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.
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.