Liver Disease

Introduction | Causes & Prevention | Symptoms & Signs | Diagnosis & Test | Treatment Options

Liver Disease

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Introduction

The liver is a large, dark red organ located in the front part of the abdomen, just behind the diaphragm. The diaphragm is the physical partition between the thoracic (chest) and abdominal cavities. Conditions relating to the liver are called "hepatic" conditions, much like those affecting the kidneys are called "renal" conditions. "Liver disease" is a very general term used to describe any type of liver disorder.

Causes & Prevention

Causes of Liver Disease in Dogs

There is no one cause of canine liver disease. It can be chronic or acute in onset and can be familial, hereditary/genetic, infectious, toxic, cancerous or of unknown origin, among others. Liver damage or disease can be caused by many things, including the following:

Ingestion of or exposure to high levels of certain chemical toxins, such as insecticides, rodenticides, lead, selenium, arsenic, iron, phosphorus and carbon tetrachloride
Ingestion of toxic levels of certain drugs, such as antifungals, analgesics (pain medications, including nonsteroidal anti-inflammatory drugs/NSAIDs), anticonvultants, antibiotics, anesthetic gases, dewormers, corticosteroids and diuretics. Most adverse drug reactions that lead to liver toxicity are associated with inappropriately high dosage and/or prolonged use
Systemic infectious or other diseases, such as leptospirosis, heartworm infection, infectious canine hepatitis, canine adenovirus, diabetes mellitus, hyperadrenocorticism (Cushing's disease) and hypothyroidism
Cancer (neoplasia), which can be primary (starting in the liver) or metastatic (coming from elsewhere). May involve hepatocellular carcinoma (common), hepatocellular adenoma, biliary carcinoma or adenoma, hemangiosarcoma, leiomyosarcoma, lymphoma, islet cell carcinoma, adenocarcinoma, transitional cell carcinoma and many other forms or cancer
Toxic plants, such as blue-green algae, mushrooms, lillies and ragwort, among many others
Molds, such as aflatoxin
Liver shunts (portosystemic shunts)
Idiopathic chronic hepatitis (usually caused by an unknown autoimmune malfunction)
Copper-associated hepatitis (often breed-related)
Physical obstruction of the bile ducts caused by liver flukes, tumors, pancreatitis or gall bladder stones
Fibrosis of liver tissue
Vascular or circulatory disorders (congenital [present at birth] or developmental)
Biliary tract disorders
Infectious diseases (bacterial, fungal, viral)
Liver abscesses
Trauma
There are thousands of toxic substances that can damage the liver if ingested. Any heart or circulatory problem affecting blood flow to the liver can also cause liver disease.

Regardless of its cause, liver disease typically follows a predictable course, starting with liver swelling and enlargement, called hepatomegaly. As the disease progresses, liver cells begin to die (hepatic necrosis) and become replaced with scar tissue, known as granulation tissue. Over time, the liver becomes increasingly firm, with bands of fibrous connective tissue partitioning the liver into abnormal, irregular, rubbery nodules – a serious condition called cirrhosis. Unfortunately, once the liver becomes cirrhotic, the condition is irreversible. However, if liver disease is detected and treated before this terminal stage, the liver has the ability to regenerate enough tissue to function normally. The extent of functional recovery depends upon the extent of disease at the time of diagnosis. Authorities suggest that at least 70 or 80 percent of liver cells must be permanently damaged before irreversible damage sets in.

Prevention of Liver Disease
Many causes of liver disease are not preventable. Of course, potentially toxic drugs, plants, chemicals and other substances should be kept well out of reach of companion animals, which will prevent exposure to them. Infectious diseases should be diagnosed and treated promptly to prevent liver damage, and routine vaccination protocols should be followed. All dogs should be provided with a high-quality diet, free access to fresh water, warm well-padded bedding and lots of play time to maintain overall health. Annual veterinary examinations, including routine blood tests, can identify elevated liver enzymes which may reflect early liver damage.

Special Notes
Certain infectious causes of liver disease are potentially contagious between dogs, including leptospirosis, infectious canine hepatitis and canine adenovirus. Leptospirosis may be zoonotic, meaning that it may be transmissible from dogs to people.

There are various treatment protocols for dogs with liver disease, depending upon the cause of the condition. The dog's veterinarian is the best one to evaluate the extent of liver damage and recommend an appropriate treatment or management plan. The liver is a remarkably complex organ that can recover from damage or disease in multiple ways.

