Feline inflammatory liver disease - an overview (part 2)
Treatment of Lymphocytic Cholangitis
Treatment is largely empirical, as it is important to remember that there are NO specific treatments for liver disease. Supportive therapies for hepatic disease may be beneficial (see Table 4).
• Prednisolone (1-2 mg/kg q 12h per os). Due to the suspected immune-mediated etiology, immunosuppression is considered appropriate. Once remission of clinical signs is achieved, the dose should be tapered over 6-12 weeks to 1 mg/kg q 48h) and maintained on every other day if needed.
• Other immunosuppressive agents may be considered e.g. methotrexate (0.13 mg/cat per os q 8-12h for 3 doses; given every 7-10 days), chlorambucil (2-5 mg/m2 per os up to once every 48h or 2-4 mg per os every 1-3 weeks), or cyclosporin A (measure serum levels, start at 2mg/kg per os q 12h). Note that these drugs are all potentially hepatotoxic. Do not give azathioprine; it is toxic to cats.
Limited studies are available on the outcome of cats with LC, but the authors’ clinical experience is that cats with this condition generally respond well to treatment. Cats with ascites carry a poorer prognosis than those presenting with jaundice alone, as ascites may represent more marked fibrosis due to more advanced disease. Although clinical signs may resolve, owners should be warned of the potential for relapse, and some cats may require chronic therapy with prednisolone to prevent relapses when medication is stopped.
Previously termed suppurative or exudative cholangitis/cholangiohepatitis, both acute (ANC) and chronic (CNC) forms are described. Neutrophilic cholangitis is attributed to ascending bacterial infection from the gastrointestinal tract. Infection may also ascend up the pancreatic bile duct, hence the frequent association with NC and pancreatitis. Inflammatory bowel disease (IBD) is also frequently associated with these conditions, resulting in the term “triaditis”. Recently Helicobacter infection has been suggested to play a role in development of NC (4).
Cats of any age may be affected, but middle-aged to older cats are reported to be affected more typically. With ANC clinical signs are typically severe, and include fever, anorexia, vomiting and lethargy. Vomiting is frequent in all types of biliary disease, possibly because inflammation of the bile ducts stimulates their rich autonomic nerve supply and triggers the emetic center of the brain. Cats with ANC may be jaundiced and/or demonstrate abdominal pain. Acute disease may progress to chronic disease. CNC typically has a waxing and waning time course of months to years, with periods of anorexia, vomiting and weight loss. Cats with CNC may be jaundiced and show hepatomegaly; ascites is rare.
Systemic signs may be associated with secondary infections, typically of the liver and/or pancreas and “triaditis” is common: in one study 83% of cases had concurrent IBD whilst 50% had pancreatitis (5).
Initially with ANC, when the inflammation is limited to the larger bile ducts and gallbladder, there may be little or no changes in the total bilirubin and even the liver enzymes. More typically, there are mild to moderate increases in ALT, ALP, GGT, bile acids and bilirubin. Most CNC cases have raised liver enzymes (with GGT typically being proportionately higher than ALP). Hematology may reveal a mild to moderate leukocytosis, typically due to neutrophilia. Chronic or severe disease may result in mild anemia, lymphopenia or lymphocytosis, monocytosis, and/or thrombocytopenia. Prolonged clotting times may also be identified. Radiographs are often unhelpful, with ultrasound examination being the imaging modality of choice. The liver typically appears heterogeneous with increased echogenicity. The bile ducts are typically distended (> 5 mm) and often tortuous in appearance. The gallbladder may appear distended, with a thickened wall (> 1 mm) which suggests cholecystitis. Cholelithiasis (gallstones) may occasionally develop. Associated findings may include enlarged mesenteric lymph nodes, pancreatic irregularity, and/or thickening of the duodenal walls. Ultrasound guidance may also be used to obtain an aspirate of bile from the gallbladder (taken through the right medial liver lobe where the gallbladder is attached to the liver to reduce the risk of intra-peritoneal leakage of bile). This procedure carries the risk of bile peritonitis, particularly if cholecystitis is present or a large bore needle is required for centesis due to the inspissated nature of the bile. Aspirates from both the liver and bile should ideally be sent for cytological assessment and bacterial culture (preferably aerobic and anaerobic culture). Liver biopsies are more reliable for assessment of hepatic architecture.
Primary differential diagnoses to consider for acute disease include pancreatitis, sepsis, systemic infections (e.g. Salmonella, FIP, toxoplasmosis), HL, hepatotoxicity or biliary tract obstruction.
