Canine Hepatitis Study Guide

Overview and Clinical Importance

Hepatitis refers to inflammation of the liver and represents a significant category of hepatobiliary disease in dogs. The liver has remarkable regenerative capacity, but when injury exceeds repair mechanisms, hepatitis can progress to fibrosis, cirrhosis, and ultimately hepatic failure. Understanding the etiology, clinical presentation, and management of canine hepatitis is essential for the NAVLE examination.

Canine hepatitis can be classified as acute (rapid onset, typically days to weeks) or chronic (progressive damage over weeks to months, characterized by fibrosis). The 2019 ACVIM Consensus Statement provides standardized criteria for diagnosis and treatment of chronic hepatitis in dogs.

Classification of Canine Hepatitis

Canine hepatitis can be classified by duration (acute vs. chronic), etiology (infectious, toxic, metabolic, immune-mediated, idiopathic), and histopathologic pattern. The WSAVA Liver Standardization Group has established criteria for histologic classification.

Infectious Canine Hepatitis (ICH)

Etiology and Epidemiology

Infectious canine hepatitis (ICH) is caused by Canine Adenovirus Type 1 (CAV-1), a DNA virus distinct from CAV-2 (causes respiratory disease/kennel cough). ICH was first comprehensively described by Rubarth in 1947. The disease is now rare in vaccinated populations due to widespread use of highly effective CAV-2 vaccines, which provide cross-protection against CAV-1.

Key Epidemiologic Features

• Primarily affects unvaccinated dogs, especially puppies less than 1 year old
• Wild canids (foxes, wolves, coyotes) and bears serve as reservoir hosts
• Transmission: oronasal exposure to infected urine, feces, saliva, or nasal discharge
• Recovered dogs shed virus in urine for 6-9 months or longer
• Virus is highly resistant to environmental inactivation; survives on fomites

Pathogenesis

Following oronasal exposure, CAV-1 initially replicates in the tonsillar crypts and regional lymph nodes. Viremia develops within 4-8 days, leading to dissemination to hepatocytes and vascular endothelial cells (primary target cells). The virus also targets the kidneys, spleen, and lungs.

Pathophysiologic Consequences

• Hepatocyte injury: Causes acute hepatic necrosis, particularly centrilobular to bridging patterns
• Endothelial damage: Results in DIC, widespread petechiation ("paint brush" hemorrhages)
• Corneal edema ("blue eye"): Immune-complex deposition in corneal endothelium; occurs 7-10 days post-recovery in approximately 25% of dogs
• Glomerulonephritis: Immune-complex mediated; develops 1-2 weeks after acute signs resolve

Clinical Signs

The incubation period is 4-9 days. Clinical presentation varies from subclinical to peracute fatal disease. Three overlapping syndromes are recognized:

Diagnosis

Clinical Pathology Findings

• Leukopenia: Neutropenia and lymphopenia early; neutrophilic leukocytosis during recovery
• Liver enzymes: Markedly increased ALT and AST (hepatocellular injury); increased ALP
• Coagulation: Thrombocytopenia, prolonged PT and aPTT, increased fibrin degradation products (DIC)
• Urinalysis: Proteinuria is common
• Hypoglycemia: May occur in severe cases

Histopathology

The hallmark finding is centrilobular to bridging hepatic necrosis with large basophilic to amphophilic intranuclear inclusion bodies (Cowdry type A) in hepatocytes and Kupffer cells.

Treatment and Prevention

Treatment is supportive and symptomatic; there is no specific antiviral therapy. Management includes IV fluid therapy, blood product transfusion for coagulopathy/DIC, antiemetics, hepatoprotectants (SAMe, ursodiol, vitamin E), and nutritional support.

Chronic Hepatitis in Dogs

Definition and Histopathologic Criteria

Chronic hepatitis (CH) is defined histopathologically by the WSAVA Liver Standardization Group as the presence of: (1) hepatocellular apoptosis or necrosis, (2) mononuclear or mixed inflammatory cell infiltrate (primarily lymphocytes and plasma cells), (3) regeneration, and (4) fibrosis (the defining feature of chronicity).

Etiology

Copper-Associated Hepatitis (CuCH)

Copper-associated hepatitis is the most common identifiable cause of toxic chronic hepatitis in dogs. Normal hepatic copper concentration is 120-400 micrograms/g dry weight; concentrations greater than 600 micrograms/g are potentially harmful.

Breed Predispositions to Copper-Associated Hepatitis

Other Etiologies

• Drug-induced: Phenobarbital, primidone, phenytoin, lomustine, carprofen, amiodarone
• Infectious: Leptospirosis (can cause chronic pyogranulomatous response), leishmaniasis
• Toxins: Aflatoxin (from Aspergillus in moldy food), cycasin (sago palm)
• Idiopathic/Immune-mediated: Most common; responds to immunosuppression

Clinical Presentation

Chronic hepatitis has a long subclinical phase; up to 20% of dogs with CH have elevated liver enzymes without clinical illness.

• Early/Mild disease: Lethargy, inappetence, weight loss, cyclic illness, vomiting
• Advanced disease: Icterus, ascites, polyuria/polydipsia, coagulopathy
• End-stage (cirrhosis): Hepatic encephalopathy, microhepatica, acquired portosystemic shunts

Diagnostic Approach

Liver Enzyme Interpretation

Diagnostic Imaging

Ultrasonography is the preferred imaging modality but has significant limitations: mild/early CH may have normal findings, and no definitive changes correlate specifically with CH.

Liver Biopsy

Liver biopsy is ESSENTIAL for definitive diagnosis of chronic hepatitis. Fine-needle aspiration (FNA) is NOT adequate for diagnosing inflammatory liver disease. Laparoscopic biopsy is preferred, providing large samples with 16-18 portal triads.

Treatment of Canine Hepatitis

Treatment of Copper-Associated Hepatitis

Treatment of Idiopathic/Immune-Mediated CH

Prognosis

Median survival times for dogs with chronic hepatitis range from 18 months to 3 years. Negative prognostic factors include ascites, hypoalbuminemia, hypoglycemia, prolonged clotting times, bridging fibrosis/cirrhosis, and hepatic encephalopathy.