Despite the many advances in veterinary medicine, there is still a huge amount that we do not know when it comes to optimally treating inflammatory liver disease. With inflammatory liver disease, the primary treatment is dependent largely on the predominant inflammatory cell type, so whether it is neutrophilic or lymphocytic inflammation. Therefore achieving an accurate diagnosis is important. We also need to consider concurrent diseases, since frequently cats have a combination of inflammatory liver, pancreatic and intestinal disease and this may also influence management. Furthermore, other concurrent diseases such as diabetes mellitus or hepatic lipidosis can also be present. Much of the management is symptomatic and supportive, dependent on predominant clinical signs.
Acute Neutrophilic Cholangitis
Antibiotic treatment is the priority for acute neutrophilic cholangitis. The choice of antibiotic should ideally be based on the results of culture of bile and sensitivity tests. However, initial selection of antibiotic must be made before results of bacteriologic culture are available, and sick patients may not be well enough for anaesthesia and sample collection before starting antibiotic treatment, or bacteriology may not be performed if surgical treatment is not a necessary part of the management. Often the diagnosis is presumptive based on other clinical features.
E. coli is the most frequently isolated organism but a mixed growth of other organisms that constitute the normal small intestinal bacterial flora are frequently found, (most commonly Enterococcus spp., Streptococcus spp., Clostridium spp. and Bacteroides spp.) reflecting ascending infection from the gut. The ideal feature of an antibiotic selected for empiric use is that it should be broad spectrum, bactericidal, achieve therapeutic levels in bile, and not require hepatic metabolism for activation or excretion. Potentiated synthetic penicillin (e.g., amoxicillin-clavulanate), cephalosporin (e.g., cephalexin), or a fluoroquinolone combined with metronidazole for additional activity against anaerobes, are frequently used with good success. Enrofloxacin should be avoided in cats due to the associated toxicity that may result in retinal degeneration. Antibiotic treatment should be maintained for at least 4 to 8 weeks to minimize the risk of recurrence.
If extrahepatic biliary duct obstruction is present, cholecystectomy may be necessary to remove inspissated bile. Cannulation of the duodenal papilla may also be required in order to lavage and ensure patency of the common bile duct. If complete biliary obstruction is identified at laparotomy, cholecystoduodenostomy may be required. A high peri- and post-operative mortality rate has been reported for cats requiring surgical intervention, although if the cat survives the immediate post-operative period then the prognosis is reasonable. The chance of a successful surgery and a good outcome are very dependent on the expertise of the surgeon and ability for intensive post-operative care, and the author has experienced very good outcomes following biliary surgery performed by experienced surgeons.
Chronic Neutrophilic Cholangitis
The dilemma in treatment of cats with cholangitis involving mixed inflammatory infiltrates is whether antibiotics or corticosteroids are most appropriate for treatment. Corticosteroids used judiciously at an anti-inflammatory dose are likely to be helpful by facilitating bile flow through reducing biliary tract inflammation, and reducing development of fibrosis. However, as bacterial infection is likely to have instigated the inflammatory changes, antibiotics are also indicated. Starting both treatments at once can make it difficult to assess response to treatment. The authors approach is to initiate antibiotic treatment whilst bacterial culture of liver tissue and bile is pending. If bacterial cultures are positive, a 4–6 week course of antibiotics is administered, but if there is not complete clinical improvement after 1–2 weeks, an anti-inflammatory dose of prednisolone (0.5–1 mg/kg daily) is also initiated. If cultures are negative, anti-inflammatory doses of prednisolone are initiated earlier, and antibiotics continued for 2–3 weeks.
Corticosteroids are the mainstay of treatment for lymphocytic cholangitis and considerable clinical experience supports their beneficial effect. Prednisolone is frequently used at an initial immunosuppressive oral dose of 1 to 2 mg/kg twice a day, which is gradually reduced over an extended period of 6 to 12 weeks according to the progress of the case. Other immunosuppressive agents are occasionally used (e.g., cyclosporine, chlorambucil), but experience of their use and value is more limited. Colchicine may be used at a dose of 0.03 mg/kg once a day in an attempt to combat fibrosis, although there have been no controlled trials to confirm any beneficial effect and it may cause gastrointestinal side effects; the author does not routinely use this. It is unusual for ascites to be so severe as to require additional treatments such as abdominocentesis and diuresis, but these may need to be occasionally considered.
