day SC).
• Gastroprotection-H₂-receptor antagonists (e.g., famotidine 0.5 mg/kg PO, IV, SC q12–24h) and sucralfate (0.25–1.0 g PO q8–12h).
• Manage HE (see Hepatic Encephalopathy).
• Ursodeoxycholic acid-choleretic and hepatoprotectant (10–15 mg/kg daily in two divided doses, with food); give indefinitely if chronic hepatitis.
• Antioxidants-vitamin E (10 IU/kg/day PO), N-acetylcysteine IV (140 mg/kg load, then 70 mg/kg q8h) until PO route possible; transition to S-adenosylmethionine (SAMe, 20 mg/kg/day PO, dose on empty stomach) when patient can tolerate oral medications until liver enzymes normalize or indefinitely if chronic hepatitis.

Contraindications

Consider severity of liver injury, protein depletion, and age in calculating drug dosages.

Patient Monitoring

• Monitor fluid, electrolyte, acid-base, and coagulation status to adjust supportive measures.
• Monitor for acute renal failure.

Prevention/Avoidance

MLV vaccination-at 6–8 weeks of age; two boosters 3–4 weeks apart until 16 weeks of age; booster at 1 year; highly effective vaccine; boosters may not be needed.

Possible Complications

• Fulminant hepatic failure
• Hepatic encephalopathy
• Septicemia
• Acute renal failure
• DIC
• Glaucoma
• Chronic hepatitis

Expected Course and Prognosis

• Peracute-poor prognosis; death within hours.
• Acute-variable: guarded to good prognosis.
• Poor antibody response (titer 1:16–1:50)-chronic hepatitis may develop.
• Good antibody response (titer >1:500 IgG)-complete recovery in 5–7 days possible.
• Recovered patients-may develop chronic liver or renal disease.

Age-Related Factors

• Maternal antibody-may protect some pups for first 8 weeks; depends on maternal antibody concentration and efficacy of passive transfer.
• Vaccination of pups with high levels of passively acquired antibodies-successful at 14–16 weeks of age.

See Also

• Herpesvirus Infection-Dogs
• Disseminated Intravascular Coagulation
• Hepatic Encephalopathy
• Hepatic Failure, Acute
• Renal Failure, Acute
• Chronic Hepatitis
• Uveitis

Abbreviations

• CAV-1 = canine adenovirus-1
• CRI = constant rate infusion
• GSH = glutathione
• HE = hepatic encephalopathy
• MLV = modified live virus