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12/26/12

Types and Causes of Canine Liver Disease

Trauma

Animals that receive a severe and blunt blow to the front of the abdomen can suffer from liver disease. The most common cause of this type of blow is being hit by a car. A liver lobe can be fractured and bleed into the abdomen, even leading to death. A more common occurrence is a bruise (contusion) that heals itself. Heatstroke, diaphragmatic hernia and liver lobe torsion can also cause liver problems.

Pancreatitis


The severe inflammatory process that occurs with digestive enzymes can spill over into the liver and cause severe disease. The close proximity of the pancreas to the liver and the bile ducts results in some degree of hepatitis whenever there is a case of pancreatic inflammation. Treat the pancreatitis and the liver disease will regress.


Anemia


Hemolytic anemia can decrease the oxygen available to liver cells and lead to their death.

An inflamed liver is called hepatitis.

Trauma can cause this, along with drugs, viruses, bacteria, bile, and toxins

Infectious Hepatitis


Typically caused by either an adenovirus or a herpes virus. Transferred from dog to dog by oral contact and ingestion. Usually only causes a transient non specific illness characterized by lethargy, vomiting, diarrhea and fever. Sometimes develops into a full blown case of severe hepatitis with many of the symptoms previously noted. Treatment is geared to support while the body fights off the bug. Prevention is by vaccination.

Bacteria, viruses, and fungi can all cause liver disease.

Since bacterial infection is common in many liver problems it is routine to use antibiotics when treating liver problems. Specific diseases include Infectious canine Hepatitis, canine Herpesvirus, Leptospirosis, abscesses, histoplasmosis, coccidiomycosis, and Toxoplasmosis.

Several bacterial causes of hepatitis are known. Treatment is based on a proper diagnoses and appropriate antibiotic use. There is good proof that the bacteria is a normal inhabitant of the liver and only becomes a problem when the liver is injured form other causes. There are notable exceptions.

*Leptospirosis is a bacterial infection common in wildlife and transferable to domestic animals and
people through contaminated water. Dangerous, possible fatal, but the vaccine is quite good for prevention.

Certain parasites will infect the liver.

Typically the likelihood of parasitic infestation depends on the area you live in. Diagnosis is often based on symptoms, fecal examination, and standard diagnostic techniques for liver disease. Treatment is the use of appropriate parasiticides.

Chronic Hepatitis


*Copper storage Diseases


Primarily found in Bedlington Terriers, Doberman Pinschers, and
West Highland White Terriers. These are all genetically inherited diseases
which result in abnormal and toxic levels of copper to be stored in
the liver. The course of the disease is variable, some presenting with
acute hepatitis, many presenting in end stage cirrhosis of the liver.
Diagnosis is based on liver biopsy. Treatment requires the use of copper
binding drugs, anti inflammatory to decrease liver inflammation, dietary
modification to limit copper uptake.

Chronic Active Hepatitis


In humans there is a chronic form of hepatitis characterized by chronic elevation of liver enzymes and biopsy samples showing scarring and active inflammation. The underlying cause for this entity falls into one of three categories: viral induced, toxin induced, and immune mediated. There is some question as to whether a similar syndrome exists in dogs.

There has been cases which did show chronic elevation of the liver enzymes over weeks to months), symptoms characteristic of liver disease ill defined malaise), and a response of anti inflammatory treatment to limit the ongoing inflammation and scarring of the liver. At this time recommendations
for treatment are that moderate or intermittent disease should only receive supportive therapy or basic nursing, while deteriorating chronic cases should receive steroid based anti inflammatory. If the case shows poor response, biopsies should be referred to a pathologist for evaluation in an attempt to find the underlying cause. In some cases it may be necessary to use strong immune suppressant drugs to stop the destruction of the liver.

Hepatoportalfibrosis


Disease primarily of the blood supply to the liver. Diagnosed by very specialized radiograph techniques which measure and visualize the blood flow through the liver; Biopsy critical for diagnosing location
of lesion.