Symptomatic and Supportive Treatments for Inflammatory Liver Disease
For all forms of cholangitis various combinations of other symptomatic and supportive treatments are likely to be of benefit. In acute neutrophilic cholangitis where the cats are usually quite sick patients, aggressive treatment is often required before complete investigation can be performed. Fluid therapy and nutritional support are frequently needed.
Analgesia is vital for the patients with acute neutrophilic cholangitis or those that may have concurrent pancreatitis, particularly as abdominal pain can be difficult to recognise in cats but is common with these conditions and can be the reason for presenting signs such as lethargy/malaise and inappetance. Abdominal pain can also be a trigger for vomiting. Opioid analgesia is recommended. Buprenorphine (0.01–0.02 mg/kg IM, IV, SC or sublingually every 8 hours) is usually effective. Where more potent analgesia is required, methadone, morphine, or fentanyl patches can be useful. Non-steroidal anti-inflammatory drugs should be avoided due to increased risks of renal toxicity in dehydrated or hypovolaemic patients.
Although intractable vomiting is not common in feline patients, many cats will benefit from administration of anti-emetics, since nausea is an important cause of inappetance and development of food aversion. Maropitant administered subcutaneously or orally appears to be an effective anti-emetic in cats and is usually the author's first choice now. If the cat requires intravenous fluid therapy then a constant rate infusion of metoclopramide can be administered at 1–2 mg/kg/24 hours, by adding the appropriate amount to the cat's IV fluids. This has the benefit of pro-kinetic activity also, and so may be more useful in cats that have ileus which may be particularly associated with concurrent pancreatitis. Metoclopramide appears to be quite effective administered as a CRI, but is much less effective if administered by intermittent injection or orally. In patients with intractable vomiting, ondansetron or chlorpromazine (NB can have sedative and hypotensive side-effects) can be useful.
The priority with nutritional therapy depends partly on the clinical presentation, and presence of concurrent disorders such as inflammatory bowel disease or pancreatitis. Enteral assisted feeding may be required in cats that are persistently anorexic.
For cats that are mildly inappetant, appetite stimulants can be useful. Mirtazapine is a serotonergic drug that can be quite a potent appetite stimulant in many cats and also has anti-emetic properties. Care should be taken to ensure adequate anti-emetic therapy and analgesia is being used before starting appetite stimulants, as occasionally the result of stimulating appetite whilst the cat may develop pain and/or nausea upon eating, can contribute to food aversion.
For both neutrophilic and lymphocytic cholangitis, choleretics may be of value in promoting bile flow provided that extrahepatic biliary obstruction is not present. Ursodeoxycholic acid (UDCA) at a dose of 10 to 15 mg orally, once a day is used. The potentially beneficial effects of UDCA include reducing the proportion of hydrophobic bile acids that have toxic effects on hepatocellular membranes in addition to potential anti-inflammatory, immunomodulatory and antifibrotic properties. These effects have been demonstrated in vitro and these properties make it potentially useful in all forms of inflammatory liver disease. However, no controlled clinical trials have been reported to demonstrate a beneficial effect of UDCA, but it is widely used and appears to be safe.
Vitamin K supplementation is indicated if defects in clotting function are identified, or can be used empirically, particularly prior to any biopsy or surgical procedure.
A range of preparations of S-adenosyl-L-methionine (SAMe) supplements are also available and may be beneficial in restoration of glutathione levels and reducing oxidative damage, and also in increasing levels of cysteine and taurine, which are required for bile acid conjugation and a cytoprotective effect. However, relative amounts of different isomers of SAMe, stability and bioavailability is crucial if it is to be of any potential benefit, and this may significantly vary between products.