HEPATIC INFECTIONS

• 1. What infectious agents are associated with hepatic disease in cats?

  Infectious causes of hepatic disease include viruses (feline infectious peritonitis, feline leukemia virus), parasites (Toxocara cati, Platynosomum concinnum, Toxoplama gondii, Cytauxzoon felis), bacteria (suppurative cholangitis/cholangiohepatitis complex), and fungi (Mucor spp., Aspergillus spp).

• 2. What is the most common hepatic infection?

  The bacterial cholangitis/cholangiohepatitis complex is most common (see Chapter 29).

• 3. Which protozoans are associated with hepatic infections?

  At least four different protozoal organisms have been associated with hepatic infections: Toxoplasma gondii; a coccidia-like organism from the protozoan family Eimeriidae; a protozoan parasite similar to Hepatozoon canis; and Cytauxzoon felis (see Chapter 75). T. gondii is the most frequently encountered protozoan parasite causing cholangitis/cholangiohepatitis.

• 4. How does hyperbilirubinemia due to toxoplasmosis develop?

  Cats are infected by T. gondii by ingestion of sporulated oocysts or tissue cysts or transplacentally or lactationally from primary infection of the queen. Clinical toxoplasmosis is most severe in transplacentally infected or neonatally infected kittens; the type and severity of clinical illness depend on the degree and localization of tissue injury. The organism infects the gastrointestinal epithelium and disseminates through the blood. Intracellular replication of T. gondii tachyzoites results in destruction of infected cells and necrosis. Replication is common in hepatocytes and the pancreas and can result in hyperbilirubinemia from either hepatic disease or pancreatic disease. Hepatic disease seems to be uncommon in chronically infected cats. Clinical signs in acutely infected cats include anorexia, depression, fever, abdominal distension, crying, dyspnea, central nervous system signs, icterus, and death.

• 5. How is hepatic toxoplasmosis diagnosed?

  A diagnosis of T. gondii infection can be made by various testing procedures. Tachyzoites may be detected cytologically in various tissues and body fluids (pleural and peritoneal effusions) during acute infection. Fecal examination for T. gondii oocysts may be beneficial 1–2 weeks after initial exposure. Serologic testing has become the most practical and accepted means of diagnosing T. gondii infection. Serologic evidence of recent or active infection consists of high IgM titers, or a fourfold or greater increase in IgG titers. However, these findings document only recent infection, not clinical disease due to infection.

• 6. How is hepatic toxoplasmosis treated?

  Drugs attempted for the treatment of acute extraintestinal toxoplasmosis include clindamycin (10–12.5 mg/kg orally every 8–12 hr), pyrimethamine (0.25–0.5 mg/kg orally every 12 hr), and trimethoprim-sulfonamide (15 mg/kg orally every 12 hr). If pyrimethamine is used, it is generally combined with one of the other drugs; it is rarely given to cats because of the high incidence of side effects.

• 7. How does Cytauxzoon felis cause hyperbilirubinemia?

  Cytauxzoon felis results in severe disease in most infected domestic cats (see Chapter 75). Hyperbilirubinemia in infected cats is probably due to two mechanisms: (1) red blood cell destruction from the piroplasm stage and (2) hepatic dysfunction or cholestasis from hepatic infiltration by schizont-infected macrophages.

• 8. What trematode parasites cause hyperbilirubinemia in cats?

  The liver fluke, Platynosomum concinnum, has been reported to infect cats in tropical to semitropical climates. Infestation with this trematode is uncommon but has been reported in cats living in or with a history of travel to Hawaii, Florida, Polynesia, Malaysia, New Guinea, Australia, Nigeria, Brazil, Bahamas, and Puerto Rico. Other species of trematodes that have been identified in the livers of cats include Amphimerus pseudoflineus, Opisthorcus tenuicollis, and Metorchus conjunctus; infestation with these species is rare.

  Platynosomum concinnum requires two intermediate hosts to complete its life cycle: a land snail and a reptile (gecko, lizard, or skink) or amphibian (toad). Embryonated eggs are ingested by the land snail and hatch within the snail's intestinal tract. The miracidia then penetrate the host's tissues and transform into sporocysts. The second intermediate host ingests oocysts shed by the snail, and the cat becomes infected when it ingests an infected second intermediate host. Infective flukes migrate up the common bile duct into the gallbladder and bile ducts.