Due to the association with infection, antibacterials are administered, along with supportive therapies (Table 4). Antibacterials may need to be given for 1-3 months. E. coli is the most frequently isolated organism, but mixed infections are not uncommon. Ideally, antibacterials should be administered as directed by culture and sensitivity of bile and/or liver samples, but empiric choices are as follows:
• Amoxicillin/clavulanate (11-22 mg/kg per os q 8-12h) or
• Cephalexin (10-35 mg/kg per os q 8-12h) plus a fluoroquinolone (well concentrated in bile). The authors prefer marbofloxacin (2 mg/kg per os q 24h) over enrofloxacin because of the risk of irreversible blindness in cats plus
• Metronidazole for its effect against anaerobes and its immune-modulating effects (7.5-10 mg/kg per os q 12h). Do not use higher doses, as these can be hepatotoxic, neurotoxic and potentially teratogenic.
• Clindamycin (5.5 mg/kg per os q 12h) has efficacy against anaerobes and gram positive organisms, but not gram negative organisms. It is concentrated in the bile, but care should be taken with hepatic impairment, as this is the main route of metabolism.
• In very severe cases give according to ‘4 quadrant cover’ IV (i.e. to cover gram positive and negative, anaerobes and aerobes – e.g. amoxicillin/clavulanate + fluoroquinolone + clindamycin or metronidazole).
Supportive therapies may be required for management of pancreatitis (e.g. intravenous fluid therapy, analgesia, antibiotics) and if IBD is present, concurrent therapy with prednisolone may also be required.
Prognosis may depend in part on the severity of the disease at presentation and any concurrent problems. The majority of cats are reported to survive in excess of 1 year, with 1 study reporting a median survival time of 29 months (6).
Some cases of disease are difficult to categorize, due to the mixed nature of the inflammatory disease. This is especially true in more chronic cases. Unless infection can be ruled out by negative culture of bile and hepatic tissue, it is wise to initiate antibacterial therapy in these cases, accepting that prednisolone may also be required if the response to antibacterials alone is not adequate.
Chronic cholangitis associated with liver flukes
This condition is reported in association with a number of species of the Opisthorchiidae family which require both snails and fish as intermediate hosts. Endemic areas for fluke species include the Americas, India, China, Japan and Northern Europe. Cats acquire the infection by eating raw fish, with the immature flukes migrating from the intestine to the liver via the bile ducts. Low grade infections may be asymptomatic, but heavy burdens may cause anorexia, vomiting, weight loss, abdominal pain, lethargy and icterus. A peripheral eosinophilia may be present, but elevations in liver enzymes may be transient. Diagnosis requires demonstration of the adult flukes or operculated eggs on liver biopsy samples or aspirated bile. Treatment comprises praziquantel (30 mg/kg per os q 24h for 5-10 days), but surgical cannulation and drainage of bile may be required for more severe cases.
Other causes of inflammatory liver disease
FIP may be associated with elevated liver enzymes and bilirubin due to pyogranuloma formation and hepatic necrosis. Usually other clinical signs will be present to suggest a systemic disease process, but differentiation of LC with ascites may require biopsy. Toxoplasmosis may be associated with elevated liver enzymes, and less commonly, icterus. Diagnosis is usually based on elevated IgM antibody titers.
Drug reactions may induce hepatic damage either through toxicity or idiosyncratic reactions. The most commonly recognized drugs causing toxicity include diazepam, methimazole and carbimazole, potentiated sulphonamides, tetracyclines, phenobarbitone, griseofulvin (especially FIV+ve cats) and paracetamol (acetaminophen).
Nutrition in cholangitis cases
Whilst some cats with cholangitis may continue to eat well, or if inappetant may respond to tempting, hand feeding or syringe feeding, many cats may require placement of feeding tubes. In the first instance, naso-esophageal tubes are preferred, as they are easy to place and do not require anesthesia (Figure 2). In addition, the risk of hemorrhage is minimal. However, the narrow diameter of the feeding tube limits the type of diet that can be administered via the tube, and irritation of the nasal passages may develop with prolonged use. Assuming the cat can tolerate a general anesthetic, an esophagostomy tube (Figure 3) is easy to place and allows for more prolonged feeding, potentially in the home environment. If the underlying disease merits it, a gastrostomy tube may be placed, although this is a more complicated technique requiring a more prolonged anesthetic. The cat’s individual caloric requirement should be calculated so an appropriate feeding plan can be generated (see Table 5).
Inflammatory feline liver disease is a relatively common problem in general practice. Accurate diagnosis requires examination of biopsy material obtained from the liver, ideally by histopathology. With appropriate supportive treatment, the prognosis for these conditions is generally favorable, although recurrence is possible and an owner should always be informed of this.
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