Symptoms & Signs

Introduction
The liver executes some of the most complex and vital functions in a dog's body. It metabolizes fats, carbohydrates and proteins and is involved in the production of essential blood clotting factors. It synthesizes a number of key enzymes and helps remove ammonia from the bloodstream. The liver also stores vitamins and minerals and aids in the digestion and detoxification of circulating wastes, drugs and poisons.

The clinical signs of liver disease (medically referred to as "hepatobiliary disease") are extremely variable due to the liver's extensive interaction with other organs and its unusual regenerative capacity. More than one-half (and maybe up to 70 or 80 percent) of functional liver tissue must be destroyed before liver failure can be diagnosed.

Symptoms of Liver Disease in Dogs
Some dogs show no clinical manifestations of liver damage, especially in the very early stages of disease. Once symptoms do develop, they usually are nonspecific. The severity of any given symptoms does not necessarily correlate with the severity or extent of liver damage, or with the animal's prognosis. Because the liver is intimately involved in so many essential bodily functions, what appear to be symptoms of liver disease might actually be caused by an abnormality in another organ or organ system. With this in mind, the general signs and physical examination findings often associated with liver disease, irrespective of its cause, include one or more of the following:

Loss of appetite (inappetence; anorexia)
Weight loss
Nausea
Vomiting (often intermittent but usually chronic)
Depression
Lethargy
Disinterest in normal activities (apathy)
Diarrhea (less common than vomiting)
Dehydration
Increased thirst/water intake (polydipsia)
Increased frequency of urination (pollakiuria)
Increased volume of urine output (polyuria)
Weakness
Unkempt hair coat
Abdominal enlargement or distention (bloated appearance)
The distended abdomen is usually caused by an enlarged liver or spleen ("organomegaly," which means an enlarged organ, or more specifically "hepatomegaly" or "splenomegaly"). It also is commonly caused by a build up of fluid in the space between abdominal organs ("effusion" or "ascites") or by poor abdominal muscle tone ("muscular hypotonia").

Some more specific signs of liver disease include:

Jaundice (yellow staining of the serum, skin and mucous membranes caused by build-up of the bile pigment, bilirubin, in circulation. Also referred to as "icterus," jaundice can turn a dog's urine a bright, yellowish-orange color (bilirubinuria). It also frequently causes a yellow appearance to the whites of the eyes and mucous membranes of the tongue and gums.)
Abnormal fecal color and consistency (acholic feces – or changes in fecal color – are caused by an absence of bile pigments in the intestinal tract due to abnormal retention in the blood, which makes the dog's stools pale and putty-colored. This normally indicates complete bile duct obstruction associated with liver disease.)
Spontaneous bleeding disorders (animals with liver disease often have problems with coagulation, or clotting, of their blood, called "coagulopathies". In dogs, the upper gastrointestinal tract – usually the stomach and duodenum, which is the first part of the small intestine - is most commonly affected by coagulation disorders associated with liver disease. This leads to gastrointestinal bleeding/hemorrhage, which owners may detect by seeing blood in their dogs' stools. Affected dogs may also vomit blood and/or have visible blood in their urine.)
Blood in the feces (hematochezia)
Blood in the urine (hematuria)
Blood in the vomitus (hematemesis)
Neurological and behavioral changes
Neurological and behavioral changes in dogs with late-stage liver disease are common. They are caused by high levels of circulating toxins that normally are removed by a healthy liver, but not by a diseased one. When these toxins accumulate in the brain, the dog develops a condition called hepatic encephalopathy, ("hepatic" means emanating from or pertaining to the liver). This often leads to:

Aggression
Agitation
Disorientation
Restlessness
Trembling (tremors)
Circling
Lack of coordination (ataxia)
Staggering
Aimless wandering
Mental dullness
Dementia
Stupor
Pacing
Head-pressing
Blindness
Excessive salivation (drooling)
Generalized seizures
Collapse
Coma
These signs develop in dogs (and cats) with liver disease, because the cerebral cortex of the brain is exposed to intestinal toxins that normally are removed by a healthy liver but escape hepatic detoxification in cases of liver disease. Most gastrointestinal toxins are derived from normal bacterial metabolism - or digestion - of proteins and their byproducts. Ammonia is one of the most common intestinal toxins contributing to the symptoms of hepatic encephalopathy, which can wax and wane over time. Hepatic encephalopathy tends to be a chronic condition which cannot be cured, but often can be controlled.

