The liver is an organ that performs numerous functions, including metabolizing carbohydrates, proteins, and fats. It also breaks down and excretes many potentially toxic compounds. Because of this, the liver is susceptible to injury and disease. Fortunately, the liver has a large storage capacity and functional reserve and is capable of regenerating, which provides some protection against permanent damage.
When liver cells die, they are removed by inflammatory cells and replaced with either new liver cells or fibrous tissue. Although liver disease is common in horses and foals, it does not usually progress to liver failure. The outlook for horses that do develop liver failure is usually unfavorable, unless the problem is short-term and regeneration of new liver cells is evident. Early liver fibrosis may be reversible if recognized and treated promptly. Longterm disease with extensive loss of functioning liver tissue and the development of fibrosis is a grave sign and the outlook for recovery is poor.
Signs of Liver Insufficiency
Signs of liver insufficiency may not be evident until more than 60 to 80% of the liver is nonfunctional or when liver dysfunction is caused by disease in another organ system. Early vague signs of depression and decreased appetite may be overlooked. Jaundice (yellowing of the skin, gums, and whites of the eyes), weight loss, and abnormal behavior due to hepatic encephalopathy (see below) are common in horses with liver disease and liver failure. Skin changes due to a reaction to ultraviolet sunlight (photosensitization), fever, or abdominal pain (colic) may occur. Less often, harsh, high-pitched breathing sounds, diarrhea, or constipation, may be present. Anemia may be seen in horses with liver dysfunction due to parasitic diseases, some plant poisonings, longterm inflammatory diseases, or destruction of red blood cells. Because the liver produces important clotting proteins, horses with severe liver failure may bleed abnormally. Weight loss is a common sign in longterm liver disease and may be the only sign associated with liver abscesses.
Hepatic encephalopathy, a syndrome of neurologic problems caused by poor liver function, is seen in a number of liver diseases. The liver normally removes poisons from the bloodstream; when the liver is not working properly, poisons build up and may affect the nervous system.
Signs of hepatic encephalopathy may include:
depression
lethargy
head pressing
circling
aimless walking
lack of coordination
difficulty swallowing
persistent yawning
sleepiness
increased friendliness
eating of non-food objects (pica)
aggressiveness
vicious behavior
stupor
seizures
coma
Loud sounds while breathing and difficulty breathing due to collapse of structures in the throat occur in some cases of liver failure, especially in ponies. Although the signs can be dramatic, hepatic encephalopathy can often be reversed if the underlying liver disease is successfully treated. Horses with hepatic encephalopathy often show aggressive and unpredictable behavior that can result in injury to the horse or to its handlers. The animal may require sedation.
Liver disease can cause photosensitization, a condition in which the skin is unusually sensitive to ultraviolet sunlight. This disorder is caused by increased levels of a light-reactive chemical called phylloerythrin circulating in the bloodstream. Signs can include itching, mild to severe skin disease with reddened skin, extensive fluid accumulation (edema) beneath the skin, skin ulceration and peeling, eye inflammation and tearing, aversion to light, and cloudiness of the cornea. Skin inflammation and edema are particularly evident on nonpigmented, light-colored or hairless areas of the body (such as the lips and white markings on the face or legs) that are exposed to sun. Uncommonly, the underside of the tongue may be affected. Blindness, skin abnormalities, loss of condition, and occasionally death can result.
Either diarrhea or constipation can occur in horses with liver disease. Ponies and horses with hyperlipemia (high levels of fat in the blood) and liver failure may develop diarrhea, founder (laminitis), and fluid accumulation under the skin (edema). Some horses with liver disease have alternating diarrhea and constipation. Horses with liver failure and hepatic encephalopathy frequently develop intestinal impaction or obstruction due to decreased water intake.
Initially, your veterinarian will treat your horse to reduce the signs of severe hepatic encephalopathy, stabilize its condition, and perform laboratory tests. Your veterinarian will want to perform a liver biopsy to determine the type of tissue changes, degree of liver fibrosis present, and the regenerative capabilities of the liver cells before developing a more longterm treatment plan or providing you with an outlook for the horse’s recovery.
Diagnosis
Laboratory tests can often detect liver disease before liver failure occurs. Routine biochemical tests such as blood concentrations of liver-specific enzymes are sensitive indicators that liver disease is present, but they do not measure liver function. Additional biochemical tests are available that assess liver function more accurately. These provide the veterinarian with a useful tool for diagnosis.
