Chronic hepatitis that does not focus on biliary structures is more common in dogs than cats. Although there is an identifiable etiology for some categories of chronic hepatitis, in most cases the cause remains unidentified. Increased hepatocellular copper and Kupffer cell iron stores are common in dogs with chronic hepatitis. The degree of metal accumulation and its acinar location help determine its relevance to tissue injury.
Other associated conditions include infectious canine hepatitis, chronic hepatitis secondary to infectious processes, and chronic exposure limiting factors and lesson plans xenobiotics including certain drugs, oral zinc and canine skin allergies, biologic toxins, and chemicals.
Terminology that reflects specific etiology or breed predilection, such as drug-associated chronic hepatitis, infectious chronic hepatitis, copper-associated hepatitis, etc, is preferred. The fibromas and topamax idiopathic chronic hepatitis indicates that an etiology has not been determined.
Histopathologic changes are generally similar in all cases of chronic hepatitis, regardless of the underlying cause, and include a lymphocytic-plasmacytic inflammation with infiltrates extending into hepatic parenchyma, variable single cell or piecemeal necrosis, and in advanced disease, development of bridging fibrosis and nodular regeneration.
The acinar zone of involvement varies with the underlying cause. Copper-associated hepatopathy is a leading cause of chronic hepatitis in dogs, increasing in prevalence since when copper supplements in commercial dog foods were modified to a more bioavailable form. Retrospective evaluation of liver biopsies from Labrador Retrievers and Doberman Pinschers from to indicated that dogs of these breeds, with and without chronic hepatitis, had significantly higher hepatic copper concentrations in the last 10 yr of the study.
Management of body copper homeostasis relies on numerous copper transporters, chaperones, oral zinc and canine skin allergies, and binding proteins, as well as biliary canalicular egress. Copper-associated hepatopathy is best characterized in Bedlington Terriers, which have a mutation deletion of exon 2 of the COMMD1 copper transporter protein.
Careful breeding programs guided by liver biopsy and genetic testing PCR gene mutation test have remarkably reduced disease frequency in Bedlington Terriers. However, some Bedlington Terriers with biopsy-confirmed copper-associated hepatopathy lack this specific gene mutation. Failure to excrete copper into bile leads to chronic hepatitis and, eventually, cirrhosis and liver failure. Affected dogs develop high liver copper concentrations by 1 yr of age normal: Liver injury is reflected by increased ALT activity and has been shown in dogs with hepatic copper as low as ppm.
Oral zinc and canine skin allergies disease phases were historically characterized in Bedlington Terriers. Acute hepatic necrosis occurred in dogs Genetic testing is recommended for selection of Bedlington Terrier breeding stock. However, definitive diagnosis of copper-associated hepatopathy requires liver biopsy in adult dogs with qualitative copper stains reconciled with quantitative copper measurements. Many other purebred and mixed-breed dogs of all ages also may develop copper-associated hepatopathy.
More commonly and perhaps oral zinc and canine skin allergies severely affected are Labrador Retrievers; whether the high breed popularity influences this observation remains unclear. Doberman Pinschers, West Highland White Terriers, oral zinc and canine skin allergies, and some dogs related to Dalmatians also may develop profoundly increased hepatic copper concentrations accompanied by severe liver injury.
A genetic cause has not been identified in any of these breeds. It is important to emphasize that copper-associated hepatopathy can be the primary cause of hepatitis in any dog purebred or mixed breed and can be definitively diagnosed only by liver biopsy.
There is no recognized gender predisposition. Histologic features of copper-associated hepatopathy include a focus on the centrilobular region zone 3finding eosinophilic granules within the french and indian war fort plans compartment of hepatocytes and within macrophages in areas of single cell necrosis. Small granulomas develop subsequent to hepatocyte necrosis and release of copper granules into the surrounding parenchyma.
Zone 3 lesional—associated parenchymal collapse is verified with reticulin staining centrilobular collapse and fibrillar collagen deposition with Masson oral zinc and canine skin allergies staining centrilobular connective tissue deposition. With advanced injury, regenerative nodules and regions of parenchymal extinction are seen.
The prominent role of copper in driving tissue injury is verified by finding copper granules rhodanine staining in nearly every hepatocyte within regenerative nodules.
