Written by Dr. Alice Crook and taken from the Canine Inherited Disorders Database with permission
related terms: chronic liver disease, copper-associated hepatitis/copper toxicosis in Bedlington Terriers, chronic active hepatitis, Doberman hepatopathy, chronic inflammatory hepatic disease
Chronic hepatitis is a catch-all diagnosis for a number of diseases where there is inflammation and death of liver tissue. Affected dogs develop a slowly progressive liver disease. There are many possible causes including viruses, bacterial infection, and some drugs. A familial predisposition to the development of chronic hepatitis exists in some breeds, although the cause is unclear. These breeds are listed below.
In Bedlington Terriers and West Highland White Terriers, an inherited defect in the metabolism of copper is known to cause chronic hepatitis (copper-associated hepatitis/copper toxicosis in Bedlington terriers). It is estimated that 25% of Bedlington Terriers have the disorder, and 50% are carriers (i.e.. they will not become ill, but can transmit the disorder to their offspring). Copper accumulation occurs in some other breeds as well, but whether the excess in copper is the cause or the result of liver disease is unknown.
Inheritance in the Bedlington Terrier is autosomal recessive. The mode of inheritance is unknown in other breeds.
Doberman Pinscher (predominantly female dogs affected), American and English Cocker Spaniel, Skye Terrier, Labrador Retriever.
Copper-associated hepatitis – Bedlington Terrier and West Highland White Terrier
For many breeds and many disorders, the studies to determine the mode of inheritance or the frequency in the breed have not been carried out, or are inconclusive. We have listed breeds for which there is a consensus among those investigating in this field and among veterinary practitioners, that the condition is significant in this breed.
The liver has a large reserve capacity, meaning there must be damage to a significant portion before you will see any signs of illness in your dog. The first signs of liver disease are generally vague and non-specific, and include loss of appetite, vomiting, weight loss, depression, lethargy, and/or increased drinking and urination. As the disease becomes advanced, there will be signs more specific to liver failure such as jaundice (you may see yellowing of your dog’s eyes for example), coagulation problems, fluid accumulation (ascites), extreme weight loss, and neurologic abnormalities (hepatic encephalopathy) such as head pressing or behavioral changes, due to the build-up of toxins normally metabolized by the liver.
In affected Bedlington Terriers, there is progressive accumulation of copper in the liver over time. Associated liver disease may manifest itself in 3 ways.
1) Young dogs (less than 6 years of age) may suddenly develop signs of liver failure, including vomiting, depression and lethargy. Most will die within a few days despite intensive therapy. Others will recover over a few weeks, and thereafter experience occasional milder bouts that may be associated with stressful events such as showing or traveling.
2) In middle-aged to older dogs, similar but less severe signs develop insidiously and the disease has a more chronic course. Gradual weight loss and deterioration in condition are common initially, while specific signs of liver disease (as listed above) develop in the advanced stages of the disease.
3) Young as yet clinically unaffected dogs may be found to have elevated liver copper and biochemical/pathological changes associated with liver disease. These are the dogs in whom treatment will be most effective.
West Highland white terriers are also affected by a disorder of copper accumulation, but the magnitude of increase is less. Diagnosis, signs of illness, and principles of treatment are similar to the Bedlington Terrier.
Before liver disease reaches an advanced stage, the clinical signs are generally vague and non-specific. Your veterinarian will do some routine diagnostic blood tests which will show elevations in liver enzymes. This is investigated further with specific liver function tests. Once the problem has been pin-pointed to the liver, your veterinarian will take a liver biopsy which will be sent to a veterinary pathologist. This is necessary to differentiate chronic hepatitis from other causes of liver disease (such as liver cancer or an infection), and to determine the severity and extent of the problem.
For the veterinarian: Elevated ALT is the most consistent biochemical abnormality. With acute onset hepatic necrosis there may be hepatomegaly. With chronic advanced disease, the liver is small and not palpable due to fibrosis and cirrhosis.
