Liver Disease: Signs, Symptoms, and Diagnosis

Written by CKCSCC

From Column written by: Dr. Fleming, Sherwood Animal Clinic (Regina, Saskatchewan, Canada)

Description

If you asked ten people on the street what they knew about "liver", I would bet that the only consistent answer you would get is that it tastes really bad unless the cook really knows his stuff. The best description of the liver I can give you is that this organ is the main industrial centre of the body. The liver processes raw materials, manufactures the building blocks of the body, recycles the old to make new, and detoxifies the industrial waste of the body. In short the liver is involved in just about every biochemical process required to run the body. As a result of this relationship, liver disease can affect just about any other part of the body and thus the symptoms of liver disease are typically unpredictable and non-specific. Furthermore, because the liver acts as a "biochemical cross roads" for the body, it is affected by a wide range of diseases, including viral and bacterial infections, degenerative and neoplastic disease, and toxic insults. It is estimated that three per cent of all disease seen by veterinarians is liver based.

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The liver has a double edged nature which, while being life preserving, makes diagnoses and treatment of liver disease extremely difficult. The liver has a tremendous reserve capacity, which means that it can easily perform its duties with up to 70 to 80 per cent of the liver mass affected by disease. While it certainly is a benefit that our liver can keep us alive despite an overwhelming infection or a massive tumour, it also means that the disease is well advanced and possibly untreatable before any symptoms are noted. We all know that disease is most easily conquered early, but the very nature of the liver makes this an impossible task. One thing about livers though: they are the only organ in the body which is capable of complete regeneration and thus if we do manage to successfully treat the disease, there is a chance of complete recovery.

Clinical Signs

All, some, or only one of these signs may be present.

Intermittent recurrent abdominal or gastrointestinal upsets. loss of appetite, vomiting, diarrhea, constipation.
Progressive depression or lethargy - does not want to play anymore or refuses to go for walks.
Swollen belly with a "fluid filled" look. This is also known as ascites and is actually fluid accumulation in the belly due to circulation alterations in the abdomen.
Pale gray feces. Bile pigments are what gives poop its characteristic brown colour and if the liver is not processing bile properly, the feces will not get their colour.
Orange urine. The improper processing of bile results in the excretion of bilirubin in the urine in high amounts, thus orange urine.
Jaundice, also known as icterus. Any pale or white skin or visible tissue takes on a yellow hue. Again the biliary pigments are accumulating in the body because the liver is not processing them.
Rarely: bleeding problems. Many of the proteins required for proper blood clotting are created in the liver. Remove these proteins and blood clotting decreases.
Hepatic encephalopathy, or severe neurological signs - behavioural changes, seizures, aimless pacing or circling, head pressing. May be associated with meal time.
Pain associated with the abdomen. This is due to the stretching of the liver capsule. May be noted when the dog is lifted around the belly or when the veterinarian probes (palpates) the abdomen. The veterinarian may also notice a swollen liver while palpating with some of the more acute liver diseases.
Chronic weight loss or wasting. The liver processes all the building blocks. If it fails to process, the body fails to maintain itself. Weight loss is very common in chronic liver failure.
Increased water consumption and urination. Most likely due to dramatic shifts in serum and kidney salt balances. May be behavioural too.

Diagnosis

1. Examination, specifically noting signs which may indicate liver disease. Periodic ascites, intolerance of a high protein diet, icterus, chronic weight loss, abnormally coloured feces or urine, bleeding disorders, chronic illness, and all that has been mentioned above. Sometimes urinary crystals formed from the improperly metabolized proteins and amino acids may indicate liver disease.

2. Extensive blood work:

? A complete blood count to check for anemia and blood cell abnormalities.

? A complete chemistry screen, including ALT, ALP, AST, bilirubin, glucose, urea, electrolyte levels, albumin, globulin and bile acid levels. The bile acid levels should be checked on a empty stomach and two hours after feeding. All these values , with the exception of the bile acids, usually are included on a standard Small Animal Data Base Screen.

? A complete urine analysis. Check urobilinogen levels, bilirubin levels, glucose levels, protein levels. Again all this is usually on a standard urinalysis panel.

? Radiograph the abdomen. X rays can show increased liver size, decreased liver size liver abscesses, abnormal mineralization , and circulatory abnormalities (using special dyes)

? Ultrasound the liver. Perfect technique for visualizing the circulation of the liver, the bile duct system, the density of the liver tissue, the size of the liver.

