Genetic Welfare Problems of Companion Animals

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West Highland White Terrier West Highland White Terrier

Chronic Hepatopathy

Related terms: hepatitis; chronic hepatitis; cirrhosis; copper storage hepatopathy; copper storage hepatitis; copper hepatotoxicosis; copper toxicosis; copper storage liver disease; copper-associated hepatitis; copper-associated hepatopathy; copper-associated liver disease; familial chronic hepatitis.

Outline: Chronic hepatopathy in West Highland white terriers is often caused by the accumulation of toxic levels of copper in the liver. The copper accumulation is probably caused by a genetic abnormality. The disease leads, after years, to liver failure. Some dogs, however, develop liver failure without toxic levels of copper. Liver failure, which causes severe malaise, can be acute, leading to death within days, or chronic (persistent and long lasting). There are no genetic tests to detect carriers so as to guide breeding strategies to control this condition.


Summary of Information

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1. Brief description

West Highland white terriers (WHWT) are prone to develop chronic liver disease (hepatopathy). The cause is unclear. Many WHWTs have a familial trait that causes accumulation of higher-than-normal levels of copper in the liver. In some cases the liver disease can be ascribed to this. However, in most WHWTs with chronic hepatopathy, the copper levels in the liver are not so high as to be expected to cause disease, so why these individuals have hepatopathy is unclear. Ultimately, whichever form of the condition is involved (with or without high liver copper levels), affected dogs develop liver failure - loss of liver function as a result of scarring (cirrhosis) -which ends with death.

Clinical signs can vary widely and usually start with vague, non-specific changes such as depression, weight loss, vomiting, deterioration of general condition, polydipsia (increased frequency of drinking) and polyuria (increasing frequency of urination), with or without jaundice (in this case due to liver failure) and ascites (fluid build-up in the abdomen that gives the affected animal a swollen-bellied appearance) (Johnson 1995, Sevelius & Jönsson 1996, Rutgers & Rishniw 2005). The prognosis (outlook) for this disease once these signs are advanced is poor but when the disease is detected earlier on it is better. The extent of permanent liver scarring, fibrosis and cirrhosis is crucial and this can be determined by microscopic examination of liver biopsies (Johnson 2000). If the liver is so scarred that little normal functioning tissue remains, the outlook is very poor.

2. Intensity of welfare impact

The welfare problems caused by chronic hepatitis in West Highland white terriers are very variable, ranging from mild in the early stages of the disease to severe in the later stages. In acute cases, affected dogs feel extremely ill, with possible nausea and generalised weakness. The welfare of chronically ill animals may be affected for months or years until death. Chronic hepatopathy significantly reduces life expectancy in untreated, and some treated, individuals.

3. Duration of welfare impact

The duration of the effects depend on the form of the disease. Some animals may die within days, others in weeks to months.

4. Number of animals affected

West Highland White terriers are known to be predisposed to chronic hepatitis (Andersson & Sevelius 1991, Thornburg et al 1986, Thornburg et al 1996) but we are unaware of data on the proportion of individuals affected.

5. Diagnosis

Because of the known breed predisposition, any West Highland white terrier with suggestive signs may be suspected of having chronic hepatopathy. However, similar signs can occur in other conditions and confirmation depends on a full examination with blood and urine tests, and often involving X-rays and ultrasound of the liver. These tests also help determine the stage of the disease and degree of liver damage and failure. Definitive diagnosis is made by biopsy of the liver and examination of the tissue under the microscope, using specific staining techniques to reveal copper accumulation. Measurement of the tissue concentration of the copper that has accumulated is also useful in this breed (Johnson 2000).

6. Genetics

The breed predisposition to this disease strongly suggests that the cause of chronic hepatopathy has a significant genetic component in the WHWT (Andersson & Sevelius 1991, Thornburg et al 1986, Thornburg et al 1996). It is also known that copper tends to accumulate in the livers of dogs of certain WHWT families, which is further evidence that the condition has a genetic basis (Thornburg et al 1996). However, as far as we are aware there have been no investigations into the genes involved and the type of inheritance has not been determined (Johnson 2000).

7. How do you know if an animal is a carrier or likely to become affected?

It is not possible to predict which animals may develop the disease. However, if relatives have been affected by chronic hepatopathy the chance of an individual being affected is higher (Thornburg et al 1996). It is not known if carriers exist – that is, if some animals may be able to pass on the disease to their offspring without ever developing the disease themselves.