The horse's history, signs, physical examination findings, and blood test results provide clues that suggest the nature of the liver disease. However, a liver biopsy is the definitive means of diagnosis. Evaluation of the tissue provides valuable information regarding causes and severity of liver disease. Ultrasonography may also be useful to evaluate the size and appearance of the liver or bile duct; gallstones, tumors, abscesses, or other abnormalities. Abdominal x-rays using dyes (called contrast studies) can help diagnose intestinal obstructions and secondary liver disease in foals. Additional specialized tests, such as scintigraphy (a technique in which a radioactive substance is injected into the body and its distribution studied) may be helpful in some cases.
Treatment and Management
The goals for treatment of horses with liver disease or failure are to control hepatic encephalopathy, treat the underlying disease, provide supportive care to allow time for liver regeneration, and prevent injury to the animal and persons working with the animal. Initial treatment of horses with signs of liver disease may be started before the underlying cause and extent of liver damage is known. However, specific therapies for liver disease depend on the causes, the presence of liver failure, whether or not the disease is longterm (chronic), and the degree of liver fibrosis (scarring) or bile duct obstruction.
Treatment is most successful when intervention is early, liver fibrosis is minimal, and there is evidence of regeneration in the liver. Horses with severe fibrosis respond poorly because the potential for regeneration of healthy liver cells is decreased.
For horses with hepatic encephalopathy, sedation may be necessary to prevent injury to the animal or its handlers. Additional therapies may be necessary to reduce the production or absorption of ammonia (a byproduct of protein metabolism that may cause hepatic encephalopathy). If conditions such as dehydration, acid-base and electrolyte (salt) imbalances, or low blood sugar are present, they can be corrected with appropriate intravenous fluids. Adequate fresh water should be available if the horse can swallow normally. Until the nature of the underlying liver disease is known, broad-spectrum antibiotics may be prescribed if a liver infection is suspected. Pain may be controlled with low to moderate doses of nonsteroidal anti-inflammatory drugs. For some horses, certain antioxidants or vitamin supplements may be necessary. Horses with liver disease should be protected from sunlight.
Dietary management is essential for animals with hepatic encephalopathy or liver disease. Affected horses should be fed carefully because difficulty swallowing may be a problem. Follow your veterinarian’s directions as to proper feeding. Normally, a horse with liver disease will need to be fed frequently in relatively small amounts. The recommended diet typically contains easily digestible carbohydrates, provides adequate but not excessive protein, has a high ratio of branched-chain amino acids to aromatic amino acids, and is high in starch. If the horse will not eat voluntarily, feeding by stomach tube or intravenous fluids will be required.
Acute Hepatitis (Short-term Liver Inflammation)
Acute hepatitis is sudden, short-term inflammation of the liver. It can be caused by infections, poisons, or undefined causes. Signs, which include lethargy, jaundice, and poor appetite, may appear suddenly. Sensitivity to light, diarrhea, and blood clotting abnormalities also may be seen. Neurologic signs resulting from low blood sugar and hepatic encephalopathy can be most severe in horses with sudden and severe liver disease. Signs of bacterial blood infection may be present. Loss of appetite can lead to potassium deficiency.
Idiopathic Acute Liver Disease (Serum Sickness, Theiler’s Disease)
Idiopathic acute liver disease, a sudden-onset liver disease with no apparent cause, is the most common cause of acute hepatitis in horses. Approximately 20% of horses with this disorder show signs of liver failure 4 to 10 weeks after receiving a medical product derived from horses, such as tetanus antitoxin. In some cases, the affected horse may not have received the antitoxin but may have been in contact with another horse that did. The disease can also occur in horses that receive equine blood products, such as plasma or serum. In these cases, the condition is sometimes called serum-associated hepatitis or serum sickness. However, horses can develop this disorder with no prior history of exposure to such a product. The cause of the disorder is unknown. Possibilities include a viral disease or an “overreaction” of the horse’s immune system. Lactating mares that receive tetanus antitoxin at foaling seem to be more susceptible.
The onset of signs is usually sudden and may progress rapidly over 2 to 7 days. Death may occur suddenly in 50% to 60% (with an overall death rate as high as 88%) of affected horses. Horses with idiopathic acute liver disease typically show loss of appetite, hepatic encephalopathy (see above), and jaundice. Nervous system signs range from lethargy to aggression or maniacal behavior, blindness, and poor coordination. Light sensitivity, colic, fever, discolored urine, difficulty breathing, weight loss, fluid accumulation under the skin, and bleeding may be seen. Most cases are single, but outbreaks with several horses involved have been reported. If one horse in a group appears ill, the other horses on the same premises should be carefully observed. Most veterinarians will recommend that all the horses receive blood tests for liver disease.
