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Canine Vacuolar Hepatopathy

By

Sharon A. Center

, BS, DVM, DACVIM, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University

Last full review/revision May 2015 | Content last modified May 2015

Vacuolar hepatopathy (VH) is a commonly diagnosed canine liver syndrome in which hepatocytes become markedly distended with cytosolic glycogen with or without discrete membrane-bound lipid inclusions. Glycogen-like VH is associated with typical or atypical hyperadrenocorticism or endogenous release of corticosteroids in response to chronic stress, illness, inflammation, or neoplasia. Liver biopsy is often pursued because of unexplained increases in serum ALP activity. Transaminase activity may be only modestly increased; GGT may or may not be increased.

Abdominal radiography may reveal hepatomegaly or changes associated with an underlying disease process. Metastatic disease or mineralized airways (chronic hyperadrenocorticism) may be seen on thoracic radiography. Ultrasonography reveals subjective hepatomegaly and hypoechoic hepatic nodules against a hyperechoic parenchymal background, the so-called “Swiss cheese pattern” that cannot be differentiated from infiltrative mass lesions, hepatic fibrosis, nodular hyperplasia, regenerative nodules, or cirrhosis. In some cases, grossly evident hepatic nodules cannot be discerned by ultrasound examination. VH usually is the underlying hepatic lesion in dogs with idiopathic nodular hyperplasia and also is common in dogs with hepatic adenomas, hepatocellular carcinoma, and gallbladder mucoceles. Progressive VH merges into the classic hepatic syndrome associated with the hepatocutaneous lesion (see Hepatocutaneous Syndrome in Small Animals). Hepatic biopsy is needed for definitive diagnosis, because glycogen-vacuolated hepatocytes are also seen in necroinflammatory liver disorders. Intrahepatic extramedullary hematopoiesis is common.

It is critical to determine and treat any underlying disease process. Careful scrutiny for adverse drug reactions is also necessary, with a focus on drugs associated with “induction phenomenon.” These should be discontinued and replaced with an alternative therapy. Clinicians should investigate any use of holistic or herbal remedies that may have systemic glucocorticoid or adrenocorticotropic hormone (ACTH) effects.

Nutritional support is important and must be individualized. In most cases, a normal protein intake is appropriate. VH in dogs with hyperlipidemia requires treatment with a fat-restricted diet (<2 g fat/100 kcal of diet). A protein-restricted diet should not be fed, unless indicated (eg, demonstration of HE or ammonium biurate crystalluria). In fact, protein restriction may augment development of this liver lesion, especially if it is associated with hypoaminoacidemia as in the hepatocutaneous syndrome. A supplemental water-soluble vitamin is recommended for all dogs. Antioxidants should be provided, because some experimental evidence implicates oxidative injury in degenerative VH. Ursodeoxycholic acid is recommended if TSBA concentrations are increased.

Vacuolar Hepatopathy in Scottish Terriers:

VH associated with a progressive increase in ALP activity is common in Scottish Terriers. Studies suggest this syndrome is linked with a breed-related abnormality involving adrenal steroidogenesis, leading to overproduction of progestins and androgens. Severe progressive VH is first noted in middle-aged dogs and can be either slowly progressive or progress rapidly over a few years to liver failure, cirrhosis, APSSs, ascites, and hyperbilirubinemia. Ultrasonographic imaging discloses the typical "Swiss cheese" pattern of VH (described above). High risk of hepatocellular carcinoma is recognized in dogs demonstrating progressive hepatic remodeling. Liver biopsy often discloses dysplastic proliferative lesions antecedent to formation of hepatocellular carcinoma. Adrenomegaly is common and may be bilateral or unilateral. Treatment with adrenal-modulating drugs can be hazardous and appears ineffective. Supportive care as for dogs with declining hepatic function, monitoring both sequential biochemical profiles for sudden marked increases in ALP or ALT activity that may signal tumor formation, and serial ultrasonographic evaluations for enlarging hepatic mass lesions are recommended. Early surgical excision of enlarging hepatic mass lesions that likely represent hepatocellular carcinomas is recommended to allow complete excision. A subset of dogs studied also have copper-associated liver injury that cannot be inferred on the basis of biochemical assessments but rather require liver biopsy for definitive diagnosis.

OTHER TOPICS IN THIS CHAPTER

Hepatic Disease in Small Animals
Overview of Hepatic Disease in Small Animals
Hematology in Hepatic Disease in Small Animals
Coagulation Tests in Hepatic Disease in Small Animals
Enzyme Activity in Hepatic Disease in Small Animals
Other Serum Biochemical Measures in Hepatic Disease in Small Animals
Hepatic Function Tests in Small Animals
Imaging in Hepatic Disease in Small Animals
Cholecystocentesis in Hepatic Disease in Small Animals
Liver Cytology in Small Animals
Liver Biopsy in Small Animals
Pathologic Changes in Bile in Small Animals
Nutrition in Hepatic Disease in Small Animals
Fulminant Hepatic Failure in Small Animals
Hepatic Encephalopathy in Small Animals
Portal Hypertension and Ascites in Small Animals
Portosystemic Vascular Malformations in Small Animals
Acquired Portosystemic Shunts in Small Animals
Other Hepatic Vascular Disorders in Small Animals
Hepatotoxins in Small Animals
Infectious Diseases of the Liver in Small Animals
Feline Hepatic Lipidosis
Biliary Cirrhosis in Small Animals
Canine Cholangiohepatitis
Canine Chronic Hepatitis
Lobular Dissecting Hepatitis in Small Animals
Canine Vacuolar Hepatopathy
Metabolic Diseases Affecting the Liver in Small Animals
Hepatocutaneous Syndrome in Small Animals
Nodular Hyperplasia in Small Animals
Hepatic Neoplasia in Small Animals
Miscellaneous Liver Diseases in Small Animals
Diseases of the Gallbladder and Extrahepatic Biliary System in Small Animals
Cholecystitis in Small Animals
Canine Gallbladder Mucocele
Other Disorders of the Gallbladder in Small Animals
Other Disorders of the Bile Ducts in Small Animals
Extrahepatic Bile Duct Obstruction in Small Animals
Cholelithiasis in Small Animals
Biliary Tree Rupture and Bile Peritonitis in Small Animals
Feline Cholangitis/Cholangiohepatitis Syndrome
Hepatobiliary Fluke Infection in Small Animals
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