• 1.

    Rogers WA, Ruebner BH. A retrospective study of probable glucocorticoid-induced hepatopathy in dogs. J Am Vet Med Assoc 1977;170:603606.

    • Search Google Scholar
    • Export Citation
  • 2.

    Badylak SF, Van Vleet JF. Sequential morphologic and clinicopathologic alterations in dogs with experimentally induced glucocorticoid hepatopathy. Am J Vet Res 1981;42:13101318.

    • Search Google Scholar
    • Export Citation
  • 3.

    Badylak SF, Van Vleet JF. Tissue gamma glutamyl transpeptidase activity and hepatic ultrastructural alterations in dogs with experimentally induced glucocorticoid hepatopathy. Am J Vet Res 1982;43:649655.

    • Search Google Scholar
    • Export Citation
  • 4.

    Sanecki RK, Hoffmann WE & Gelberg HB, et al. Subcellular location of corticosteroid-induced alkaline phosphatase in the canine hepatocytes. Vet Pathol 1987;24:296301.

    • Search Google Scholar
    • Export Citation
  • 5.

    Dillon AR, Spano JS, Powers BD. Prednisolone induced hematologic, biochemical, and histological changes in the dog. JAm Anim Hosp Assoc 1980;16:831837.

    • Search Google Scholar
    • Export Citation
  • 6.

    Fittschen C, Bellamy EC. Prednisone-induced morphologic and chemical changes in the liver of dogs. Vet Pathol 1984;21:399406.

  • 7.

    Rutgers HC, Batt RM & Vaillant C, et al. Subcellular pathologic features of glucocorticoid-induced hepatopathy in dogs. Am J Vet Res 1995;56:898907.

    • Search Google Scholar
    • Export Citation
  • 8.

    Dillon AR, Sorjonen DC & Powers RD, et al. Effects of dexamethasone and surgical hypotension on hepatic morphologic features and enzymes in dogs. Am J Vet Res 1983;44:19961999.

    • Search Google Scholar
    • Export Citation
  • 9.

    Center SA, Warner KL & McCabe J, et al. Evaluation of the influence of S-adenosylmethionine on systemic and hepatic effects of prednisolone in dogs. Am J Vet Res 2005;66:330341.

    • Search Google Scholar
    • Export Citation
  • 10.

    Center SA. Hepatic lipidosis, glucocorticoid hepatopathy, vacuolar hepatopathy, storage disorders, amyloidosis, and iron toxicity. In: Guilford WG, Center SA & Strombeck DR, et al., eds. Strombeck's small animal gastroenterology. 3rd ed. Philadelphia: WB Saunders Co, 1996;766801.

    • Search Google Scholar
    • Export Citation
  • 11.

    Solter PF, Hoffmann WE & Chambers MD, et al. Hepatic total 3 alpha-hydroxy bile acids concentration and enzyme activities in prednisone treated dogs. Am J Vet Res 1994;55:10861092.

    • Search Google Scholar
    • Export Citation
  • 12.

    Center SA, Slater MR & Manwarren BS, et al. Diagnostic efficacy of serum alkaline phosphatase with gamma-glutamyltransferase in dogs with histologically confirmed hepatobiliary disease: 270 cases (1980–1990). J Am Vet Med Assoc 1992;201:12581264.

    • Search Google Scholar
    • Export Citation
  • 13.

    Wellman ML, Hoffmann WE & Dorner JL, et al. Comparison of the steroid-induced, intestinal, and hepatic isoenzymes of alkaline phosphatase in the dog. Am J Vet Res 1982;43:12041207.

    • Search Google Scholar
    • Export Citation
  • 14.

    Hadley SP, Hoffmann WE & Kuhlenschmidt MS, et al. Effect of glucocorticoids on alkaline phosphatase, alanine aminotransferase, and gamma-glutamyltransferase in cultured dog hepatocytes. Enzyme 1990;43:8998.

    • Search Google Scholar
    • Export Citation
  • 15.

    Sanecki RK, Hoffmann WE & Gelberg HB, et al. Subcellular location of corticosteroid-induced alkaline phosphatase in canine hepatocytes. Vet Pathol 1987;24:296301.

    • Search Google Scholar
    • Export Citation
  • 16.

    Sanecki RK, Hoffmann WE & Dorner JL, et al. Purification and comparison of corticosteroid-induced and intestinal isoenzymes of alkaline phosphatase in dogs. Am J Vet Res 1990;51:19641968.

    • Search Google Scholar
    • Export Citation
  • 17.

    Teske E, Rothuizen J & DeBruune JJ, et al. Corticosteroidinduced alkaline phosphatase isoenzyme in the diagnosis of canine hypercorticism. Vet Rec 1989;125:1214.

    • Search Google Scholar
    • Export Citation
  • 18.

    Jensen AL, Poulsen JSD. Preliminary experience with the diagnostic value of the canine corticosteroid induced alkaline phosphatase isoenzyme in hypercorticism and diabetes mellitus. Zentralbl Veterinarmed [A] 1992;39:342348.

