How I Treat Chronic Hepatitis
World Small Animal Veterinary Association World Congress Proceedings, 2010
David C. Twedt, DVM, DACVIM
Fort Collins, CO, USA

The management for chronic hepatitis (CH) begins first by removing the primary etiology if it is identified. The four major goals for therapy should then be: 1) dietary manipulation, 2) specific therapy directed at reducing inflammation, fibrosis and/or copper, 3) basic hepatic support and 4) treating secondary complications that result from liver disease.

Specific Therapy

Antiinflammatory Therapy

Decreasing inflammation is a specific therapy used in CH to reduce the amount of hepatocellular death and fibrosis. This would be especially important in suspected cases of immune mediated hepatitis. Prednisone is commonly used with a suggested initial dose of 1 to 2 mg/kg/day followed by gradual tapering of the dose.1 The only accurate way to evaluate a response to therapy is to re-biopsy the patient at some later point because it becomes impossible to determine if there is improvement based on liver enzymes when the dog is on prednisone. Azathioprine in conjunction with prednisone may also be beneficial in dogs.2 A dose of 2.2 mg/kg/day is the suggested starting dose and after one to two weeks I give it q 48 hours. I have recently been using cyclosporine alone and have observed a good clinical response. I generally prescribe 5 mg/kg bid or q 24 hrs sometimes tapering to q 48 hours. When using only cyclosporine and not prednisone it is possible to monitor the liver enzymes and adjust the therapy accordingly.

Copper Reduction

When there is significant hepatic copper accumulation >1000 µcg/g dry weight liver (normal < 400 µg/g) I prescribe a low copper diet (prescription liver diets) and copper chelation and/or zinc therapy. The copper chelators penicillamine or trientine are the standard therapies used to remove excess hepatic copper in cases of breed-associated copper hepatotoxicity. Penicillamine is my preference of a chelator. The dose for either drug is 15 mg/kg bid given on an empty stomach.3,4 I generally treat for a minimum of four months or longer with very high copper concentrations. Once adequately decoppered I switch the patients to oral zinc therapy. Zinc has anti-fibrotic and hepatoprotective properties but when given at high doses it prevents hepatic copper re-accumulation in patients that have been decoppered with chelators.5 An initial induction dose of 15 mg/kg body weight (or 50 to 100 mg BID) of elemental zinc given twice a day is suggested. Following 1 to 3 months of the induction the dose can be reduced in half.

Choleretic Drugs

Ursodeoxycholic acid (Ursodiol) is a choleretic agent that also has hepatoprotective properties including decreasing concentrations of hepatoxic bile acids, reducing hepatocellular inflammatory changes as well as some immunomodulating effects. The hepatoprotective characteristics of ursodeoxycholic make it a good adjunct therapy and I will prescribe ursodiol in all my CH cases. The dose for ursodeoxycholic acid is 15 mg/kg daily or q 48 hours.

Antifibrotic Drugs

The key in reducing or preventing fibrosis is to stop inflammation that is the signal for fibrosis production. Colchicine has been used to treat people with CH and other types of liver fibrosis. There is still no good data in humans and dogs with CH that colchicine is beneficial.6 There are but 2 case reports of colchicine in dogs both having questionable results. A dose of 0.03 mg/kg/day has been suggested. I rarely prescribe colchicine in my CH cases because of the lack of convincing evidence of effectiveness. The angiotensin II antagonist losartan is shown to decrease hepatic fibrosis in humans and may be beneficial in canine CH though there are no studies in the dog.


They are indicated for primary hepatic infections such as leptospirosis or with positive liver cultures. There also may be some merit for a short course of antibiotic therapy for suspected secondary bacterial localization due to impaired hepatic Kupffer cell function in filtering the portal blood as it enters the liver.7

Liver Support

There is considerable evidence of oxidative damage in CH and justification for using antioxidants or various nutraceuticals to provide an environment for optimal liver function. I prescribe one or several of the following antioxidants. They are all very safe and may provide additional liver support. Vitamin E (alpha-tocopherol) functions as a cellular membrane-bound antioxidant.8 Vitamin E is inexpensive and safe when supplemented at a dose of 10 IU/kg/day. S-adenosylmethionine (SAMe) has both hepatoprotective and antioxidant properties.9 Milk thistle, the extract silymarin or the active stereoisomer silibinin has been shown to inhibit lipid peroxidation, increase hepatic glutathione content and to retard hepatic collagen formation. Milk thistle is reported to have an extremely low toxicity and when the active isomer silibinin is complexed with phosphatidylcholine, intestinal absorption is increased.10

Treating Liver Complications

Common complications of advanced liver disease include ascites, GI ulceration and hepatic encephalopathy (HE). These complications indicate advanced disease and a predicted short survival time. I find that ascites secondary to liver disease and portal hypertension responds better with spironolactone than with furosemide diuretic therapy. In some cases combination diuretic therapy is required. If the patient has a very tense abdomen from the ascites I will perform paracentesis. HE is treated with diets of moderate protein content (prescription liver diets) and lactulose with the dose adjusted to cause several soft stools a day. If HE continues, intestinal antibiotics such as amoxicillin or neomycin are added. I generally treat gastrointestinal ulceration with famotidine and sucralfate.


The dietary and treatment plan should be individualized for each patient. Careful monitoring and adjustment of the treatment is predicated on the clinical response, laboratory changes or histology findings.


1.  Strombeck DR, et al. J Am Vet Med Assoc 1988; 193:1109.

2.  Murray-Lyon IM, et al. Lancet. 1973; 7; 1(7806):735.

3.  Smedley R, et al. Vet Pathol 2009; 46:484.

4.  Mandigers PJJ, et al. J Vet Intern Med 2008; 19(1):40.

5.  Rolfe DS, et al. Vet Clin N Am Small Anim Pract 1995; 25:399-417.

6.  Rambaldi A, et al. Liver 2001; 21(2):129.

7.  Vlachoginnakos J, et al. Gut 2001 49:303.

8.  Sokol RJ, et al. Pediatr Clin North Am 1996; 43:471.

9.  Center SA, et al. Am J Vet Res 2002; 63:1187.

10. Filburn CR, et al. J Vet Pharmacol Ther 2007; 30:132.


Speaker Information
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David C. Twedt, DVM, DACVIM
Fort Collins, CO, USA