25 Mar Hepatitis in Dogs
Just as in humans, hepatitis in dogs can result from a variety of causes, often unknown or only suspected. Indeed the term hepatitis’ is a generic term used to describe an inflammatory disease of the liver, which can be either acute or chronic (i.e. > 6 months), without specification of the cause.
The liver is the chemical laboratory of the body in dogs, as well as in all other species, and its proper functioning is essential for several important processes such as: carbohydrate, lipid and protein metabolism; fat digestion; detoxification of the body from waste metabolites, drugs and toxins; storage of vitamins, glycogen, fat, iron and other trace metals; synthesis of blood and coagulation proteins; immunoregulation. Any disease affecting the liver, including hepatitis, can negatively impact these varied functions. The liver, however, has great functional reserve as well as a remarkable regenerative capacity. This means that hepatic cells in a previously rest state or even new hepatic cells can replace the function of damaged or dead cells. As a result, the appearance of relatively specific signs of hepatic disease and dysfunction occurs only late in the disease progression, after liver’s functional reserves have been exhausted.
Signs of Hepatitis in Dogs
Early clinical signs of hepatic inflammation (both acute and chronic) are usually aspecific and mimic those observed in other organ systems. They are typically referable to the gastrointestinal system (diarrhea, anorexia and vomiting) and renal system (increased urination with resulting increased thirst), and can lead to a relatively severe dehydration state. As already said, specific signs of hepatic dysfunction appear late in the disease progression. They include : icterus, a yellow discoloration of the mucous membranes associated with the accumulation of a waste metabolite called bilirubin; hypoglycemia, caused by glycogen depletion or failure of glucose synthesis; bleeding tendencies, associated with a failure in the synthesis of coagulation proteins; abdominal enlargement, due to liver enlargement (hepatomegalia) or ascites (accumulation of fluid in the abdominal cavity); and hepatic encephalopathy, a neurological condition associated with failure of the liver to detoxify neurotoxins generated in the intestinal tract.
Acute hepatitis in dogs is often referred as ‘idiopathic’, which means that the cause of hepatitis is not known in most cases. However, in analogy to many other species, viruses may be the cause, while bacterial infection almost never causes acute hepatitis in dogs. In acute hepatitis the functional reserve of the liver is almost always preserved and usually recovery takes place spontaneously in about three weeks without specific treatment. Supportive treatment may be however indicated in case of severe vomiting (antiemetic therapy) or dehydration (fluid therapy).
The most serious concern about acute hepatitis in dogs is the fact that it can progress into chronic hepatitis which, if not treated at an early stage, can progress into liver fibrosis and cirrhosis. Therefore, whenever acute hepatitis is diagnosed in dogs, it is important that the veterinarian take a control liver biopsy 4-5 weeks after the diagnosis, in order to discover whether the acute form is turning into the chronic form and start treating chronic hepatitis in an early phase.’
Chronic hepatitis in dogs, also called inflammatory canine hepatic disease, refers to a syndrome in which death of hepatic cells (hepatocellular necrosis) has occurred and is associated with a chronic inflammatory process which typically progresses to liver fibrosis (replacement of hepatic tissue with fibrous tissue) and cirrhosis (progressive derangement of the liver architecture and function). Chronic hepatitis in dogs may have various causes, including drugs (acetaminophen), mushroom toxins (phalloidine), metals (copper), infectious agents (leptospirosis). However in most cases it is not possible to indicate a specific cause and’ the condition is referred as chronic idiopathic hepatitis, in which a immune-mediated mechanism is supposed, at least in part, to be involved in the pathogenesis. A breed predisposition to chronic hepatitis and hepatic fibrosis and cirrhosis also exists. Breeds that have been reported to have an increased frequency of chronic hepatitis include in particular Doberman pinschers (particularly middle-aged, female individuals), and Bedlington terriers, West Highland White terriers and dalmatians, which are prone to copper-related hepatitis. An important pathogenetic mechanism involved in chronic hepatitis (regardless of its cause) is the so called oxidative damage, resulting from the liberation of oxygen free radicals from inflammatory and immune cells during the inflammatory process. Oxygen free radicals are toxic for cells, since they cause damage to cell membranes surrounding living cells as well as their nucleus and other inner organelles, eventually leading to cell death. This explains why antioxidants play a crucial role in the prevention and treatment of liver chronic inflammation.
Treating Chronic Hepatitis
Treatment of chronic hepatitis in dogs partly depends on the cause, when known. The treatment of first choice for chronic idiopathic hepatitis (where the involvement of an autoimmune mechanism is suspected) is steroid therapy, namely with prednisolone. Corticosteroids have in fact anti-inflammatory effects but also antifibrotic effects, so they can help fight inflammation as well as prevent hepatic fibrosis. However glucocorticoids have also many unwanted side effects and are contraindicated when an infectious cause is known, since these drugs act by inhibiting the immune response which can help overcome the infection (at least in the first stages of chronic hepatitis). A safer alternative to glucocorticoids is UDCA (ursodeoxycholic acid), which is one of the natural bile acids produced in the liver and secreted with the bile into the small intestine to aid in fat digestion. It has been suggested that UDCA has a positive effect on liver function through different mechanisms: it prevent hepatic cells from entering the apoptosis pathway, enhances the bile flow and efflux of toxins accumulated in the liver, modulates the immune system reducing the immune response and finally increases the production of glutathione (GSH) and metallothionein which play an important role in preventing oxidative damage. In chronic hepatitis caused by copper accumulation in the liver, chelating therapy is indicated: copper chelators such as D-penicillamine act by binding free extracellular copper and promoting its excretion into the urine by the kidneys. As already said, antioxidant therapy may play an important role in the treatment of almost all forms of chronic hepatitis by preventing liver oxidative damage. The main antioxidants used in the treatment of liver diseases are vitamin C, vitamin E, silymarin (the active ingredient extracted from the fruit of milk thistle or Silybum marianum) and S-adenosyl-L-methionine (SAMe). In addition, UDCA has antioxidant properties as well.
Dietary management of chronic hepatitis in dogs is also important. For example a low-sodium diet may help to control ascites, a low copper diet is indicated in case of copper-associated hepatitis, while a diet with reduced content of aromatic amino acids and integrated with lactulose and soluble fiber may be beneficial in managing hepatic encephalopathy. Well-balanced commercial diets aimed at supporting liver function are available, that meet the proper requirements of energy content, reduction of aromatic amino acids, presence of soluble fiber and low content of copper and sodium.
To sum up, there exists no universal therapy for chronic hepatitis in dogs. Treatment depends on the cause of liver inflammation and must be individualized and made accordingly to each patient’s needs. What is important is to intervene as early as possible, in order to prevent total liver dysfunction and its life-threatening consequences.