Heartworms


These worms can block blood flow into the liver and cause liver failure. Any disease that can cause failure of the right side of the heart can also cause liver problems.

Toxins


Primary disease is caused by the ingestion, injection, or inhalation of a toxic substance which adversely affects the liver. Due to the central nature of the liver with regards to detoxification of chemicals, it is no surprise that many are harmful to the liver. Factors contributing to the disease are: Gender (females more susceptible), fatty diets more dangerous, continuous exposure, high levels of exposure to toxins. Exposure results in death and inflammation of the liver cells, followed by replacement of damaged tissue by fibrous scarring. This can be a self perpetuating cycle, resulting in cirrhosis of the liver.

Toxins include many common drugs, such as acetaminophen, ASA, anabolic steroids, chemotherapy drugs, some antibiotics, glucocorticoids, anaesthetics, parasite control drugs, and phenylbutazone.
Some of the drug induced hepatitis is a predictable side effect of the drug, while other incidences of hepatitis are considered an unpredicted or abnormal side effect of the drug. This is difficult to diagnose unless there is a known exposure to the drug or toxin and the appropriate tests are taken. Biopsy will confirm liver destruction, inflammation, and fibrosis, but it will not single out the causative agent.

Glucocorticoid Hepatopathy


Dogs seem abnormally sensitive to glucocorticoid drugs (“cortisone”) and will develop typical lesions in the liver after multiple dose therapy or long term over production of intrinsic cortisone by the adrenal gland (Cushing’s disease). Lesions are fairly typical and the rare animal which shows liver associated symptoms during glucocorticoid therapy will improve with the removal of the steroids. Liver associated lesions may take weeks to months to heal.

Anticonvulsant Associated Hepatopathy


Phenobarbital, primidone, phentoin, May cause liver disease in 6 to 15 % of all dogs on anti-convulsant therapy. Inflammation seems related to dose. Degree of disease is variable and unpredictable. Diagnoses based on history, symptoms, laboratory tests, and biopsy. Treatment is removal of offending agent.

There are literally thousands of chemicals that could be toxic to the liver. A few examples of these chemicals that are commonly used to treat ill animals include:

  • Rimadyl (arthritis treatment)
  • Thiacetarsamide (heartworm treatment)
  • Ketaconazole (fungal treatment)
  • Tylenol (acetaminophen)
  • Glucocorticoids (cortisone)
  • Anthelmintics (worming medication)
  • Parasiticides
  • Phenobarbital (epilepsy medication)

Portal Vascular Abnormalities


Usually occurs when a portal-systemic shunt allows blood to pass from the digestive tract directly into the general circulation without being detoxified by the liver first. Usually a congenital defect restricted to young dogs and puppies, but can be the result of hepatic cirrhosis. Symptoms are never consistent, but many dogs are young, malnourished, chronically sick, poorly tolerant of toxins, drugs, and anesthetics, and tending to eat strange items (pica). Diagnosis is based on physical exam, history, laboratory tests, and specialized X-rays showing blood flow through the liver. Treatment is surgical correction of the circulatory abnormality to force the blood into the liver prior to it entering the general circulation.


Cancer


Cancer can arise directly within the liver (primary) or spread from elsewhere (metastatic or secondary) through the circulatory or lymphatic systems. In the anatomy section we mentioned the dual blood supply to the liver; the portal vein and the hepatic artery. This extra blood supply increases the chance that a tumor in a different organ that has spread into the bloodstream will end up in the liver. As mentioned in the physiology section, liver cancer is usually detected only after the disease is well established, since functional reserve capacity allowed the liver to function normally for a prolonged period of time.