? Biopsy of the liver. While this is a surgical technique, it is the ultimate for diagnoses, since it allows us to directly examine and test liver tissue, give an absolute diagnoses and hopefully a final treatment regime. Biopsies can be taken by full laparotomy, where the surgeon actually looks at the liver and removes a small piece, or they can be done by a biopsy needle guided by ultrasound through the body wall. The liver will regenerate any piece removed, therefore liver biopsy is usually a low risk procedure in capable hands.

Specific Diseases of the Liver

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 characterised 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.

Another syndrome has been seen in England called Canine Acidophil hepatitis. Typical signs of hepatitis are present, but the case may take a very chronic course, lasting over a period of years. No specific viral organism has been identified, therefore no vaccine or treatment is available.

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.

Blastomycosis, histoplasmosis and coccidiomycosis are fungal infections seen in various parts of the country (usually associated with river systems). Difficult to treat.

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.

Tuberculosis is still around and is considered transmissible to humans.

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

Liver Disease Secondary to other Disease

Acute pancreatitis: 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.

Chronic bowel disease: the chronic inflammation of the bowel allows portal absorption of toxic intestinal products and bacteria. Treat the colitis.

Shock, anemia, and congestive heart failure. All these result in severe loss of blood circulation to the liver and lack of oxygen. The liver disease is rarely of primary concern as the primary causes of the problem are most likely going to kill the animal prior to liver failure.

Abdominal trauma: tears, bruising, biliary leakage, hepatic bleeding. Correction of these problems would require surgical intervention, assuming a timely diagnoses. Simple bruising of the liver will heal unaided, with only a transient increase in the hepatic enzymes.

Chronic Hepatitis

Copper storage diseases in Beddlington 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. Diagnoses 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 characterised 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 have 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.

Leptospirosis associated chronic hepatitis: An example of bacterial infection leading to chronic disease. Diagnoses by biopsy and identification of the pathogen. Treatment by antibiotics.

Infectious Canine Hepatitis associated chronic hepatitis. Exposure to the virus responsible for ICH leads to chronic active hepatitis due to an ongoing immune system malfunction. Diagnoses by biopsy and the use of special stains to demonstrate the viral antigens in the liver.

Lobular dissecting hepatitis: rare disease diagnoses by biopsy.

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.

Toxic liver injury: 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: 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.

Cirrhosis: This is the end point of chronic, active hepatitis. The cycle is one of liver cell death (due to insult, either toxic, viral, or immune mediated), followed by inflammation and scarification. No treatment is possible and ongoing palliative and dietary care is the only treatment option.

Noninflammatory Liver Diseases

Portal vascular abnormalities Usually a portal-systemic shunt. See separate topic for details.

Hepatic Cancer (Neoplasm) Falls into two categories: primary or originally stemming from liver tissue or secondary; originating in some other part of the body and spreading to the liver through the circulation system.

Primary liver cancers can stem from exposure to toxins (oncogenic compounds) which attack the liver full strength, since the liver is the primary detoxification centre of the body.

Secondary cancers may stem from any part of the body, but the liver is a favourite destination for metastatic cancer because of its central function in the body and the micro-capillary network which makes up the circulation passing through the liver.

Primary liver cancer is usually quite advanced prior to diagnoses and tends to metastasize to the rest of the body very early in the course of the disease.

Keep in mind the liver can function with less than one third of its volume still operating, therefore liver cancer can be very advanced before any symptoms are noted.

Treatment is usually pointless, but would be based on diagnoses of the specific cancer and the use of appropriate chemotherapy agents.

Therapy

1. Removal of toxic agents. Identify and remove any drug or toxin which may potentially hurt the liver.

2. Rest and confinement. This will help divert body resources to the healing process at the liver and reduce discomfort caused by inflammation of the liver such as painful belly, nausea, malaise.

3. Dietary management: Extremely important. The goal is to provide all the necessary nutrients which may be lost due to failure of liver processing without overtaxing the liver with regards to processing of dietary intake. High levels of top quality protein to provide the essential amino acids in an easily digestible carrier which will not produce high levels of ammonia during digestion. Cottage cheese is good, meat tends to produce high levels of ammonia. High level carbohydrates to drive the metabolism of the body, essential fatty acids not less than 6% of the daily intake, and a good mineral and vitamin supplement. Force feeding may be necessary.

4. Control of ascites and water retention. Reduce sodium intake. Diuretics will help in resistant cases.

5. Control concurrent infections with antibiotics.

6. Deal with the concurrent medical problems as they crop up. Remember that the dog may develop bleeding problems, malabsorption problems, and neurological problems. Each separate problem has to be dealt with both individually and as a part of the whole disease entity. Neurological symptoms such as coma need to be addressed aggressively with a combination of therapies.