Diagnosis is based on the horse's history, sudden signs, and blood test results. Ultrasonography may also be helpful. A liver biopsy is necessary to confirm the diagnosis.
There is no specific treatment for the disease. Supportive therapy and treatment for the hepatic encephalopathy is often successful. Stressful situations, such as moving the horse or weaning a mare’s foal, may worsen the signs of hepatic encephalopathy and should be avoided, if possible. Recovery depends on the degree of damage in the liver. Your veterinarian can provide insight into the likely outcome. Affected horses that remain stable for 3 to 5 days and that continue to eat often recover. For affected horses that do recover, the longterm outlook is good. In some horses, continued weight loss and death may occur during the months after the initial signs.
Tyzzer Disease
Tyzzer disease is caused by the bacterium Clostridium piliforme. The infection causes a liver infection that destroys liver tissue, inflammation of the heart muscle, and inflammation of the large intestine with diarrhea in foals 1 to 6 weeks old. It is very rare but is usually fatal. The disease often affects apparently healthy, fast-growing foals. It is more common in foals when young, nursing mares are introduced to a farm where the bacterial spores are present or when nursing mares are exposed to lush, high-protein pastures. It is less common in suckling foals on older mares. The disease does not occur in older foals or in adults, although the bacteria may be present in the gut of these animals.
Signs of infection, including depression, fever, jaundice, loss of appetite, and diarrhea, develop quickly and may last a few hours or up to 2 days. Foals often are found dead or in a coma without any preceding signs. Diagnosis is based on the signs and the result of laboratory tests on the blood, feces, or tissues. There is no effective treatment, but supportive care can be attempted.
Once the disease is present on a farm, it may be seen sporadically year after year. However, many foals may be exposed, with only a few (usually those with an impaired immune system) developing the fatal form of the disease. A veterinarian can make recommendations for these facilities to minimize the likelihood of disease.
Cholangiohepatitis
Cholangiohepatitis is inflammation of the bile ducts and adjacent liver, which occasionally causes liver failure in horses. It is sometimes associated with stones in the bile duct, inflammation of the small intestine, intestinal obstructions, tumors, and certain toxins (poisons). Several causes, including bacterial infection in the bile duct, ulcers in the small intestine, decreased intestinal motility, and parasite migration, may cause cholangiohepatitis to develop.
Typically, cholangiohepatitis is a medium- to longterm disease. Affected horses show signs of weight loss, poor appetite, fever, or colic. Jaundice, light sensitivity, and signs of hepatic encephalopathy (see above) may be present. Short-term cholangiohepatitis may occasionally result in severe blood poisoning and death. Diagnosis is confirmed by liver biopsy. Ultrasonography can identify stones in the bile ducts, if present.
If test results indicate a particular type of infection, appropriate antibiotics often produce favorable results. Treatment should be continued for 4 to 6 weeks or longer. Supportive care, such as intravenous fluids or therapy for hepatic encephalopathy, may also be necessary. Liver enzyme tests and biopsies may need to be repeated to determine whether the treatment is successful. If test results are unclear or unavailable, broad-spectrum antibiotics can be prescribed. The outlook is good if fibrosis (scarring) is not severe.
Poisons Affecting the Liver
Hepatotoxins are poisons that damage the liver ( see Table: Substances that can Cause Liver Injury in Horses, below). Fatal liver failure may result if the initial poisoning is severe. More commonly, the liver damage from toxins occurs over a long period of time. The result may be cirrhosis, a condition in which the functional liver tissue is replaced by extensive fibrous tissue. Many hepatotoxins, especially those in plants, have toxic effects on multiple organs, particularly the kidneys, lungs, and digestive tract.
Obtaining a definite diagnosis may be difficult. Careful history, inspection of the environment, laboratory tests, and/or a liver biopsy may be needed to determine the toxic agent. With short-term plant toxicities, remains of toxic plants may be found in the stomach contents.
Specific antidotes for hepatotoxins are limited. Removal of the horses from the source is essential to decrease additional exposure. You may have to change your horse’s pasture or hay or remove toxic plants from the pasture. If the poisoning is recent, your veterinarian may administer laxatives (such as mineral oil or magnesium sulfate) or absorbants (usually activated charcoal or mineral oil) to decrease the absorption of toxic substances. These may not be helpful for longterm toxicity, such as pyrrolizidine alkaloid toxicity caused by plants, in which the toxic agent has been eaten over weeks to months before signs of illness are evident. Care often includes correction of electrolyte (salt), metabolic, and blood sugar disorders through fluid treatment and dietary management. Hepatic encephalopathy (see above) must be controlled. Sunlight should be avoided if light sensitization is present. Antibiotics may be prescribed to prevent skin infection. The outlook for recovery is guarded and depends on the particular toxin.