Liver biopsy is required for definitive diagnosis of chronic hepatitis, to characterize the extent of fibrosis and progression to cirrhosis (which is by definition irreversible and indicative of a poor long-term prognosis), and also to quantify hepatic copper levels. The key histopathologic feature is moderate to severe inflammation. The role of hepatic copper accumulation is controversial. Copper is commonly elevated, but this is believed by most to be secondary to the chronic inflammation, in contrast to the primary copper accumulation that causes copper-associated hepatitis in Bedlington and West Highland white terriers.
Copper-associated hepatitis should be suspected in any Bedlington terrier with physical or biochemical evidence of liver disease, and biochemical screening should be done in any Bedlington terrier with a vague illness. Asymptomatic affected dogs can be detected through biochemical screening (2/3 will have elevated ALT), liver biopsy, or a radioisotope study using copper-64. Affected dogs will have reduced stool radioactivity compared with normal dogs, due to reduced biliary excretion of copper. A genetic marker has been identified for copper toxicosis in Bedlington Terriers that will detect affected and carrier dogs at any age – see www.vetgen.com
Unfortunately, liver damage is often advanced by the time the disease is recognized. Depending on the stage of your dog’s illness when it is diagnosed, treatment may involve intravenous fluids, antibiotics, corticosteroids, dietary management, and possibly medication to reduce copper levels in the liver. Your veterinarian will discuss with you the prognosis for your dog.
In Bedlington Terriers, there are a few different drugs to control copper accumulation in the liver. These must be given for the life of the dog to prevent further build-up of copper. If the disorder is detected early, when there are no or few clinical signs, these drugs will allow many dogs to live out a normal life.
For the veterinarian: In Bedlington Terriers, D-penicillamine (copper chelator which promotes urinary copper excretion), trientine hydrochloride (an alternative copper chelator) or zinc therapy (decreases intestinal copper absorption) may be used to gradually reduce hepatic copper content and prevent further accumulation. Treatment is similar in the West Highland White Terrier. Because copper accumulation is not continuous throughout life in the Westie, mature dogs may not require chelation therapy, depending upon hepatic copper levels.
Unfortunately, hepatic liver damage is generally advanced by the time a liver biopsy is taken and the disease is recognized, leading to a poor prognosis. Improvement may occur with prednisone therapy. The usefulness of copper chelation therapy in breeds other than the Bedlington and West Highland White Terrier remains unclear.
A genetic marker has been identified for copper toxicosis in Bedlington Terriers that will detect affected and carrier dogs at any age – (see www.vetgen.com) Because of the prevalence of this serious disorder in the Bedlington Terrier, all dogs to be used for breeding should be tested. The results may be registered with the Orthopedic Foundation for Animals (see www.offa.org) Testing may also be done by liver biopsy but dogs must be older than 1 year of age so that sufficient copper accumulation will have occurred to be detectable.
There is no similar testing available for other breeds. Affected dogs should not be bred, and breeding of their parents should be avoided as well.
FOR MORE INFORMATION ABOUT THIS DISORDER, PLEASE SEE YOUR VETERINARIAN.
Johnson, SE.1995. Diseases of the liver. In S.J. Ettinger and E.C. Feldman (eds.) Textbook of Veterinary Internal Medicine, pp. 1313-1357. W.B. Saunders Co., Toronto.
Leveille-Webster, C.R. and Center, S.A. 1995. Chronic hepatitis: therapeutic considerations. In J.D. Bonaguara and R.W. Kirk (eds.) Kirk’s Current Veterinary Therapy XII Small Animal Practice. pp. 749-756. W.B. Saunders Co., Toronto.
Twedt, D.C. 1997. Treatment of chronic hepatitis. ACVIM- Proceedings of the 15th Annual Vet. Med. Forum, pp.234-236.
Leveille-Webster, C.R. 1996. Medical management of inflammatory hepatic disease in dogs. ACVIM-Proceedings of the 14th Annual Vet. Med. Forum, pp. 43-44.
Orthopedic Foundation for Animals, Registry for Copper Toxicosis in Bedlington Terriers, www.offa.org