E475
Liver Disease

Introduction: In order to understand diseases of the liver, it is important to have some knowledge of the normal function of this complicated organ. The liver is important in keeping the body’s metabolism and function in balance. It has been estimated that the liver is responsible for over 1,500 essential processes on a biochemical level. The failure of any of these biochemical functions could lead to death of the animal.

Some of the main functions of the liver include proper handling of carbohydrates (sugars, starches), lipids (fats, cholesterol, bile acids), and proteins. Some of the important proteins produced by the liver include blood clotting factors, urea (used by the kidney to help with the body’s water preservation), and albumin (the main protein in the blood which helps maintain the proper fluid volume in the heart and blood vessels). Essential vitamins and minerals are produced, stored, or altered by the liver for proper use in the body. The liver aids in the functions of the immune system, the endocrine system, and in maintaining healthy blood cells.

One very important function of the liver is its role as the body’s filter from the digestive tract. The entire digestive tract contains bacteria and food in various stages of breakdown. Nutrients are absorbed into the blood through tiny capillaries from the stomach and intestines. Blood from the digestive tract may be thought of as "dirty," since it is so close to a source of contamination— millions of bacteria and possibly harmful substances taken into the body through the mouth. From here, the blood enters the liver’s portal blood system, a second bed of capillaries where the liver can "detoxify" any harmful substances and acts as the first line of defense against invading bacteria from the digestive tract. This function of the liver as a filter from the stomach and intestines becomes very important later in the understanding of many diseases of the liver.

A specific condition called hepatic encephalopathy (HE) often develops with diseases in which the liver’s function as a filter fails. "Hepatic encephalopathy" actually means disease of the brain associated with the liver. HE occurs when toxic by-products, usually filtered by the liver, arrive at high levels in the brain via the bloodstream. These by-products of digestion, especially ammonia, cause hallucination-like symptoms to occur in the brain along with circling or pacing, aggression, blindness that seems to come and go, "head pressing" (standing with the head lowered and pressed into a corner or against a wall), and hepatic comas. Horses have also been known to yawn excessively.

The liver has a tremendous ability for regeneration and functional reserve. It is able to tolerate injury and insult better than most organs without failing (although sickness may be very apparent in the body) and can repair itself remarkably well following damage. These are wonderful features of this vital organ, but can also make it difficult to recognize when a serious disease of the liver is present.

 

Introduction: Liver disease occurs when the liver becomes inflamed (called hepatitis) or inured in some way. Liver disease can be the result of a one time event or can be the result of continued injury or inflammation over an extended period of time. Liver failure occurs when approximately 75% of the liver tissue becomes damaged over time or is damaged at one time. This amount of damage exceeds the liver’s functional reserve and leads to clinical signs of liver failure.

Causative Agents: Some of the possible causes of liver disease include the following:

1. Hepatitis (Theiler’s disease, Serum hepatitis): This problem occurs in adult horses that are given tetanus antitoxin. Theiler’s disease is most often seen in mares that are given tetanus antitoxin 1-3 months after foaling. This is probably the most common cause of acute liver problems (hepatitis) in adult horses.
2. The administration or consumption of toxic drugs or poisons:
   1. Since the liver is the first organ to handle any drug taken orally, an overdose of many drugs can cause liver failure. Some drugs which have been known to cause acute liver failure include inhaled anesthetic gases, some anticonvulsants, tetracycline, and trimethoprim-sulfa antibiotics.
   2. Poisonous substances and plants can also damage the liver. Some of these include pyrrolizidine-alkaloid containing plants, blue-green algae, aflatoxin, moldy alfalfa, and heavy metals (iron, copper).
3. Infectious agents: Viral diseases are suspected to be responsible for sudden failure of the liver. Bacterial infections are probably more common than any other type of infectious cause of sudden liver failure. The most common type of bacterial caused liver failure occurs when overwhelming loads of bacteria from the digestive tract enter the liver. This often happens with a sudden injury to the intestines or when overgrowth of aggressive types of bacteria occurs.

Clinical Signs: Clinical signs of liver disease are usually dramatic, but often not specific. Jaundice or icterus (a yellowness to the gums and white of the eye) is often present in horses. Signs of hepatic encephalopathy (discussed previously) are often noticed and may be profound, with severe depression and disorientation. Other signs that are sometimes seen include dehydration, weight loss, diarrhea, ascites (fluid buildup under the skin), pruritus (itching), and photosensitization. In the most severe cases, the animal may experience hemophilia (bleeding tendencies due to a loss of blood-clotting ability). Widespread damage to the liver that is not immediately life-threatening may lead to chronic liver failure if there remains too little healthy tissue to regenerate.

Diagnosis: Diagnosis of liver disease is accomplished with a variety of tests. Physical examination by a veterinarian followed by routine CBC, serum chemistry panel, and urinalysis are generally performed first. An increase in the liver enzymes gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) often indicate a liver problem. Serum bile acid and bilirubin testing is generally recommended with any liver disease. For a complete diagnosis to be made, a liver biopsy (often guided by ultrasound) is obtained and examined by a veterinary pathologist.

