Sequential Morphologic and Clinicopathologic Alterations in Dogs with Experimentally Induced Glucocorticoid Hepatopathy

Abstract

SUMMARY Glucocorticoid hepatopathy was induced in 6 Beagle dogs by daily im injections of prednisone (4.4 mg/kg) for 14 consecutive days. Sequential blood samples and percutaneous hepatic biopsy tissues were obtained during this 14 day period and for an additional 42 days. Serum alkaline phosphatase activity was significantly increased by day 2, reached maximum (64-fold increase) by day 20, and decreased gradually to 8-fold above the base-line value by day 56; alanine aminotransferase activity was significantly increased by day 3, reached maximum (10-fold increase) by day 12, and gradually decreased to 3-fold above the base-line value on day 56; and γ-glutamyl transpeptidase activity was significantly increased by day 6, reached maximum (23-fold increase) by day 29, and slowly decreased to 7-fold above the base-line value by the end of the study. Serum leucine aminopeptidase activity and sulfobromophthalein retention remained within the reference interval (for 30 healthy dogs) throughout the study. Serum glucocorticoid concentration reached maximum by day 2 in the treated dogs and slowly decreased throughout the study. Histopathologic evaluation revealed that vacuolar change in hepatocytes was present by day 2, progressed to maximum severity between days 5 and 14, and gradually decreased in severity, but remained present throughout the study. The hepatocellular vacuolation changed from a diffuse distribution to centrilobular as the study progressed. Glycogen content of hepatocytes steadily increased during the period of prednisone administration, reached maximum amount on day 15, and slowly decreased, but was still increased at the end of the study. The distribution of glycogen accumulation progressed from diffuse to periportal during the study. Clinical signs of Cushing's syndrome developed by day 7 and included decreased hair growth, polyphagia, polydipsia, polyuria, mild lethargy, and semisolid feces. Necropsies on day 56 revealed slightly swollen, pale, and friable liver in 2 of 5 treated dogs (1 dog had died on day 14) and catarrhal enteritis in the 6 treated dogs. Atrophy of the adrenal gland zona fasciculata was observed microscopically in treated dogs. Gross and microscopic alterations were absent in other organs. This study demonstrates the rapid appearance and prolonged persistence of clinical, morphologic, and clinicopathologic alterations in dogs with experimentally induced glucocorticoid hepatopathy. The findings will be useful in the diagnosis and prognosis of naturally occurring glucocorticoid hepatopathy and chemotherapeutic hepatopathy.