Viral Diseases

Viral diseases associated with liver dysfunction include infectious canine hepatitis, canine herpesvirus, inadvertent parenteral injection of an intranasal Bordetella bronchiseptica vaccine in dogs, feline infectious peritonitis, and virulent systemic calicivirus infection in cats. Rarely, canine parvovirus can lead to hepatic injury as a result of portal systemic sepsis.

Infectious canine hepatitis is caused by canine adenovirus 1 (CAV-1). In addition to acute hepatic necrosis, chronic hepatitis and hepatic fibrosis can be sequelae if neutralizing antibody is inadequate to eliminate the infection during the active phase. see Infectious Canine Hepatitis for clinical findings, diagnosis, treatment, and control.

Canine herpesvirus affects neonatal puppies, causing hepatic necrosis as well as other systemic changes. It is usually fatal in puppies.

Accidental parenteral injection of intranasal B bronchiseptica vaccine in dogs can cause both a local inflammatory reaction at the injection site and acute, nonseptic hepatocellular degeneration and necrosis that evolves into chronic hepatitis. There is no known treatment other than symptomatic therapy for chronic inflammatory liver disease.

Feline infectious peritonitis virus is a coronavirus that causes diffuse pyogranulomatous inflammation and vasculitis. Icterus, abdominal effusion, vomiting, diarrhea, and fever are common clinical signs. see Feline Infectious Peritonitis for clinical findings, diagnosis, treatment, and control.

Virulent systemic calicivirus, a recently emerged variant of feline calicivirus, can have mortality rates of 33–60% in adult cats. Primarily identified in shelter or cattery populations, this virus causes profound fever, anorexia, marked subcutaneous edema (limbs and face especially), jaundice, alopecia, and crusting and ulceration of the nose, lips, ears and feet. Adult cats are most severely affected. Individual hepatocyte necrosis ranging to centrilobular or more extensive necrosis is associated with neutrophilic inflammatory foci and intrasinusoidal fibrin deposits.

Bacterial Diseases

Leptospirosis

Infections with Leptospira interrogans serovars icterohemorrhagiae and pomona and chronic infections with grippotyphosa have been associated with liver disease. Other serotypes may also involve the liver. No specific histologic lesions are pathognomonic. Markedly increased liver enzyme activity and marked hyperbilirubinemia indicate hepatic involvement. However, these markers may reflect hepatic response to a sepsis syndrome rather than specific organ invasion in acutely ill dogs. Clinical and clinicopathologic features of liver involvement may worsen initially with treatment (fever, liver enzymes, hyperbilirubinemia). Diagnosis depends on demonstrating a rise in convalescent titer or PCR detection in blood or urine. Identification of organisms in stained liver specimens is difficult. Treatment includes supportive care and specific antibiotic therapy. Penicillins are used initially for the acute phase, (eg, ampicillin [22 mg/kg, IV, qid] or amoxicillin [22 mg/kg, PO, bid]). Aminoglycosides or doxycycline (5 mg/kg, PO, bid for 4 wk) are recommended to treat the carrier phase. Special precautions are recommended when handling animals suspected of having leptospirosis (and their urine specimens) because of the zoonotic potential. (see Leptospirosis.)

Tyzzer's disease

Tyzzer's disease (see Tyzzer's Disease) is a rare but fatal condition caused by Clostridium piliformis. Infections in dogs or cats most commonly occur in immunocompromised hosts, either neonatal animals or adults affected with other conditions. Because C piliforme is a commensal organism in the intestines of laboratory rodents, infection is acquired by contact with or ingestion of rodent feces transporting bacterial spores. Clinical signs (lethargy, anorexia, abdominal discomfort), are acute in onset and illness rapidly progresses to death within 24–48 hr. Marked increase in ALT activity immediately precedes death. Special stains are needed to identify organisms in liver tissue, organisms do not grow in routine bacterial culture media. While there is no effective treatment, a vaccine has been developed for research colony animals.

Mycobacterium avium Infection

Hepatic infection with disseminated M avium has been described in young Abyssinian and Somali cats that have an apparent innate immunodeficiency (unknown cause). The clinical course includes vague illness characterized by a several month history of weight loss in the face of polyphagia. A marked diffuse interstitial pulmonary infiltrate is found in cats with and without respiratory signs. Hepatomegaly and increased ALT and AST activities are notable. Liver samples reveal a granulomatous inflammatory reaction. Treatment including clarithromycin (62.4 mg/cat, PO) combined with either clofazimine (25 mg/cat, PO, sid or 50 mg/cat, PO, every other day) or rifampicin (75 mg/cat, PO) and a fluoroquinolone or doxycycline (50 mg, PO, bid) has achieved remission in affected cats. Relapse should be expected because of the immunocompromised status of these patients.

