Pharmacological management of canine and feline liver disease (Proceedings)
Rational pharmacological management of canine and feline liver diseases is built around removal of the inciting cause, specific therapy (e.g. anti-inflammatory, antifibrotic or anticopper agents) and provision of general liver support1. Generally speaking, treatment recommendations are based upon the suspected pathophysiology of the disease or extrapolated from the human medical literature and are not based on veterinary clinical trials2.
Anti-inflammatory agents are indicated in the treatment of liver diseases characterized by histological evidence of mononuclear (lymphocytes and plasma cells) inflammation for which no infectious etiology is suspected2. Corticosteroid therapy is generally used for canine chronic hepatitis, feline lymphocytic cholangitis and occasionally feline mixed cholangitis on the assumption that these conditions have an immune-mediated etiology and that control of inflammation is in and of itself beneficial and may delay or prevent fibrosis. In a single retrospective study of 151 dogs with chronic hepatitis, dogs treated with corticosteroids had longer survival compared to untreated dogs1,2. Recently the WSAVA Liver Standardization Group concluded that in the treatment of canine chronic idiopathic hepatitis it is "unethical" not to use glucocorticoids but the group acknowledged that "the supporting evidence is weak"2. Glucocorticoid regimens for canine chronic hepatitis have not been critically evaluated, but treatment recommendations include prednisolone (2.2 mg/kg/day)4 or prednisone (1-2 mg/kg/day)1,5. The response to treatment is ideally monitored via serial liver biopsies and glucocorticoid therapy continued until inflammation and hepatocellular death are resolved histologically5. As this may not be acceptable to owners, glucocorticoids may be tapered to 0.5 mg/kg/day after 6 weeks of treatment or based upon improved clinical signs and liver enzyme activities. Improvement in hepatocellular leakage enzyme activities (i.e. ALT) is expected if the disease process is controlled4. Anecdotally, azathioprine (2 mg/kg q48 hours) or cyclosporine (3-5 mg/kg/day in divided doses) have been used as alternative or adjunctive immunosuppressive agents where glucocorticoids are ineffective or the side effects intolerable4. For treatment of feline lymphocytic cholangitis, prednisolone at an initial dose of 1-2 mg/kg q12 hours and tapered over 6-12 weeks (assuming continued clinical improvement) has been recommended3.Cholchicine
Fibrosis is a potential sequlae of chronic hepatic inflammation2. Inflammatory processes disrupt hepatocellular membranes resulting in the release of mediators such as TNF-alpha which attracts hepatic stellate cells, the major cell type responsible for hepatic fibrosis4. Excessive fibrosis limits the ability of vessels to distend, increases resistance to blood flow, impairs hepatocyte function and causes permanent hepatic distortion and dysfunction4. Prevention of fibrosis is an important treatment goal and is best achieved through controlling inflammation, limiting oxidative damage and, in some cases, administration of specific anti-fibrotic agents. Cholchicine is though to inhibit collagen formation by reversibly inhibiting microtubule assembly. The efficacy of cholchicine as an anti-fibrotic is questionable and veterinary data regarding its anti-fibrotic properties are limited to individual case reports. The recommended canine dose of cholchicine is 0.014-0.03 mg/kg q24 hours6. Its use in the cat has not been described. Gastrointestinal (anorexia, vomiting, diarrhea) side effects are possible. Colchicine administration has also been associated with development of bone marrow necrosis and as such should not be combined with other potentially myelosuppressive agents such as azathioprine, chemotherapeutics, fenbendazole, chloramphenicol or phenylbutazone7. Colchicine is only indicated in canine patients with biopsy confirmed hepatic fibrosis, however given the lack of data on its efficacy and potential for side effects, its use can not be routinely recommended.