  Although most cats are subclinically infected, some cats with a high, chronic fluke burden may manifest weight loss, vomiting, diarrhea, icterus, and hepatomegaly (“lizard poisoning”). The presence of the flukes within the biliary system incites an inflammatory process that eventually may lead to bile duct fibrosis and biliary epithelial hyperplasia.

• 9. How are liver fluke infections diagnosed?

  Diagnosis of P. concinnum can be difficult because most cats are subclinically infected. Identification of the parasite by fecal examination has poor sensitivity because of the small number and variable morphology of P. concinnum eggs. Observe for the double-operculated eggs after fecal sedimentation. Cholecystocentesis is a more definitive means of diagnosing P. concinnum infection in cats; however, given the invasive nature of the procedure, it should be reserved for cases in which the index of suspicion for fluke infestation is high and the cat is clinically symptomatic.

• 10. How are liver fluke infections treated?

  Effective treatment of P. concinnum infection remains poorly defined. Current recommendations are to administer albendazole (50 mg/kg/day) until fluke eggs disappear from feces or fenbendazole (50 mg/kg orally every 12 hr) for 5 consecutive days. Albendazole may cause bone marrow toxicity in cats treated for more than 5 consecutive days; therefore, the risk-benefit ratio must be considered with chronic administration of albendazole.

• 11. Is toxocariasis a common cause of liver disease in cats?

  Toxocara cati migrates through the liver of cats after ingestion of larvated eggs or infected transport hosts (see Chapter 19). However, clinical findings consistent with liver disease are usually not detected.

• 12. What are the clinical findings of liver disease due to feline infectious peritonitis?

  Feline infectious peritonitis (FIP) is thought to result from infection by a mutated variant of the universally prevalent feline enteric coronavirus (FECV). FIP can manifest as either effusive (wet) or noneffusive (dry), depending on predominant type (humoral or cell-mediated) and efficacy of the host's immune response (see Chapter 38). Hyperbilirubinemia has been associated most commonly with the noneffusive form of FIP. A primary mechanism for hyperbilirubinemia due to FIP is the formation of perivascular pyogranulomas within the hepatic parenchyma and bile duct system severe enough to cause either synthetic liver failure, intrahepatic biliary obstruction, or extrahepatic biliary obstruction. In addition, the hyperbilirubinemia associated with FIP can result from hepatic lipidosis induced by anorexia. The definitive diagnosis of hepatic involvement with the FIP virus requires a liver biopsy to document the characteristic lesions and to perform immunohistochemistry. Classical lesions include perivascular infiltration (arterioles and venules) of proliferating macrophages, lymphocytes, plasma cells, and neutrophils. Treatment responses are variable and prognosis is guarded.

• 13. How does feline leukemia virus infection result in hyperbilirubinemia?
  Feline leukemia virus (FeLV) is the other principal viral cause of hepatic disease in cats. Although FeLV infection may cause multisystemic illness, the mechanism for liver disease usually is not associated with synthetic liver failure but rather with FeLV-induced malignant cell transformation leading to the development of hepatic lymphosarcoma. Hepatic lymphosarcoma causes hyperbilirubinemia as a result of malignant lymphocyte invasion into the hepatic parenchyma with subsequent intrahepatic cholestasis (see Chapters 24 and 31). Other mechanisms for FeLV associated hyperbilirubinemia include:

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    Direct viral induction of hemolytic anemia and subsequent hyperbilirubinemia (see Chapter 76).
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    Induction of immunosuppression and subsequent predisposition to H. felis-associated hemolytic anemia (see Chapter 75), FIP, or toxoplasmosis.
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    Induction of anorexia and subsequent hepatic lipidosis
• 14. What are the clinical findings of liver disease associated with fungal infection?

  Cats with systemic fungal disease are occasionally presented for evaluation of clinical findings consistent with hepatic disease. Anorexia, wasting, lethargy, diarrhea, and icterus are the most common clinical manifestations. In one report, Mucor spp. and Aspergillus spp. were the two reported isolates. A presumptive diagnosis is based on cytologic or histopathologic evidence of fungal infection; definitive diagnosis is based on culture. In the one large case series, all cats were diagnosed on necropsy; therefore, definitive treatment recommendations cannot be made.