    • Search Google Scholar
    • Export Citation
  • 19.

    Wilson SM, Feldman EC. Diagnostic value of the steroidinduced isoenzyme of alkaline phosphatase in the dog. J Am Anim Hosp Assoc 1992;28:245250.

    • Search Google Scholar
    • Export Citation
  • 20.

    Solter PF, Hoffmann WE & Hungerford LL, et al. Assessment of corticosteroid-induced alkaline phosphatase isoenzyme as a screening test for hyperadrenocorticism in dogs. J Am Vet Med Assoc 1993;203:534538.

    • Search Google Scholar
    • Export Citation
  • 21.

    Geiger TL, Feldman EC & Wallack ST, et al. Lymphoma as a model for chronic illness: effects on adrenocortical function testing. J Vet Intern Med 2003;17:154157.

    • Search Google Scholar
    • Export Citation
  • 22.

    Wiedemann AL, Charney SC & Barger AM, et al. Assessment of corticosteroid-induced alkaline phosphatase as a prognostic indicatory in canine lymphoma. J Small Anim Pract 2005;46:185190.

    • Search Google Scholar
    • Export Citation
  • 23.

    Kaplan AJ, Peterson ME, Kemppainen RJ. Effects of disease on the results of diagnostic tests for use in detecting hyperadrenocorticism in dogs. J Am Vet Med Assoc 1995;207:445451.

    • Search Google Scholar
    • Export Citation
  • 24.

    Chastain CB, Franklin RT & Ganjam VK, et al. Evaluation of the hypothalamic pituitary-adrenal axis in clinically stressed dogs. J Am Anim Hosp Assoc 1986;22:435442.

    • Search Google Scholar
    • Export Citation
  • 25.

    Center SA, Leveille CA & Baldwin BH, et al. Direct spectrometric determination of serum bile acids in the dog and cat. Am J Vet Res 1984;45:20432050.

    • Search Google Scholar
    • Export Citation
  • 26.

    Center SA, ManWarren T & Slater MR, et al. Evaluation of twelve-hour preprandial and two-hour postprandial serum bile acids concentrations for diagnosis of hepatobiliary disease in dogs. JAm Vet Med Assoc 1991;199:217226.

    • Search Google Scholar
    • Export Citation
  • 27.

    Frank LA, Schmeitzel LP, Oliver JW. Steroidogenic response of adrenal tissues after administration of ACTH to dogs with hypercortisolemia. J Am Vet Med Assoc 2001;218:214216.

    • Search Google Scholar
    • Export Citation
  • 28.

    Chambon P. The nuclear receptor superfamily: a personal retrospect on the first two decades. Mol Endocrinol 2005;19:14181428.

  • 29.

    Bollen M, Keppens S, Stalmans W. Specific features of glycogen metabolism in the liver. Biochem J 1998;336:1931.

  • 30.

    Wiedmeyer CE, Solter PE, Hoffmann WE. Kinetics of mRNA expression of alkaline phosphatase isoenzymes in hepatic tissues from glucocorticoid-treated dogs. Am J Vet Res 2002;63:10891095.

    • Search Google Scholar
    • Export Citation
  • 31.

    Prittie JE, Barton LJ & Peterson ME, et al. Pituitary ACTH and adrenocortical secretion in critically ill dogs. J Am Vet Med Assoc 2002;220:615619.

    • Search Google Scholar
    • Export Citation
  • 32.

    Behrend EN, Kemppainen RJ & Boozer AL, et al. Serum 17-α-hydroxyprogesterone and corticosterone concentrations in dogs with nonadrenal neoplasia and dogs with suspected hyperadrenocorticism. J Am Vet Med Assoc 2005;227:17621767.

    • Search Google Scholar
    • Export Citation
  • 33.

    Strombeck DR. Clinicopathologic features of primary and metastatic neoplastic disease of the liver in dogs. J Am Vet Med Assoc 1978;173:267269.

    • Search Google Scholar
    • Export Citation
  • 34.

    Sterczer A, Meyer HP & Van Sluijs FJ, et al. Fast resolution of hypercortisolism in dogs with portosystemic encephalopathy after surgical shunt closure. Res Vet Sci 1999;66:6367.

    • Search Google Scholar
    • Export Citation
  • 35.

    Meyer HP, Rothuizen J. Increased free cortisol in plasma of dogs with portosystemic encephalopathy (PSE). Domest Anim Endocrinol 1994;11:317322.

    • Search Google Scholar
    • Export Citation
  • 36.

    Roth L. Comparison of liver cytology and biopsy diagnoses in dogs and cats: 56 cases. Vet Clin Pathol 2001;30:3538.

  • 37.

    Cole TL, Center SA & Flood SN, et al. Diagnostic comparison of needle and wedge biopsy specimens of the liver in dogs and cats. J Am Vet Med Assoc 2002;220:14831490.