Treatment of copper-associated hepatopathy requires copper chelation with concurrent restriction of copper intake from oral zinc and canine skin allergies and water sources. Dietary copper restriction can be achieved by feeding a prescription diet formulated for dogs with HE delivering 2, oral zinc and canine skin allergies.
These low-protein formulas can be supplemented with protein sources low in copper to raise the dietary protein intake to 3. Supplementary protein sources are selected using the USDA food tables sort based on copper concentrationwith feeding amounts of selected foods calculated using the Nutritional Analysis Tool 2. Copper in water should contain Administration of antioxidants is important, because copper induces liver damage through oxidative injury.
Thereafter, chronic therapy may be instituted by reducing the d - penicillamine dosage by half and administering the drug every other day while maintaining dietary copper restriction.
Alternatively, the dog may be treated with zinc acetate see below. Caution is warranted with trientine used at the originally higher recommended dose, because this has induced acute renal failure in dogs with severe copper storage hepatopathy.
An alternative approach to manage copper storage hepatopathy is daily administration of oral zinc acetate, gluconate, sulfate to inhibit copper uptake from the GI tract zinc induces enterocyte metallotheinine, oral zinc and canine skin allergies, which irreversibly binds copper and prohibits its absorption; copper is subsequently eliminated with effete enterocytes in feces.
Although zinc treatment theoretically increases dietary options, study of oral zinc and canine skin allergies efficacy of zinc treatment in people with Wilson disease confirms unreliable control of dietary copper uptake. Zinc therapy must not be given concurrent with chelation therapy, oral zinc and canine skin allergies, because this will thwart efficacy of each treatment.
Oral zinc is not well tolerated by some dogs, commonly causing vomiting, nausea, and inappetence. Vitamin C is contraindicated in copper storage hepatopathy, because it may foster injurious transition metal effects.
After chelation therapy, it is essential to continue to limit copper ingestion in food and water lifelong. Adherence to a copper-restricted diet and water source may obviate the need for continual chelation or zinc therapy. Although West Highland White Terriers have been shown to accumulate excessive hepatic housing and residential plan, not all dogs with high hepatic copper concentrations develop hepatitis.
Some dogs with severely increased hepatic copper concentrations die of old age without necroinflammatory liver lesions. Although West Highland White Oral zinc and canine skin allergies with chronic hepatitis usually do have high tissue copper concentrations, they differ from Bedlington Terriers with copper storage hepatopathy in that: Focal hepatitis may be seen in asymptomatic young adult dogs.
Chronic hepatitis is associated with anorexia, nausea, vomiting, oral zinc and canine skin allergies, jaundice, and later ascites. Increased liver enzymes develop first with focal disease, followed by increased TSBA concentrations and then hyperbilirubinemia as the severity of liver injury advances.
Histopathologic changes include multifocal necroinflammatory hepatitis with typical copper-affiliated granulomas and single cell necrosis, with advanced disease culminating in cirrhosis. Treatments target copper primarily if an association between inflammation and copper accumulation is histologically verified.
For treatment recommendations, see copper-associated hepatitis, oral zinc and canine skin allergies, Copper-associated Hepatopathyand canine chronic hepatitis, Canine Chronic Hepatitis. Idiopathic chronic hepatitis is defined as chronic necroinflammatory self-perpetuating liver disease associated with a nonsuppurative inflammatory infiltrate.
To qualify as an idiopathic syndrome, an underlying cause should have been rigorously pursued yet not discovered. Autoimmune hepatitis is included in this classification. An antinuclear antibody test, testing for endemic infectious diseases titer or antigen testsand investigation of drug and toxin exposure, along with dietary, environmental, and family history, must be undertaken. Middle-aged to older adult dogs are more commonly affected; there are no breed or gender predilections.
With advancing disease, increased TSBA concentrations are followed by hyperbilirubinemia. Other findings may include a nonregenerative anemia, leukocytosis, and hyperglobulinemia. At this stage, overt signs of HE may manifest. In early disease, liver oral zinc and canine skin allergies is normal and there may be no demonstrable ultrasonographic lesions. In late-stage disease, radiographs may demonstrate a small liver with nodular lesions detected on ultrasound examination. Ultrasonographic evaluations also may disclose ascites and APSSs in dogs with advanced liver injury.