Gallstones (Biliary Calculi, Choleliths)
Although horses do not have a gallbladder, they can get stones in their bile ducts (biliary stones or calculi). These stones in horses may block bile ducts and cause liver disease, but sometimes they do not cause any signs. Gallstones most commonly affect middle-aged (6- to 15-year-old) horses regardless of sex or breed. One or more stones may be present in the bile ducts. The cause of gallstone formation in horses is not known.
Signs commonly seen in horses with gallstones or bile duct inflammation include weight loss, abdominal pain, jaundice, depression, and fever. Signs of liver failure, including hepatic encephalopathy, clotting abnormalities, and light sensitivity, occur less frequently. These signs often come and go. Complete obstruction of the common bile duct may be accompanied by persistent abdominal pain. Blood tests provide additional evidence for the presence of this disease. Ultrasonography may reveal liver enlargement or the presence of the stones themselves.
Although bile duct obstruction in horses is often fatal, the stones can sometimes be crushed or removed surgically. When stones are small, intravenous fluids and medication may be used to wash out or dissolve the stones. Anti-inflammatory drugs are administered to reduce inflammation and provide pain relief, and antibiotics may be prescribed if infection is likely. Supportive care is provided to manage any liver insufficiency.
Chronic Active Hepatitis
Chronic active hepatitis describes any progressive inflammation within the liver producing sustained, progressive, longterm liver disease. Cholangiohepatitis (see above) can be a part of chronic active hepatitis. The exact cause of this inflammation is not known but may be related to infection, the immune system, or toxins. Many causes acute hepatitis can progress to chronic active hepatitis.
The main signs are weight loss, poor appetite, depression, and lethargy. Jaundice, behavioral changes, diarrhea, light sensitivity, and bleeding are occasionally present. Fever may be persistent or intermittent. Microscopic examination of a liver biopsy is needed for a definite diagnosis. Your veterinarian may also order a tissue culture to check for the presence of bacteria.
Treatment usually includes providing fluids with added potassium chloride, glucose, and vitamin supplementation; dietary management (a low-protein, high branched-chain amino acid, high-carbohydrate diet); and prevention of exposure to the sun if sensitivity is present. Medications may include corticosteroids to reduce inflammation and fibrosis and broad-spectrum antibiotics to treat infection. Other types of drugs may also be necessary. The outlook is fair to good in horses with less severe tissue abnormalities, especially those with a condition that responds well to corticosteroids. The outlook is poor in horses with liver failure, widespread fibrosis (scarring) in the liver, and loss of normal liver cells.
Hyperlipemia and Hepatic Lipidosis
Hyperlipemia is a syndrome in which blood levels of fats (triglycerides, lipids) are increased. Fatty changes in the liver, known as hepatic lipidosis, are another part of the syndrome. Poor feed quality or a decrease in feed intake, particularly during a period of stress or when energy is needed (such as during pregnancy or illness), may result in hyperlipemia syndrome. Hyperlipemia is most commonly seen in the winter and spring.
In this disease, the need for energy triggers excessive movement of fatty acids out of fat tissue, leading to high blood triglyceride levels and eventually to fat accumulation in the liver. Hyperlipemia is seen most commonly in ponies, donkeys, and miniature horses, and less frequently in standard-size adult horses. Affected ponies are commonly obese with a history of recent weight loss due to stress, illness, pregnancy, or early lactation. Hyperlipemia in miniature horses and donkeys frequently develops along with some other illness.
The signs of hyperlipemia include lethargy, weakness, poor appetite, decreased water intake, and diarrhea. Often, there is a history of prolonged loss of appetite, rapid weight loss, and previous obesity. Weight loss, colic, fluid accumulation under the skin, lack of coordination, and trembling may be seen. Impairment of liver function is common; functioning of the kidneys, heart, and skeletal muscles may also be impaired. A diagnosis is often based on the history, signs, and physical examination. High blood triglyceride levels confirm the diagnosis. Cholesterol may also be increased. Laboratory evidence of poor liver function provides additional evidence for this disease.
Correction of the underlying disease, intravenous fluids, and nutritional support are the most essential factors in treatment. Voluntary feeding is preferred if the horse will eat adequate quantities of food; however, supplemental tube feeding may be necessary until feed intake is adequate. For horses that will not eat, intravenous nutrition may be needed. Some horses will also require injection of insulin or heparin. To help prevent hyperlipemia, it is important to ensure that miniature horses and donkeys, ponies, and horses consume adequate amounts of food, especially during periods of stress, illness, or pregnancy.