Dogs with advanced liver disease can develop a debilitating skin disorder referred to as hepatocutaneous syndrome. The reason for this condition is not well-understood, but its symptoms may appear before signs of internal liver disease are apparent and include:

Sores/lesions on the footpads (thickened, crusted, ulcerated)
Foot pain
Reluctance to rise, walk, exercise or play
Itchiness (pruritis) of the feet
Redness between the toes (interdigital erythema)
Sores/lesions on the ear flaps, external genitalia, oral cavity, eyes, elbows, lower abdomen or elsewhere
Dogs at Increased Risk
Most forms of liver disease are more common in middle-aged to older animals. However, congenital disorders, such as portosystemic shunts and congenital vascular disease, are more frequently seen in young dogs. Acquired copper storage disorders are more common in Bedlington Terriers, West Highland White Terriers, Skye Terriers, Keeshonds, Labrador Retrievers and Dalmatians. Breeds predisposed to chronic hepatitis include the Doberman Pinscher (mainly seen in females), Cocker Spaniel (males are overrepresented), Labrador Retriever, Standard Poodle and Scottish Terrier. Exposure to hepatotoxins is more frequent in free roaming dogs with access to chemicals, heavy metals, stagnant standing water, pesticides, poisonous plants or drugs. Free roaming dogs are also more likely to suffer acute blunt trauma to their liver. Healthy dogs exposed to dogs that have leptospirosis, canine infectious hepatitis or canine adenovirus infection have a greater risk of developing those diseases, which contribute to liver damage.

Only a skilled veterinary professional can assess a dog and perform the tests needed to confirm a diagnosis of liver disease.

Diagnosis & Tests

Introduction
Liver disease in domestic dogs is a serious medical condition, but it is not necessarily a death sentence. Because the liver is involved in so many diverse bodily functions, the attending veterinarian is likely to recommend a battery of initial tests to assess the condition of the patient's liver. If the results of those tests suggest liver disease, more advance tests may be recommended to confirm the diagnosis definitively. The liver is an amazing organ with a large reserve capacity; upwards of 70 percent of functional liver cells must be damaged before liver failure occurs. The key is to catch liver disease early, so that an appropriate treatment plan can be put in place to help prevent further progression of the disease.

How Canine Liver Disease is Diagnosed
When presented with a dog that just "ain't doing right" (in veterinary speak, a dog that is "ADR"), the first thing that most veterinarians will do is take a complete history of the dog's background from its owner and then conduct a thorough physical examination. She will be looking for any observable abnormalities, such as distended abdomen, pale mucous membranes, poor coat condition, dehydration, signs of jaundice, behavioral changes and/or neurological changes. She may be able to palpate (feel) an enlarged liver or an identifiable mass in the front part of the dog's belly (abdomen).

It is extremely important for an owner to tell his veterinarian about any unusual behaviors or actions that he has noticed in his dog, such as appetite loss, depression, lethargy, weakness, lack of coordination, weight loss, changes in coat condition, nausea, vomiting or diarrhea. The owner should tell the veterinarian about any changes in the volume or color of his dog's urine or stools, and if so what those changes are. He should discuss any changes in behavior or other neurological signs, such as aggression, dementia, hysteria, trembling, circling, ataxia (lack of muscular coordination), staggering, pacing, head-pressing, vision problems, excess salivation, seizures or loss of consciousness.

The next diagnostic step probably will be a series of blood tests, including a complete blood count (CBC) and a serum biochemistry panel. Blood samples are easy to obtain and will undergo comprehensive assessment of the circulating levels of certain liver enzymes and other substances, including albumin, blood urea nitrogen (BUN), bilirubin, cholesterol, glucose and various electrolytes, among other things. The primary enzymes that the veterinarian will assess are alanine transaminase (ALT) and aspartate transaminase (AST), although she also probably will look at the levels of alkaline phosphatase (AP) and gamma glutamyltransferase (GGT). Dramatic elevations in these enzymes usually reflect liver dysfunction, although they do not necessarily correlate with the severity of liver disease. Similarly, serious liver disease can exist in dogs with only mild liver enzyme changes.

Another important diagnostic tool is a serum bile acid concentration test. This involves taking one blood sample after the dog has fasted for 12 hours, and another 2 hours after it is fed a high-fat meal. Both samples are then tested for bile acid levels. Elevated serum bile acid levels are highly suggestive of clinically relevant liver disease. With widely available, rapid and simple methods for determining serum bile acid concentration, this is a convenient and practical test of liver function in domestic dogs.