    • Search Google Scholar
    • Export Citation
  • 38.

    Wang KY, Panciera DL & Al-Rukibat RK, et al. Accuracy of ultrasound-guided fine-needle aspiration of the liver and cytologic findings in dogs and cats: 97 cases (1990–2000). J Am Vet Med Assoc 2004;224:7578.

    • Search Google Scholar
    • Export Citation
  • 39.

    Roberts SM, Lavach JD & Macy DW, et al. Effect of ophthalmic prednisolone acetate on the canine adrenal gland and hepatic function. Am J Vet Res 1984;45:17111713.

    • Search Google Scholar
    • Export Citation
  • 40.

    Moore GE, Mahaffey EA, Hoenig M. Hematologic and serum biochemical effects of long-term administration of antiinflammatory doses of prednisone in dogs. Am J Vet Res 1992;53:10331037.

    • Search Google Scholar
    • Export Citation
  • 41.

    Glaze MB, Crawford MA & Nachreiner RF, et al. Ophthalmic corticosteroid therapy: systemic effects in the dog. J Am Vet Med Assoc 1988;192:7375.

    • Search Google Scholar
    • Export Citation
  • 42.

    Meyer DJ, Moriello KA & Feder BM, et al. Effect of otic medications containing glucocorticoids on liver function test results in healthy dogs. J Am Vet Med Assoc 1990;196:743744.

    • Search Google Scholar
    • Export Citation

Advertisement

Vacuolar hepatopathy in dogs: 336 cases (1993–2005)

Lisa M. Sepesy DVM, DACVIM1, Sharon A. Center DVM, DACVIM2, John F. Randolph DVM, DACVIM3, Karen L. Warner4, and Hollis N. Erb DVM, PhD5
View More View Less
  • 1 Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 2 Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 3 Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 4 Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 5 Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.

Abstract

Objective—To determine disorders associated with vacuolar hepatopathy (VH), morphologic hepatic and clinicopathologic abnormalities, and affiliation with steroidogenic hormone excess in dogs.

Design—Retrospective case series.

Animals—336 dogs with histologically confirmed moderate or severe VH.

Procedures—Information on signalment, results of diagnostic testing, definitive diagnoses, and exposure to glucocorticoids (ie, exogenous glucocorticoid administration or high endogenous concentrations of steroidogenic hormones) was obtained from medical records. Dogs were grouped by underlying disorder, glucocorticoid exposure, acinar zonal distribution of lesions, and histologic severity.

Results—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. There were 186 (55%) dogs with and 150 (45%) dogs without evidence of glucocorticoid exposure. Acinar zonal distribution of hepatic vacuolation and clinicopathologic values did not differ between dogs with and without evidence of glucocorticoid exposure. However, a 3-fold increased likelihood of severe VH was associated with steroidogenic hormone exposure. Of 226 dogs with high serum alkaline phosphatase activity, 102 (45%) had no evidence of glucocorticoid exposure.

Conclusions and Clinical Relevance—Results suggest that neoplasia and congenital or acquired hepatobiliary disease are common in dogs with VH and provide support for the suggestion that VH, high alkaline phosphatase activity, and illness-invoked physiologic stress may be associated. Histologic confirmation of VH should initiate a diagnostic search for a primary disease if glucocorticoid treatment and hyperadrenocorticism are ruled out.

Abstract

Objective—To determine disorders associated with vacuolar hepatopathy (VH), morphologic hepatic and clinicopathologic abnormalities, and affiliation with steroidogenic hormone excess in dogs.

Design—Retrospective case series.

Animals—336 dogs with histologically confirmed moderate or severe VH.

Procedures—Information on signalment, results of diagnostic testing, definitive diagnoses, and exposure to glucocorticoids (ie, exogenous glucocorticoid administration or high endogenous concentrations of steroidogenic hormones) was obtained from medical records. Dogs were grouped by underlying disorder, glucocorticoid exposure, acinar zonal distribution of lesions, and histologic severity.

Results—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. There were 186 (55%) dogs with and 150 (45%) dogs without evidence of glucocorticoid exposure. Acinar zonal distribution of hepatic vacuolation and clinicopathologic values did not differ between dogs with and without evidence of glucocorticoid exposure. However, a 3-fold increased likelihood of severe VH was associated with steroidogenic hormone exposure. Of 226 dogs with high serum alkaline phosphatase activity, 102 (45%) had no evidence of glucocorticoid exposure.

Conclusions and Clinical Relevance—Results suggest that neoplasia and congenital or acquired hepatobiliary disease are common in dogs with VH and provide support for the suggestion that VH, high alkaline phosphatase activity, and illness-invoked physiologic stress may be associated. Histologic confirmation of VH should initiate a diagnostic search for a primary disease if glucocorticoid treatment and hyperadrenocorticism are ruled out.

Contributor Notes

Dr. Sepesy's present address is Department of Clinical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.

Address correspondence to Dr. Center.