Extrahepatic and Intrahepatic Bacterial Infections and Sepsis

Extrahepatic infection and sepsis can cause cholestasis and hyperbilirubinemia. Increases in serum bilirubin levels are often moderate to marked, while increases in liver enzyme activity may be only modest. This type of jaundice has been observed in dogs with leptospirosis and cats with ill-defined sepsis. Appropriate treatment targets the underlying septic condition. Increased liver enzyme activity in septicemia/sepsis also can reflect bacterial invasion of liver or hepatocellular damage caused by fever or hypoxia.

Animals with acute hepatic failure and chronic hepatobiliary disease are predisposed to systemic bacterial infection and endotoxemia. In acute fulminant hepatic failure, sepsis or septicemia may be masked by fever, hypoglycemia, and leukocytosis that might also represent clinical manifestations of hepatic disease.

Animals with chronic disorders of the biliary tree or with chronic hepatic neoplasia are more likely to develop intrahepatic infections. Any disorder associated with bile stasis predisposes to systemic and splanchnic endotoxemia. Risk factors associated with biliary tract infection include advanced age, recent episodes of cholangitis, acute cholecystitis, choledocholithiasis, and obstructive jaundice.

Treatments shown to reduce susceptibility to infection and liver injury include administration of N-acetylcysteine, α-tocopherol, glutamine, oral bile acids, and enteric and systemic antibiotics. These treatments increase microvascular perfusion, reduce enteric bacterial translocation, augment innate immunity, and protect against oxidant injury. While awaiting results of culture and sensitivity (tissue, abdominal effusion, bile) antibiotics against enteric opportunists should be administered empirically, avoiding drugs extensively metabolized in the liver. Combination of a β-lactamase resistant penicillin, metronidazole (7.5 mg/kg, PO, bid), and enrofloxacin (2.5–5 mg/kg, PO, IM, or IV, bid), may be beneficial during initial treatment when the underlying infectious cause remains unclear.

Mycotic Diseases

The most common mycotic infections associated with liver dysfunction are coccidioidomycosis (see Fungal Infections: Coccidioidomycosis) and histoplasmosis (see Fungal Infections: Histoplasmosis). In severely affected animals, clinical signs include ascites, jaundice, and hepatomegaly, in addition to signs associated with other involved systems. Antifungal treatment is variable, determined by the severity of infection and individual clinical response. Because liver involvement in histoplasmosis is seen with disseminated disease, aggressive chemotherapy (including combinations of either itraconazole or ketoconazole and amphotericin B) are recommended. Debilitated animals have a poor prognosis. Coccidioidomycosis can be treated successfully with longterm (6–12 mo) ketoconazole or itraconazole. However, relapses may occur.

Protozoal Diseases

Toxoplasmosis

Toxoplasmosis (see Toxoplasmosis) can cause acute hepatic failure associated with hepatic necrosis. Toxoplasma gondii is more commonly seen in cats positive for feline immunodeficiency virus and FeLV. Icterus, abdominal effusion, fever, lethargy, vomiting, and diarrhea are seen in addition to clinical signs consistent with CNS, ocular, or pulmonary involvement. Liver disease in dogs is rare but when seen is either in an immunocompromised host or in young dogs. Young dogs may be concurrently infected with canine distemper virus; in these, illness is acute in onset and rapidly fatal. Diagnosis of toxoplasmosis can be difficult; a positive IgM titer indicates active clinical disease. Clindamycin (12.5 mg/kg, PO or IM, bid for 4 wk) is the drug of choice. Because clindamycin is metabolized in the liver, dosage reduction may be necessary in severe hepatic insufficiency. Oral clindamycin should be followed by a bolus of water or food to prevent esophageal irritation. Prognosis depends on the degree of debilitation and stage of disease at initial diagnosis and the associated disorder causing immunosuppression. Despite improvement, animals should be considered chronically infected.

Leishmaniosis

Canine leishmaniosis (see Leishmaniosis) is a multisystemic disease caused by protozoan parasites of the genus Leishmania in Mediterranean countries, Portugal, the Middle East, and some parts of Africa, India, and Central and South America, occasionally in dogs in the USA (especially Foxhounds). Clinical features in dogs with naturally occurring leishmaniosis include nonregenerative anemia, increased AP, ALT, and AST activity, hypoalbuminemia, and variable bilirubin concentrations. Multifocal hepatocellular necrosis, vacuolar degeneration, and infiltration by parasitized macrophages are common. While liver lesions are interpreted to represent sequential stages of hepatic infection in visceral leishmaniasis during chronic disease, no correlation has been shown between histologic features and breed, sex, age, clinical features, or hepatic parasite load.

Treatment is rarely curative and prognosis for debilitated patients is poor. Owing to the zoonotic potential of the infection, owners must be informed that the organism will never be completely eradicated and that relapses may require repeated treatment. This is particularly important if an owner is immunocompromised. In the absence of renal insufficiency due to infection, a high protein diet is recommended. The most common specific treatment recommended in the USA is allopurinol (7.0–20.0 mg/kg, PO, bid-tid) given for 3–24 mo or indefinitely.

Last full review/revision March 2012 by Sharon A. Center, DVM, DACVIM