Many older dogs with alkaline phosphatase (ALP) elevations often have what is referred to as vacuolar hepatopathy (VH). Vacuolar hepatopathy basically refers to hepatocytes with vacuoles in their cytosol that may contain glycogen, fat, intracellular water, or other metabolic wastes. A liver histology report may read, "diffuse hepatic vacuolar change suggestive of steroid hepatopathy—check for Cushing's syndrome or a history of chronic glucocorticoid administration."

Dogs with VH secondary to exogenous glucocorticoid administration or elevated endogenous glucocorticoid concentrations typically have hepatomegaly and other relevant clinical signs such as polyphagia, polyuria, polydipsia, cutaneous changes and susceptibility to infection. Affected dogs usually have high serum alkaline phosphatase (ALP) and g-glutamyltransferase activities as well as high serum concentrations of haptoglobin and cholesterol.

While glucocorticoid treatment or spontaneous hyperadrenocorticism (HAC) are routinely implicated as the underlying cause in dogs with histologically confirmed VH, many investigators have observed that these vacuolar changes are not specific for glucocorticoid excess. For example, other disorders such as IBD, pancreatitis, nodular hyperplasia, and non-hepatic neoplasia have been associated with VH.

Objective and Methodology
The objective of this recent study was to characterize disorders associated with VH in dogs, evaluate any hepatic and clinicopathologic morphologic abnormalities, and determine their affiliation with an excess of steroidogenic hormone. There were 336 dogs with histologically confirmed moderate or severe VH. The medical records of these dogs were assessed and the dogs were grouped by underlying disorder, glucocorticoid exposure, acinar zonal distribution of lesions, and histologic severity.

Among the dogs studied, 12 disease groups (neoplastic, acquired hepatobiliary, neurologic, immune-mediated, gastrointestinal tract, renal, infectious, cardiac disease, diabetes mellitus, portosystemic vascular anomaly, adrenal gland dysfunction, and miscellaneous disorders) were identified. Of the 336 dogs, 186 (55%) dogs had evidence of glucocorticoid exposure, whereas the remaining 150 (45%) dogs had none. Acinar zonal distribution of hepatic vacuolation and clinicopathologic values did not differ between dogs with and without evidence of glucocorticoid exposure. Steroidogenic hormone exposure often caused a 3-fold increase in the likelihood of severe VH. Of 226 dogs with high serum ALP activity, 102 (45%) had no evidence of glucocorticoid exposure.

Conclusions and Clinical Relevance
Results of this study suggested that neoplasia and congenital or acquired hepatobiliary disease are common in dogs with VH. These findings support an association between VH, high ALP activity, and illness-invoked physiologic stress. Histologic confirmation of VH should initiate a diagnostic search for a primary disease if glucocorticoid treatment and HAC are ruled out.

Reference: Sepesy et al, JAVMA 229:246-252, 2006; Rogers, JAVMA 229:918, 2006; Center et al, JAVMA 229:918-919, 2006.