A urine sample will also be analyzed routinely when liver disease is suspected. The veterinarian will look for the presence of bilirubin and/or ammonium biurate crystals in the sample. The urinalysis will help the veterinarian assess the dog's kidney function. While fecal evaluation rarely provides diagnostic information about liver disease, it can be helpful if there are significant changes in the texture or color of the stool. Pale grey, pasty stools suggest complete bile duct obstruction. Dark red or orange-colored feces can indicate gastrointestinal bleeding or increased bilirubin breakdown, which also frequently accompany liver disease.

Although it is not part of the standard screening protocol described above, another test of liver disease is assessment of the dog's fasting plasma ammonia concentration. Special procedures and laboratories are required for this test, but they are becoming increasingly available to general veterinary practitioners. Elevated plasma ammonia levels after fasting suggest hepatobiliary disease, because a severely damaged liver cannot detoxify and remove ammonia from the blood. A nother confirmatory (but rarely used) test is an ammonia tolerance test, which can be helpful in distinguishing between liver and gall bladder disease.

More advanced diagnostic measures include blood coagulation profiles, abdominocentesis (analysis of free fluid sampled from the abdominal cavity), survey abdominal radiographs (X-rays) and/or ultrasound examination. Veterinary teaching hospitals and large referral practices may be able to perform even more specialized diagnostic imaging procedures, such as nuclear imaging (scintigraphy), magnetic resonance imaging (MRI) and/or computed tomography (CT/CAT scan).

The attending veterinarian may recommend a fine needle aspirate of the liver and/or a liver tissue biopsy in order to definitively diagnose liver disease and assess the dog's prognosis. There are a number of ways to obtain a liver sample, including laparoscopy. The best technique will be determined by the veterinary team based upon whether they believe that the dog's liver disease is generalized or focal. The decision also will be based on the dog's blood coagulation status, clinical stability and fitness for undergoing general anesthesia. A biopsy is an invasive procedure that carries its own inherent risks – including those associated with anesthesia, seeding of infection and hemorrhage in animals with preexisting coagulation disorders. Biopsy samples are submitted to a laboratory for culture and histopathological examination.

Special Notes
Diagnosing liver disease in dogs requires a number of tests that typically are conducted in a specific order over an extended period of time. Using a combination of history, physical examination, blood/urine/fecal tests, coagulation profiles, diagnostic imaging and tissue sampling, a veterinarian should be able to assess the nature and extent of a dog's liver condition, so that an appropriate treatment protocol can be implemented.

Treatment Options

Introduction
The liver is unique in that it has a large reserve capacity and more regenerative capability than almost any other organ. As a result, canine liver disease typically can be treated, or at least managed, if a diagnosis is made early. Treatment depends upon the underlying cause of the condition. The goals of treating liver disease are to eliminate harmful toxins (or minimize their detrimental effects on the liver), promote healing and regeneration of liver tissue, prevent or control complications of liver dysfunction, treat the underlying cause when possible and keep the dog as comfortable and stable as possible until sufficient liver function can be restored. Treatment options include prescription and over-the-counter medications, dietary supplements, lifestyle changes, supportive care, surgical procedures and a number of other possible therapies that the attending veterinarian will discuss with her patient's owner.

Treatment Options
Treatment protocols for dogs with liver disease vary based upon the cause of the condition. Acquired liver diseases in dogs are extremely diverse, especially chronic disorders which are collectively referred to as "chronic hepatitis." Chronic hepatitis in dogs refers to a range of disorders that have similar historical features and clinical signs. Hepatitis can be familial (especially in Bedlington Terriers, Doberman Pinschers, West Highland White Terriers, Skye Terriers and Dalmatians), but it also can be caused by infection, ingestion of certain drugs or toxins or by unknown factors. Treatment options for dogs with liver disease may include some or all of the following approaches and often will be long-term.

Dietary Modification
Dietary adjustments are normally recommended to ensure that a dog with liver disease receives the caloric and nutrient intake necessary to support liver regeneration and to manage the effects of hepatic encephalopathy. So-called "liver diets" are commercially available but can also be homemade. They are designed to contain extremely digestible, high-quality but restricted levels of bioavailable protein, to reduce the metabolic demands on the liver. Protein restriction is important to reduce the levels of circulating ammonia, which comes from bacterial breakdown of protein in the gut. Non-meat protein sources, such as dairy products and eggs, generally are preferred in diets for dogs with liver disease. The attending veterinarian can recommend an appropriate diet, which might include carefully regulated portions of certain carbohydrates, vitamins, proteins, minerals and fats. Dietary sodium (salt) should be restricted in dogs that are retaining excess fluid in their abdomens due to liver disease. In addition to dietary changes, the veterinarian may suggest vitamin or other oral supplements that can promote liver regeneration and improve liver functioning, such as Vitamin E, Vitamin C, Vitamin K, zinc, S-adenosylmethionine ("SAM-e"), milk thistle (silybin) and/or Ursodiol.

Treatment of Copper-Related Hepatitis
For liver disorders associated with abnormal accumulation of copper, the amount of ingested copper must be minimized. There are several commercially available prescription diets, and/or diets that can be made at home, that contain restricted copper levels. The attending veterinarian may recommend supplementation with zinc or copper chelating agents, which help remove these elements from the bloodstream.

Medication
Drug therapy is warranted for many dogs with liver disease. Glucocorticoids ("steroids") have been used to prolong survival times in dogs with liver disease due to their anti-inflammatory and immunosuppressive properties, although their use and appropriate dosage protocols are somewhat controversial. Azathioprine has been used to manage some of the adverse effects of steroid medications. However, azathioprine can contribute to bone marrow damage. Antibiotics are sometimes prescribed to combat bacterial infections, especially when hepatic abscesses are present. Other medications have been used to combat liver fibrosis, including colchicine. Studies of this anti-fibrotic agent in people with fibrotic liver disease show remarkable improvement in symptoms and survival rates. Some dogs have benefitted from its use as well, although reported side effects include diarrhea, vomiting and abdominal discomfort.

Other medications are available to relieve vomiting (emesis), gastrointestinal bleeding and gastric ulcers, if present. These currently include ranitidine, famotidine and omeprazole, sometimes in combination with sucralfate. Lactulose is commonly prescribed in cases of hepatic encephalopathy to increase the dog's gastrointestinal tolerance of proteins. Lactulose is broken down by bacteria in the colon and traps ammonia molecules there, making them non-absorbable and therefore excreted in the dog's feces. Lactulose also changes bacterial metabolism so that less ammonia is generated in the first place. If the dog has seizures associated with its liver disease, barbiturates such as phenobarbital may be recommended, although generally barbiturates are avoided in cases of liver disease.

Other medications will no doubt be developed over time to help treat the causes and consequences of liver disease. Drugs that require metabolism by the liver to become effective (or to be eliminated by the body) are normally avoided, and drugs are prescribed conservatively and in moderate doses in dogs with liver disorders. Protocols for medical management of canine liver disease are rapidly changing based on the results of scientific studies and drug trials.

Supportive Care
Sometimes, liver disorders are treated only with supportive care, although normally supportive care accompanies other treatment methods. Intravenous or subcutaneous fluids may be given to resolve dehydration and restore proper electrolyte balance. Antacids or other medications for taxing symptoms like vomiting and diarrhea can be given. Of course, a safe, calm, quiet, temperature-regulated environment, a healthy diet and free access to fresh water are all essential.

Blood Transfusion
Blood transfusions may be appropriate in dogs that have severe bleeding disorders associated with clotting and coagulation abnormalities caused by liver disease. Fresh whole blood, fresh packed red blood cells or fresh frozen plasma typically are used, because stored blood products contain high ammonia concentrations which are undesirable in most cases of liver disease. High ammonia concentrations contribute to the behavioral and neurological signs associated with hepatic encephalopathy.

Surgery
When a dog has an identifiable liver or gall bladder mass, the treatment of choice usually is surgical removal. Internal hemmorhage is the most common complication of these surgeries, and fresh blood products should be available in case transfusion is necessary before, during or after surgery. Dogs with liver disease are anesthetic risks, because most anesthetic agents are processed by the liver. Chemotherapy and radiation therapy can be used for some forms of liver cancer. Unfortunately, treatment options are very limited for those cancers affecting more than one lobe of the liver, and for those that are metastatic.

Newer Treatment Options in Development
New treatment options are being explored for companion animals with liver disease - especially for those with cancer (neoplasia). These include intra-arterial chemotherapy, trans-arterial chemoembolization, percutaneous ethanol injections, microwave coagulation and various immunotherapeutic strategies. While these potential therapies are beyond the scope of this article, owners of dogs with liver disease may want to discuss them with their veterinarian to determine the most current status of their development, availability and cost.

Prognosis
The liver is a remarkably complex organ that can malfunction and yet recover in multiple ways. Specific treatment protocols and an accurate prognosis depend almost entirely upon the cause and extent of liver dysfunction. Only a veterinarian can assess which treatment methods are best in any given case of canine liver disease and provide an accurate prognosis for the patient in question.

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