Treatment: Treatment of liver disease centers around aggressive supportive care and eliminating the cause of the failure, if possible. Discontinuing any drug which has potentially caused the liver to fail is essential. Fluid therapy and slow correction of the blood acid-base balance and dissolved salt levels (sodium, potassium, chloride) must be initiated as soon as possible. If hepatic encephalopathy is present, this concern must be specifically treated by reducing ammonia levels in the bloodstream. Laxatives (mineral oil), lactulose, and oral medications can be given to help reduce ammonia levels in the blood. Antibiotics (neomycin and metronidazole) are selected specifically for their ability to remove ammonia-producing bacteria from the colon. Diet therapy is started as soon as possible. Diets that are restricted in proteins are very important in recovery and are usually fed initially in small amounts, several times daily. Treatment may continue for weeks to months, and can even be indefinite in some cases in order to prevent recurrence of the liver failure. An example of a low protein diet that can be fed would include *one part beet pulp with one-quarter to one-half part cracked corn mixed with molasses. This should be fed 4-6 times a day. Oat hay, grass hay, or sorghum can replace the beet pulp when necessary. Animals that will not eat must be force fed. Depending on the cause of the liver failure, additional treatments are sometimes utilized. These would include the use of antibiotics (ceftifur, penicillin, trimethoprim-sulfa), vitamin B, folic acid, and vitamin K.

*Example diet taken from Smith, Bradford P. Large Animal Internal Medicine. St. Louis: Mosby 1996: 949.

Prognosis: Prognosis for recovery depends on how severe the injury to the liver has been, on the ability to remove any contributing cause of the disease, and on the general health of the animal. Older horses in poor body condition may experience failure of multiple organs together with a relatively moderate injury to the liver; whereas, a younger horse in good health that experiences the same injury to the liver may be able to fully recover with proper treatment. Generally speaking, if the horse is not eating, continues to be in constant acidosis, or does not respond to initial treatments, the prognosis is poor.

 

Clinical Signs/Diagnosis: One of the most startling findings with this disease is that many foals are found dead, without any previous signs of disease. When clinical signs are present, they include lethargy (depression), fever, and jaundice, going off feed, diarrhea, and seizures. Unfortunately, since there is no test to diagnose this disease in live foals, a definitive (positive) diagnosis of Tyzzer’s disease can be made only on post-mortem examination. Post-mortem examination of the liver often reveals that it is swollen and has areas of hemorrhage and necrosis. Microscopically, the bacteria can be seen inside of the liver cells at the edges of the necrotic areas.

Disease Transmission: The manner by which Tyzzer’s disease is spread from foal to foal is not fully known. It is believed that the most likely means of spreading the disease is by ingesting fecal matter contaminated with the Tyzzer’s disease bacteria. The disease is not considered to be highly contagious between animals; however, foals that are born on farms where previous cases have been diagnosed should be watched carefully for the first 7 weeks of life.

Treatment: Due to the severity and seriousness of the disease, most foals die. In fact, some studies conclude that no reported cases of confirmed Tyzzer’s disease have been successfully treated. If a case of Tyzzer’s disease is detected early on, treatment may include shock doses of intravenous (IV) fluids and glucose. Intranasal oxygen, anticonvulsants, and broad-spectrum antibiotics (penicillin, gentamicin, or metronidazole) should also be given.

 

Introduction: This liver condition occurs when horses consume plants that contain pyrrolizidine alkaloid (PA). The effects of PA toxicity are cumulative, meaning that the toxic dose of the plants do not have to be consumed at one time to cause liver damage. Some animals suffer liver damage or even death after consuming one large dose of PA, while others will continue to consume small, but damaging amounts of PA until a "threshold" has been met and clinical signs of problems result.

Clinical Signs: The signs noticed with pyrrolizidine alkaloid (PA) toxicity are associated directly with the damage it causes in the liver. For example, jaundice or icterus (a yellowness to the gums and white of the eye) is often present and signs of hepatic encephalopathy (discussed previously) can be seen. Other signs that are sometimes noticed include dehydration, weight loss, diarrhea, ascites (fluid buildup under the skin), pruritus (itching), and photosensitization. Signs of PA toxicity will sometimes not show up until a year after the horse has stopped eating the problem plant(s).

Diagnosis: Suspected cases of pyrrolizidine alkaloid (PA) toxicity can be identified when elevated liver enzymes are detected in a blood sample. Serum bile acid and bilirubin levels are also elevated. A liver biopsy is one of the best ways of determining if PA toxicity is the cause. If the animal has already died because of PAs, necropsy findings will also help to determine the cause. At necropsy, the liver is small, firm, and pale brown to yellow. Samples of the horse’s feed can also be analyzed for the presence of PA containing plants.

Treatment: The treatment options for liver disease associated with pyrrolizidine alkaloid (PA) toxicity depends on the severity of the liver damage. If the horse has been consuming significant amounts of PAs over a period of time and has significantly damaged the liver to the point of fibrosis, treatment is not beneficial. However, if the liver is only mildly irritated or damaged, the liver can repair itself and return to a relatively normal state. A detailed description of the treatment options for liver disease can be found in the previous information.

Here is a list of some of the plants that are known to cause pyrrolizidine alkaloid toxicity: