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Educational Note
Treating Canine Liver Disease Though canine liver disease can be life threatening, it also can be managed successfully when diagnosed early. Proper nutrition and medication both can contribute to successful management of dogs with liver disease. "Treatment of liver disease requires knowing the exact cause of disease or extent of liver damage," says David C. Twedt,D.V.M., professor of small animal medicine at Colorado State University's College of Veterinary Medicine and Biomedical Sciences. "Early identification and appropriate therapy are very important." Early diagnosis can be challenging, since the liver has a tremendous reserve capacity and will continue, to function adequately until damage occurs to about 70 percent of the organ. Although it does make diagnosis difficult, the liver's reserve capacity is important, since the liver is responsible for many critical body functions ranging from producing key proteins to protecting the body from toxic substances. Liver disease generally is suspected based on clinical signs noted during a physical examination, says Susan E. Bunch, D.V.M., Ph.D, professor of internal medicine at the College of Veterinary Medicine at North Carolina State University. "Many veterinarians offer wellness examinations, and if abnormal liver enzyme activities are identified, they are investigated." "Proper nutrition can help improve liver function and enhance the liver's functional reserve," says Purina Research Fellow Dorothy Laflamme, D.V.M., Ph.D. "Nutrition also helps support liver regeneration and aids symptomatic relief of clinical signs." Liver Function Understanding how liver disease can impact canine health requires learning more about how the liver functions, Among its many roles, the liver is responsible for producing proteins, including transport proteins, coagulation and anticoagulation proteins, and albumin, the protein principally responsible for maintaining fluid and blood pressure in the veins of the body. The liver also helps to maintain the body's blood glucose, or sugar, concentration; aids in digestion of nutrients, such as fat; and activates and deactivates drugs in the body. The liver, stores life-sustaining amounts of blood and certain vitamins and minerals. And, through a well-developed network of immune cells and antibodies, the liver protects the body from infectious agents absorbed from the intestine. Signs of Disease Clinical signs of liver disease in dogs include jaundice, abdominal fluid, and abnormalities in liver size or shape. Signs of disease detectable to owners might include lethargy, depression, poor appetite, weight loss, vomiting, diarrhea, increased drinking and urination, and reduced exercise tolerance. More severe cases might include central nervous system abnormalities such as excessive salivation, pacing, seizures or coma. Predisposed Breeds A number of dog breeds are suspected of having a genetic basis for increased incidence of chronic hepatitis, or ongoing liver disease. For example, 20 breeds of dogs are recognized as having abnormal copper concentrations in conjunction with liver disease. Among these, Bedlington terriers have an inherited autosomal recessive gene that causes copper toxicosis, a disease depicted by a toxic accumulation of copper in the liver. Awareness of breed predisposition is important for disease diagnosis and breeding considerations. Diagnosing Liver Disease "The two most common liver abnormalities identified in dogs are secondary reactive disorders and primary liver disease," Twedt says, "Reactive disorders are very common and occur secondary to systemic or metabolic disease, with the liver as the innocent bystander. Secondary disorders generally resolve when the primary disease is treated. Primary liver diseases, on the other hand, are those in which the liver is solely responsible for the disorder." Because the liver is central to many other organs, it can suffer consequences from illness in other organs. For example, Bunch says, dogs with inflammatory bowel disease can have modest increases in blood liver enzyme activities as a result of absorbing toxic substances from q diseased intestine. Due to the proximity of the pancreas to the bile duct, severe pancreatitis can cause transient bile duct obstruction and dramatic changes in liver function tests. A liver biopsy in both cases would indicate results related to intestinal or pancreatic disease. Laboratory testing often is needed to confirm the presence of liver disease and to help characterize the type. Unexplained liver enzyme activities that are persistently abnormal should be investigated using radiographs, ultrasound and possibly liver biopsy. For most types of primary liver disease, biopsy is essential, Twedt says. For dogs with chronic hepatitis, repeat liver biopsy is an ideal way to determine whether medications are working. Careful consideration should be given when deciding whether to take a liver biopsy. "Indications for performing a liver biopsy are a patient with abnormal liver enzymes and clinical evidence of liver disease," Twedt says. "A biopsy can help explain the cause of abnormal liver enzymes or function tests, such as blood bile acids." The cause of primary liver diseases, such as acute liver injury and chronic hepatitis, can range widely. "Among causes of primary liver disease are reactions to certain antibiotics, toxic injury from plants, insects, environmental poisons, copper accumulation, various drugs and infectious causes" Bunch says. "Many times the cause is unknown." Acute liver failure occurs when there has been a sudden massive loss of normal liver tissue and function, potentially resulting in death before therapeutic intervention can occur. At the other end of the scale, abnormalities in blood levels of liver enzymes can be found during routine evaluation, yet with no other clinical evidence of disease." Diet Management "Dietary management is an important part of treatment for dogs with liver disease," Bunch says. "Depending on the type and severity of liver disease, a special diet may or may not be needed. The purpose of a special diet would be to aid in addressing liver dysfunction caused by an inability to process protein waste products, such as ammonia, which cause central nervous system abnormalities, and to provide an appropriate blend of nutrients designed to promote liver recovery." In most cases, dogs should be fed a quality complete and balanced diet, which is important to support liver regeneration and healing. Home-prepared diets may not contain complete nutrition, and thus, long-term usage is discouraged, Laflamme says. Adequate protein and caloric intake is important, because it supports liver repair and recovery. Frequent, small meals should be fed to limit time between meals and to improve nutritional status, and a highly digestible diet also is important. While no single diet will suit the nutritional and clinical needs of all dogs with liver disease, selection of an appropriate diet depends on specific clinical signs. For dogs that show signs of mental disturbances secondary to liver failure, or hepatic encephalopathy, the protein content of the diet should be decreased. Even in these dogs, however, protein is necessary to help the liver regenerate and to help maintain lean body mass. The source of protein is important in dogs with liver disease. Dogs have fewer signs of end-stage liver disease when protein comes from milk or vegetable diets as opposed to meat diets. "Meat and blood are poorly tolerated in encephalopathic, patients," Laflamme "The main thing is to monitor protein adequacy to assure protein depletion does not occur." In dogs such as Bedlington terriers that accumulate copper in the liver, copper should be controlled, and diets should be supplemented with appropriate vitamins, Twedt says. Though diets low in copper will not reduce existing copper in the liver, they may help to slow further copper accumulation. Copper chelating agents also may be necessary. Dietary fiber also is believed to benefit dogs with liver disease by helping to acidify contents in the colon and minimize ammonia absorption. Dietary fiber binds bile acids in the intestinal tract and promotes their removal, thus altering the bile acid pool. Soluble fiber may help to manage end-stage liver disease by impairing intestinal uptake of ammonia. In addition, dietary fat from medium-chain triglycerides may be useful in some patients with liver disease. "Medium-chain fats are more easily digested and absorbed, and provide a readily available source of energy," Laflamme says. Disease Management With early intervention, therapeutic management of canine liver disease can be beneficial. Anti-inflammatory therapy, for example, can help reduce inflammation caused by chronic hepatitis. "One study we conducted at Colorado State showed that dogs with chronic hepatitis tended to have prolonged survival when treated with anti-inflammatory drugs," Twedt says. Antioxidant therapy helps to control free radicals produced in chronic hepatitis. Free radicals are molecules with an unpaired electron that are created from toxic agents or certain drugs and we believed to cause liver damage during fat peroxidation. Antioxidants help minimize oxidative damage by scavenging free radicals. Vitamin E functions as an antioxidant by protecting membrane phospholipids from oxidative damage when free radicals are formed. Therapy with vitamin E helps to reduce oxidative injury to liver tissue by providing protection. Vitamin E also helps protect the liver from copper related oxidant damage. Copper chelators can be used to help reduce high levels of copper in the liver, such as Bedlington terriers experience with copper toxicosis. Chelators bind with copper either in the blood or tissue and then facilitate its removal through the kidneys. In addition, zinc therapy helps to prevent copper accumulation in dogs with abnormal liver copper. Dietary zinc binds to an intestinal copper-binding protein called metallothionein, preventing its transfer into the blood. The metallothionein-bound copper is later excreted in the stool. Long-Term Prognosis Early identification of liver disease, combined with appropriate therapy and diet, are key to successful management. If the basic structure of the liver, including, its anatomic and physiologic relationships, is preserved, complete recovery is highly likely due to the liver's tremendous regenerative capacity. Though there is no specific recommendation for preventing disease, early diagnosis has been shown to improve survival. Potential Causes of Primary Liver Disease in Dogs Plants: Cycad Palm, especially the seeds; Chinaberry tree fruit; Aflatoxins; Amanita mushrooms Insects: Bees; wasps; hornets Environmental Poisons: Closantel; heavy metals, including lead, arsenic and thallium Drugs: Trimethoprim-sulfas; carprofen; acetaminophen; phenobarbital; primidone; Tetracycline; Diethylcarbamazine-exibendazole
Information provided by Susan E Bunch, D.V.M., Ph.D., Professor of Internal Medicine at the College of Veterinary Medicine at North Carolina State University. Breeds Associated with Increased Liver Copper Concentrations
Bedlington Terrier*
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