8. Methods and prospects for elimination of the problem

It is currently unclear if chronic hepatopathy in WHWTs is a single disease with a single cause. Nor is it clear how the known familial tendency to accumulate copper in the liver is associated with development of the disease (but see below). The genetic basis and mode of inheritance of these conditions is also unknown and so it is difficult to devise breeding strategies to eliminate them. In such a situation, animals affected by the disease should not be used for breeding (they are often beyond breeding age or too ill to be used for breeding anyway). Because of the suspected genetic basis of the disease, it is probably sensible also to avoid breeding from any animals with a close relative that have been affected.


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1. Clinical and pathological effects

Chronic hepatitis in West Highland white terriers (WHWT) is sometimes associated with the accumulation of abnormally high concentrations of copper in liver tissue. This leads to cell damage and chronic inflammation (hepatitis). However, in the majority of cases there is no evidence of excessive copper in the liver and it seems that the liver disease may have a different basis in these WHTSs – but the cause in these cases is unknown. In both forms of liver disease (those with and without high liver copper levels), scarring (cirrhosis) and loss of liver function lead, in due course, to death.

The liver has many important functions including metabolism of macro and micronutrients, detoxifying substances in the blood, producing bile (which runs into the gastrointestinal tract), and producing blood proteins including those involved in clotting. The liver is also the major site for the control of copper levels in the body.

Copper is a mineral micronutrient that is needed, but only in very small amounts. It is used as a co-factor in many enzymes eg superoxide dismutase 1, cytochrome oxidase C, and ceruloplasmin. These enzymes are found throughout the body and their functions include altering neuropeptides (chemicals in the nervous system including the brain), producing cellular energy, detoxifying oxygen-derived radicals, mobilizing iron, helping coagulate blood and producing normal connective tissue (Rutgers & Rishniw 2005).

Dietary copper is absorbed by the gut, passes into the hepatic portal vein and is transported directly to the liver. Hepatic acinar cells in the liver take up most of it. These cells regulate the amounts in the body, either by attaching the copper to molecules that can transport it around the body in the blood stream or by excreting any excess via the bile duct into the gut.

Specialised organelles of the hepatic acinar cells, the secretory lysosomes, are involved in this excretory process. Lysosomes function to take up various waste products and toxins, including copper, and to then release them outside the cell into the biliary ducts (a network of tubes which ultimately connect to the gall bladder and the gut at the duodenum). The gene COMMD1 (previously known as MURR1) is involved in controlling this excretory lysosomal pathway (Rutgers & Rishniw 2005).

There are three possible causes of accumulation of excessive amounts of copper in the body: excessive absorption in the gut, dysfunction of its metabolism, or dysfunction of its excretion. The form that occurs in West Highland white terriers is uncertain but there can be a damaging build up of copper in the liver cells (Ludwig et al 1980). The concentration does not to continue to increase throughout the dog’s life but usually stops at a level that is higher than normal but which is not high enough to cause disease (Johnson 2000). There is evidence that copper accumulation in WHWT liver may, at least sometimes, be secondary to liver failure with an unknown cause (Andersson & Sevelius 1991).

Excessive copper concentrations lead to oxidative stress within the liver cells due to an increased concentration of free radicals. These free radicals are very reactive molecules produced as a by-product of metabolism and which cause cellular damage, and if unregulated, induce chronic hepatitis (Center 1996, Centre 1999, Spee et al 2006).

The liver can repair itself to some degree and can continue to perform its functions even when significantly damaged. However, over time, the damage and scarring caused by this disease increases until the liver can no longer function adequately. The clinical signs of copper storage hepatopathy in West Highland white terriers are due to liver damage and failure.

Dogs with copper storage hepatopathy usually have copper concentrations greater than 2000 micrograms per gram (ug/g) of liver tissue (Thornburg et al 1996), which compares to a normal liver copper level in dogs of less than 400 ug/g (Rolfe & Twedt 1995). In such dogs, areas of liver with these high levels are seen to be inflamed when samples are examined under a microscope. Many WHWTs have a familial trait that causes accumulation of higher than normal levels of copper in the liver but not to the extent at which inflammation occurs. Often these WHWTs have levels in the 200-1500 ug/g range. Most WHWTs with liver disease have raised liver copper concentrations but not at a level that would be expected to cause disease, so why these individuals develop hepatitis is unclear. The situation in these WHWTs is the same as in most other breeds of dogs with chronic hepatitis in which the cause of the disease is uncertain. The possibility that, in these cases, autoimmune disease may be the cause has been considered but no conclusive evidence has been found (Johnson 2000). Other diseases that can cause chronic hepatitis are caused by the side effects of some drugs (eg anticonvulsants) and infectious diseases such as canine viral hepatitis or leptospirosis (Centre 1999).

The clinical signs can vary widely and usually start with vague, non-specific changes (Johnson 2000). These include:

depression, weight loss, vomiting, deterioration of general condition, polydipsia (increased frequency of drinking) and polyuria (increasing frequency of urination) with or without jaundice (yellowing of mucous membranes and skin –in this case due to liver failure) and ascites (fluid build-up in the abdomen that gives the affected animal a swollen-bellied appearance) (Johnson 1995, Sevelius & Jönsson 1996, Rutgers & Rishniw 2005). Liver failure can lead to coagulopathies (defects of blood clotting) as the substances in the blood that are involved with clotting are manufactured in the liver. When there are deficiencies in clotting factors, excessive or prolonged bleeding may occur after minor trauma or with gastrointestinal ulceration. Where there is bleeding into the stomach or intestine tarry, black faeces (melaena) may be apparent (Johnson 2000).   

The prognosis (outlook) for individuals with these advanced signs of the disease is poor but if the disease is detected early, the prognosis is better. The extent of permanent liver scarring, fibrosis and cirrhosis is crucial to the prognosis and this can be determined by examination of liver biopsies under the microscope (Johnson 2000). If the liver is so scarred that little normal functioning tissue remains, the outlook is very poor. Some dogs may appear to become ill quickly due to chronic hepatitis because the great reserve capacity and self-repair ability of the liver masks the extent of disease until a catastrophic late stage failure. There will usually, however, be some evidence of more chronic (long-term) effects such as weight loss, and clinical investigations may reveal low blood protein levels or scaring of the liver tissue.

When excessive copper is found in the liver but the disease is not too advanced, treatment to reduce further copper accumulation may be possible. This includes administration of drugs which decrease the absorption of copper, and of others that increase its excretion (Rutgers & Rishniw 2005).

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2. Intensity of welfare impact

The welfare problems caused by chronic hepatitis in West Highland white terriers are very variable, ranging from mild in the early stages of the disease to severe in the later stages. In acute cases, affected dogs feel extremely ill, with possible nausea and generalised weakness. Chronically ill animals may feel ill for months or years until their death. Chronic hepatopathy significantly reduces life expectancy in untreated, and some treated, individuals.

Some of the treatments and diagnostic tests can, themselves, have adverse effects on welfare. For example, the drug D-Penicillamine, which may be used to treat copper accumulation, may cause vomiting or anorexia. Treatment of acutely ill dogs and diagnostic tests may involve invasive techniques (liver biopsy is required to make the diagnosis and check for accumulation of copper in the liver), hospitalisation and trips to and from the veterinary practice which may cause distress to some dogs

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3. Duration of welfare impact

The disease usually appears in West Highland white terriers in middle age, with most dogs being affected when four to eight years old (Andersson & Sevelius 1991). Animals may die of the acute form of the disease within days of signs appearing. In the chronic disease, the animals may be ill for months before dying. When severe liver cirrhosis is present the dog is not likely to live for more than a few weeks but in less severe cases the animals may live for years (Sevelius 1996).

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4. Number of animals affected

West Highland White terriers are known to be predisposed to the disease (Andersson & Sevelius 1991, Thornburg et al 1986, Thornburg et al 1996) but we are not aware of any data on its prevalence. In one study, it was reported that the disease occurred 10 times more frequently in WHWTs than in other dogs (Andersson & Sevelius 1991). Of the 17 WHWTs with clinical liver disease studied by Thornburg et al (1996), two had copper toxicosis and 15 had chronic hepatitis not associated with high copper levels.

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5. Diagnosis

Because of the known breed predisposition, any West Highland white terrier with suggestive signs may be suspected of having chronic hepatopathy. However, similar signs can occur in other conditions and confirmation depends on a full examination with blood and urine tests and often involving X-rays and ultrasound of the liver. These tests also help determine the stage of the disease and degree of liver damage and failure. Definitive diagnosis is made by biopsy of the liver and examination of the tissue under the microscope using specific staining techniques to reveal copper accumulation. Measurement of the tissue concentration of the copper that has accumulated is also useful in this breed (Johnson 2000).

Return to top

6. Genetics

The breed predisposition to this disease strongly suggests that chronic hepatitis has a significant genetic component in the WHWT (Andersson & Sevelius 1991, Thornburg et al 1986, Thornburg et al 1996). It is also known that copper tends to accumulate in the livers of dogs of certain WHWT families, which is further evidence that the condition has a genetic basis (Thornburg et al 1996). However, as far as we are aware there have been no investigations into the genes involved and the type of inheritance has not been determined (Johnson 2000).

It may be that the tendency to develop chronic hepatitis and the tendency to accumulate copper are due to separate genetic abnormalities.

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7. How do you know if an animal is a carrier or likely to become affected?

It is not known if carriers exist for this condition: that is, if dogs may pass the disease onto the offspring without ever developing the disease themselves. It is currently not possible to predict which dogs may develop the disease (a potential test has been evaluated but it is not available at present (Brewer et al 1992), although dogs with affected relatives are more likely to develop the disease themselves (Thornburg et al 1996).

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8. Methods and prospects for elimination of the problem

It is currently unclear if chronic hepatopathy in WHWTs is a single disease with a single cause. Nor is it entirely clear how the known familial tendency to accumulate copper in the liver is associated with development of the disease. The genetic basis and mode of inheritance of these conditions is also unknown and so it is difficult to devise breeding strategies to eliminate them. In such a situation, animals affected by the disease should not be used for breeding (they are often beyond breeding age or too ill to be used for breeding anyway). Because of the suspected genetic basis of the disease, it is probably also sensible to avoid breeding from any animals which has a close relative that has been affected.

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9. Acknowledgements

UFAW is grateful to Rosie Godfrey BVetMed MRCVS and David Godfrey BVetMed FRCVS for their work in compiling this section.

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10. References

Andersson M and Sevelius E (1991) Breed, sex and age distribution in dogs with chronic liver disease. Journal of Small Animal Practice 32: 1-5

Brewer GJ, Schall W, Dick R, Yuzbasiyan-Gurkan V, Thomas M and Padgett G (1992) Use of Copper Measurements to Diagnose Canine Copper Toxicosis. Journal of Veterinary Internal Medicine 6: 41–43

Center SA (1996) Chronic hepatitis, cirrhosis, breed-specific hepatopathies, copper storage hepatopathy, suppurative hepatitis, granulomatous hepatitis and idiopathic hepatic fibrosis.  In Strombeck’s Small Animal Gastroenterology (3rd ed.) pp705-765 WB Saunders: Philadelphia, USA

Centre SA (1999) Chronic liver disease: current concepts of disease mechanisms Journal of Small Animal Medicine 40: 106-114

Johnson SE (2000) Diseases of the Liver in Ettinger SJ and Feldman EC’s (Eds) Textbook of Veterinary Internal Medicine 5th Ed. pp 1298-1325 WB Saunders: Philadelphia, USA

Ludwig J, Owen CA Jr, Barham SS, McCall JT and Hardy RM (1980) The liver in the inherited copper disease of Bedlington terriers. Laboratory Investigations 43: 82-7

Rolfe DS and Twedt DC (1995) Copper-associated hepatopathies in dogs. Veterinary Clinics of North America Small Animal Practice 25: 399-417

Rutgers C and Rishniw M (2005) Copper Storage Hepatopathy. VIN Associate. http://www.vin.com/Members/Associate/Associate.plx?DiseaseId=120. Accessed 11.4.11

Sevelius E (1996) Diagnosis and prognosis of chronic hepatitis and cirrhosis in dogs. Journal of Small Animal Medicine 36: 521-8

Sevelius E and Jönsson L (1996) Liver Disease in Thomas DA, Simpson JW and Hall EJ (eds) Manual of Canine & Feline Gastroenterology. pp 191-220. BSAVA: Cheltenham, UK

Spee B, Arends B, van den Ingh T, Penning LC and Rothuizen J (2006) Copper Metabolism and Oxidative Stress in Chronic Inflammatory and Cholestatic Liver Diseases in Dogs. Journal of Veterinary Internal Medicine 20: 1085–1092

Thornburg LP, Shaw D, Dolan M, Raisbeck M, Crawford S, Dennis GL and Olwin DB (1986) Hereditary copper toxicosis in West Highland white terriers. Veterinary Pathology 23: 148- 154

Thornburg LP, Rottinghaus G, Dennis G and Crawford S (1996) The relationship between hepatic copper content and morphologic changes in the liver of West Highland white terriers. Veterinary Pathology 33: 656-61

© UFAW 2011


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