Death from hyperlipemia is rare in miniature breeds. In most instances, survival depends on the ability to successfully treat the underlying disease. The outlook is often poor in ponies and standard-size horses with hyperlipemia.
Liver Tumors in Horses
Tumors that develop first in the liver are rare in horses. Cholangiocarcinoma is the most common type and is primarily found in middle-aged or older horses. However, tumors that develop in other parts of the body can spread to the liver. Lymphosarcoma is the most common blood cell cancer in horses, and 41% of affected horses will also develop tumors in the liver.
Signs of tumors that originate in the liver include:
lethargy
weight loss
an enlarged abdomen
jaundice
liver failure
Signs of lymphosarcoma vary and may initially include weight loss, decreased appetite, and lethargy. If lymphosarcoma extends throughout the liver, signs of liver failure, jaundice, and severe depression may occur. The diagnosis of liver tumors can be suspected based on blood tests and ultrasonography, but a biopsy is necessary to confirm the diagnosis and determine the type. Your veterinarian will recommend treatment options based on your horse's signs, the type of the tumor, and whether the tumor has spread.
Liver Failure in Foals
Newborn foals may develop liver failure after a severe illness or disease. Conditions that may induce liver failure include blood infections (septicemia), bacterial toxins in the blood (endotoxemia), infectious diseases (such as leptospirosis and equine herpesvirus 1), intestinal obstructions, suffocation during birth, iron toxicity, and malformations of the biliary tract within the liver (called biliary atresia). Stomach ulcers (sores within the lining of stomach) and inflammation in the small intestine can interfere with the flow of bile and cause cholangiohepatitis (inflammation of the bile ducts and surrounding liver tissue, see above). Destruction of the red blood cells (due to neonatal isoerythrolysis or hemolysis) may also cause liver disease. The administration of intravenous nutrition may interfere with the flow of bile and cause liver disease.
Primary Hyperammonemia
Hyperammonemia refers to excessive levels of ammonia (a byproduct of protein metabolism) in the blood. It usually occurs as a result of liver disease, because the liver cannot adequately eliminate ammonia from the blood. Adult horses with primary hyperammonemia have excessive levels of ammonia in the blood but do not have liver disease. The condition causes apparent blindness and severe neurologic signs. The cause is unknown, but it is thought to be due to overgrowth of certain bacteria in the intestines. Although the signs are similar to some types of liver disease, this condition does not appear to be directly related to the liver. The syndrome is nearly always associated with intestinal disease, diarrhea, or colic. In most cases, diarrhea or colic are seen 24 to 48 hours before the neurologic signs. A diagnosis is often based on the signs and results of blood tests that show increased ammonia and glucose levels and low blood bicarbonate levels.
In most horses, neurologic signs resolve within 2 to 3 days with supportive treatment (intravenous fluids, potassium chloride, glucose, sodium bicarbonate) and drugs to reduce the absorption of ammonia.
Hyperammonemia of Morgan Weanlings
A syndrome of ill thrift, increased ammonia levels in the bloodstream, and potential injury to the liver is seen in Morgan foals. Affected foals have been related, but the cause of the syndrome is unknown. Signs are usually first seen around the time of weaning. Liver enzymes (which indicate inflammation of the liver) and blood ammonia levels are increased. Although neurologic disease may improve with treatment, it returns once the treatment is stopped. Unfortunately, the disease is fatal.
Portosystemic Shunts
Portosystemic shunts are conditions in which blood vessels bypass all or part of the liver, causing toxins normally removed by the liver to remain in the blood. This lack of processing causes increased ammonia levels in the blood and nervous system signs.
Although the condition is often present at birth, signs are first seen when affected foals are about 2 months old and start to eat larger amounts of grain and forage. Neurologic signs include staggering, depression, wandering, blindness, circling, and seizures. Signs may be most pronounced and associated with feedings. The shunt can often be seen using imaging techniques such as contrast x‑rays, ultrasonography, or nuclear scintigraphy.
Surgical repair may be attempted in foals in which the site of the shunt can be identified, but the outlook is guarded. Restricting protein intake, carefully managing the diet, and giving products to decrease ammonia production within the intestines may control signs in some foals. Supportive care with fluids, potassium, and dextrose may be needed to help decrease neurologic signs. A high level of care on the part of the owner is required to control this disease over time.
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