Some of these liver cancers include:


PRIMARY:
  • Lymphosarcoma
  • Hemangiosarcoma

METASTATIC:
  • Adenocarcinoma
  • Leiomyosarcoma
  • Mammary tumors
  • Oral carcinoma
  • Lymphosarcoma
  • Hemangiosarcoma

Metabolic diseases that cause secondary liver problems:

  • Hypothyroidism
  • Diabetes Mellitus
  • Pancreatitis
  • Hyperthyroidism
  • Cushing’s Disease
  • Inflammatory Bowel Disease
  • Hypoadrenocorticism
  • Protein-losing enteropathy


Cirrhosis


Cirrhosis of the liver can occur as the end result of several liverdiseases, which may be why it is hard to find information on this condition as a separate entity. Cirrhosis can occur in copper storage diseases of the liver, as the end result of idiopathic chronic hepatitis (also called chronic active hepatitis, chronic canine inflammatory hepatic disease and probably other names), as a breed related disorder (several terrier breeds, Dobermans, Labs, cockers and standard poodles), due to anti-seizure medications and possibly due to carprofen and oxibendazole (a dewormer). It is sometimes the end result of infectious illnesses, especially leptospirosis and infectious canine hepatitis (pretty rare now).

Of these conditions, the one that usually shows up without much warning is the idiopathic chronic hepatitis. This condition can sometimes go on for long periods of time with no really obvious clinical signs and affected patients may have markedly decreased liver size and function when the condition finally causes clinical signs. Even at this point it is often possible to help make patients feel better for some time, though. The usual recommendations are to use a low to moderate protein diet to try to decrease the liver’s work load, use metronidazole or neomycin orally if there are signs of central nervous system disturbance, to give lactulose for the same reason, to consider the use of cholchicine, ursodiol (Actigal Rx), SAMe (Denosyl SD-4 Rx), copper chelating agents if necessary and to provide general supportive care, such as gastrointestinal protects if GI ulceration occurs, fluid therapy if there is dehydration, Vitamin K if blood clotting problems occur, and possibly Vitamin E as an anti-oxidant. In liver disease, at least if copper toxicosis is possible, it is best to avoid Vitamin C supplementation as it can make the copper toxicity worse.

As the diseases mentioned above progress, they slowly destroy liver cells, resulting in scarring and an increase in fibrosis in the liver, or cirrhosis. Some patients live for extended periods of time even after it is clear that they have reached the stage that liver cirrhosis is occurring. It can be pretty hard to go back at the time that there is cirrhosis and to figure out why it occurred, so when the liver disease is discovered at this stage, it may not be possible to give you information on the underlying disease and thus the diagnosis of cirrhosis, rather than a more specific diagnosis.

New and Emerging Liver Diseases

Hepatocutaneous Syndrome


Also Known As: necrolytic migratory erythema, superficial necrolytic dermatitis, and metabolic epidermal necrosis

Transmission or Cause: Hepatocutaneous syndrome is a disease characterized by degeneration of the skin cells likely as a consequence of a nutritional imbalance, resulting from metabolic abnormalities caused by severe liver dysfunction or a pancreatic tumor.

Affected Animals: Hepatocutaneous syndrome is a disease that generally affects older dogs with no consistent breed predisposition. There have been very few reports of cats affected by hepatocutaneous syndrome.

Clinical Signs: Skin disease is the usual presenting complaint, although some dogs will exhibit systemic illness (lethargy, poor appetite, weight loss) prior to the skin eruptions. The skin lesions frequently occur in areas of trauma such as the muzzle, lower legs, and footpads. Lesions can also affect the mouth, ear flaps, elbows, and genitalia. Most lesions consist of crusting, erosions or ulcerations, but blisters may also occur. Footpads are often severely thickened and fissured and are often painful.

Diagnosis: Diagnosis is based on supporting history, physical examination, bloodwork abnormalities (such as elevated liver enzymes and low protein levels), and skin biopsy results. Abdominal ultrasonography frequently reveals a pathognomonic “honeycomb” pattern of the liver (due to liver degeneration) or less commonly a pancreatic tumor. In cats, the most common finding is a pancreatic tumor.

Treatment: If a pancreatic or liver tumor is identified and able to be surgically excised, the skin lesions may normalize for an extended period of time, but because these tumors metastasize (spread to other areas of the body) quickly, surgery is not curative. In cases of end stage liver disease, surgery is not possible, and the goal of therapy is to increase quality of life and decrease uncomfortable skin lesions with supportive care and addressing the nutritional abnormalities. Supportive care includes supplementing protein and necessary minerals and enzymes through the diet and oral supplements or by weekly intravenous amino acid infusions that are performed in the hospital on an outpatient basis until improvement in the skin is noted. Unfortunately, despite the supportive care, the disease will progress.