The author reports this information was taken from a single source Textbook of Veterinary Internal Medicine edited by Stephen J.Ettinger 1989.

References

http://www.geocities.com/Heartland/Plains/1151/LiverDisease.html

Additional Reading

Diseases of the Liver, The Health of Your Dog, John Bower & David Youngs, Alpine Publications Inc., 1989, p. 87.

The Liver, Pancreas and Disorders, by Donald R. Strombeck, in U.C. Davis School of Veterinary Medicine Book of Dogs, HarpersCollins Publishers, 1995, p. 305-308.

Websites

PORTOSYSTEMIC OR LIVER SHUNTS

Description

First, from http://www.vetinfo4dogs.com/dshunt.html an explanation of how shunts develop:

Liver shunts are a congenital problem in some dogs. During gestation the placenta delivers blood with food and oxygen from the mother through the umbilical vein. This means that in the fetus, circulation is the reverse of circulation after birth, because the fetus' veins have the oxygenated blood and arteries return unoxygenated blood to the heart. In order to make this work, there is a shunt from the liver venous circulation to the arterial circulation. At birth, the pressure within the circulatory system changes as respiration occurs and this shuts the shunt, which eventually disappears. If this reverse in circulation doesn't happen for some reason, the liver is deprived of a blood supply and doesn't develop properly after birth. Many puppies can live with the small functioning portion of the liver for some time but eventually have problems and usually die if the situation is uncorrected. It is possible to surgically close the shunt and the surgery works well.

Normally, the blood carries toxins and toxic by-products of metabolism from the stomach and intestines to the liver, where the toxins are removed. "In animals with portosystemic shunts, the blood bypasses the liver and is diverted to another blood vessel, allowing toxins to circulate through the body," says Dr. Jennifer Brinson, a veterinarian who specializes in internal medicine at the University of Illinois College of Veterinary Medicine Teaching Hospital in Urbana.

Shunts can be either congenital--a condition the animal was born withóor acquired--a condition that developed later in life. Congenital shunts are generally diagnosed in animals less than one year old. Acquired shunts can occur at any age and are often caused by liver disease. Shunts are also categorized as intrahepatic (within the liver) or extrahepatic (outside the liver).

Clinical Signs

Dogs with congenital shunts tend to be small for their age and breed. Other signs of shunts include excessive drinking, frequent urination, and a condition known as hepatic encephalopathy. This condition arises shortly after eating and may appear as depression, muscular incoordination, coma, and seizures--signs caused by ammonia (a by-product of protein digestion) reaching the brain instead of being cleared by the liver.

Diagnosis

Diagnosis of a suspected portosystemic shunt is often done in three stages. The first stage is checking a blood and urine sample. If these samples are suggestive of a shunt, second stage tests, consisting of a pre- and post-bile acid test and an ammonia challenge test, are performed. These two tests help determine the functional capacity of the liver. Finally, an ultrasound or nuclear scan may be used to try to locate and determine the extent of the shunt.

Therapy

Treatment and prognosis of shunts depend on their location and severity. "A congenital, single, extrahepatic shunt that is caught early is a good candidate for surgery," says Dr. Brinson. "Intrahepatic shunts commonly must be treated medically."

The medical treatment for portosystemic shunts is aimed at reducing the amount of ammonia circulating in the body and decreasing the symptoms. A low-protein diet and lactulose to reduce absorption of ammonia are prescribed. In emergency cases, enemas with water or lactulose are used to reduce ammonia absorption immediately. If portosystemic shunts go untreated, the symptoms will get progressively worse and eventually the pet may die.

References

Ettinger S. (1989).Textbook of Veterinary Internal Medicine. Philadelphia: W.B. Saunders Company.

Laflamme D.P. (1989). Hepatoencephaopathy Associated with Multiple Portal Systemic Shunts in a Dog. The Journal of the American Animal Hospital Association, 25 (2) 199-202.

Maddison J.E. (1988). Department Veterinary Clinical Studies, the University of Sydney New South Wales 2006. Australian Veterinary Journal , 65(8) 245-249.

Tobias, K. (1993). Disease mechanisms in Small Animal Surgery: Portosystemic Shunts. Philadelphia: Lea & Febiger.

Tobias, K. (1994). Personal Communication

VanGundy, T.E. (1987). Congenital Portacaval Shunt in a Seven-Year-Old Dog. California Veterinarian, 41(3), 19-28.