Chronic, sustained, unexplained increases in liver enzymes usually indicate liver biopsy. Biopsy specimens should be submitted for both aerobic and anaerobic bacterial cultures and quantification of copper, iron, and zinc. Copper stains must be reconciled with quantitative copper measurements to avoid erroneous interpretations.
Liver biopsies must be large enough to detail at least 15 contiguous portal triads, and biopsies must be taken from several different liver lobes. Supportive care nutritional, vitamin supplementation and use of specific therapies to slow inflammation and fibroplasia and to restore liver antioxidant status are recommended.
Antibiotics are initially prescribed empirically until results of the biopsy and tissue cultures become available, and then adjusted or discontinued based on culture results. Immunosuppressive drugs are used only after careful consideration and exclusion of infectious or toxic causes and when an active disease process nonsuppurative or pyogranulomatous inflammation is characterized on liver biopsy. In the presence of ascites or APSSs, dexamethasone is used instead of prednisone or prednisolonebecause it is a synthetic glucocorticoid lacking mineralocorticoid effects.
The dose is adjusted considering its longer biologic half-life 72—96 hrs and higher potency 7—10 fold more than prednisolone or prednisone such that dexamethasone is used at 0. An immunomodulatory agent additional to the glucocorticoid is used to enable titration of the glucocorticoid dosage to the lowest effective dose.
This reduces the dose of each immunosuppressive drug, reducing their adverse effects and achieving a multimodal immunosuppressive effect.
Adverse effects of glucocorticoids in chronic hepatobiliary disease include sodium and water retention which can exacerbate or promote ascitescatabolic effects which can promote HEGI ulceration and enteric bleeding which can precipitate HEpancreatitis, predisposition to secondary infections, glucose intolerance, and iatrogenic hyperadrenocorticism glycogen-like VH. Beneficial effects may not be seen for up to 8 wk. Because azathioprine can cause bone marrow suppression and gastroenteric, pancreatic, and rarely liver toxicity, frequent follow-up assessments are imperative.
If bone marrow toxicity is identified only after chronic administration monthsazathioprine should be permanently discontinued. Pancreatitis and idiopathic hepatotoxicity are rare adverse effects that also mandate drug discontinuation. Mycophenolate mofetil is used in dogs that cannot tolerate azathioprine or, alternatively, as an initial immunosuppressant.
Cyclosporin is another alternative immunosuppressant used in combination therapy. Some dogs previously managed well on azathioprine have lost remission on conversion to cyclosporin.
Other dogs started on cyclosporin as their primary immunosuppressant have responded well. In the absence of placebo-controlled clinical trials for treatment of canine immune-mediated hepatitis, treatment is individualized to each dog based on sequential monitoring and, sometimes, follow-up liver biopsy.
Discontinuation of immunosuppressive therapy is not recommended in oral zinc and canine skin allergies with chronic hepatitis; if drugs are discontinued, they should be withdrawn gradually, with close monitoring serum biochemical profiles.
Because complete remission is difficult to evaluate clinically, a follow-up biopsy may be required. In most cases, serum ALT activity serves as a surrogate marker of disease activity. Prognosis is widely variable. Dogs with ascites require dietary sodium restriction and treatment with furosemide and spironolactone see Portal Hypertension and Ascites in Small Animals.
Dogs with HE require dietary protein modification and may benefit from lactulose and administration of low-dose metronidazole. If immune-mediated hepatitis is considered the definitive diagnosis, careful consideration should be given before administration of routine vaccinations.
Nonspecific immune stimulation may adversely stimulate hepatitis and cause disease flare. This popular breed is predisposed to chronic hepatitis that is commonly associated with pathologic accumulation of hepatocellular copper see copper-associated paxil and low sex drive, Copper-associated Hepatopathy.
However, this breed also can develop a primary lymphoplasmacytic hepatitis that appears to involve immune-mediated mechanisms. Ultrasonographic imaging often demonstrates hypoechoic and hyperechoic parenchymal nodules, subjective microhepatica, and less frequently, irregular liver margins and ascites.