Prognosis: As this disease is a cutaneous marker for serious internal disease, the prognosis is poor with a survival time of less than a year in most cases.

Idiopathic Vacuolar Hepatopathy


This is a diagnosis frequently observed in older dogs. These cases appear typical of steroid hepatopathies based on histopathologic examination and abnormal serum ALP, but without clinical or laboratory evidence of hyperadrenocorticism. The liver of these dogs contains excess glycogen, and they have laboratory findings of predominately G-ALP isoenzymes. One is unable to make the diagnosis of hyperadrenocorticism based on lack of typical clinical signs and normal conventional adrenal testing (i.e., ACTH stimulation or low-dose dexamethasone suppression test). Several dogs recently discovered having vacuolar hepatopathy and increased serum ALP without overt hyperadrenocorticism have abnormal concentrations in some of the other adrenal steroids (i.e., sex hormones such as progesterone and 17alpha-hydroxy-progesterone). It has been documented that progestin steroids bind to hepatic glucocorticoid receptors and will induce a steroid hepatopathy when given orally to dogs. There is now speculation that increases in progestin steroid hormones may result in the hepatic changes and serum ALP increase. It appears that most, if not all, of these dogs live a prolonged life without adverse consequences from their liver disease. The reason for abnormal progestin levels may be secondary to adrenal adenomas, adrenal enzyme deficiency for converting precursors to cortisol or inapparent adrenal masses. Adrenal adenomas have been shown to secrete high levels of 17-hydroxyprogesterone in dogs.

Recently a disproportionate number of Scottish terriers have elevated serum ALP and hepatic vacuolar changes, suggesting a breed predisposition for this condition. They may have a genetic defect in ALP production.

Hepatic Nodular Hyperplasia


Nodular hyperplasia is a benign process causing an increase in serum hepatic values and histomorphologic changes that include macroscopic or microscopic hepatic nodules containing vacuolated hepatocytes. Liver function remains unchanged. Grossly, the appearance may be suggestive of chronic hepatitis or neoplasia. The cause is unknown but appears to be an aging change in dogs; most of those affected are older than 10 years of age. Laboratory findings include a serum ALP increase, but some may have mild increases in serum ALT and AST concentrations as well. Ultrasound study may be normal or may demonstrate larger nodules (many can be only microscopic and not observed on ultrasound study). Biopsy confirms the diagnosis; however, a wedge section is preferred, as a needle biopsy may not demonstrate the nodules. There is no specific therapy.

Gallbladder Mucocele

Gallbladder mucocele is seen in an enlarged gallbladder with immobile stellate or finely striated patterns within the gallbladder on ultrasound study. Changes often result in biliary obstruction or perforation. Smaller breeds and older dogs were over-represented, with Cocker Spaniels being most commonly affected. Most dogs are presented for nonspecific clinical sign,s such as vomiting, anorexia and lethargy. Abdominal pain, icterus and hyperthermia are common findings. Most have serum elevations of total bilirubin, ALP, GGT and variable ALT. Ultrasonographically, mucoceles are characterized by the appearance of stellate or finely striated bile patterns (wagon wheel or kiwi fruit appearance) and differ from biliary sludge by the absence of gravity-dependent bile movement. The gallbladder-wall thickness and wall appearance are variable and nonspecific. The cystic, hepatic or common bile duct may be of normal size or dilated, suggesting biliary obstruction. Gallbladder-wall discontinuity on ultrasound study indicates rupture, whereas neither of the bile patterns predicted the likelihood of gallbladder rupture. Mucosal hyperplasia is present in all gallbladders examined histologically, but infection is not present with all cases, suggesting biliary stasis and mucosal hyperplasia as the primary factors involved in mucocele formation. Cholecystectomy is the treatment for mucoceles.
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