Canine Vacuolar Hepatopathy
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.
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.