Phenotypic Analysis of Hepatic T Lymphocytes in a Dog with Chronic Hepatitis

Abstract

ABSTRACT. We evaluated hepatic T lymphocyte phenotypes in a dog with chronic hepatitis. Before treatment, numerous CD3+ lymphocytes were demonstrated in the liver, and the ratio of CD4+/CD8+ was remarkably high (2.96; reference range, 0.33 ± 0.12). After treatment, CD3+ lymphocyte infiltration in the liver was reduced, and the ratio of CD4+/CD8+ decreased to 0.31. Therefore, hepatic T lymphocytes, especially CD4+ lymphocytes, might play a central role in the pathogenesis of this dog with chronic hepatitis. KEY WORDS: canine chronic hepatitis, lymphocyte, phenotype.J. Vet. Med. Sci. 68(11): 1219-1221, 2006 Chronic hepatitis, a common liver disease in dogs, is histologically characterized by lymphocyte infiltration in the liver [2]. The most numerous infiltrated cells are CD3+ T lymphocytes as determined by immunohistochemistry [1], but their exact phenotype, such as CD4 or CD8 has not been investigated. Furthermore, changes in lymphocyte infiltration in canine chronic hepatitis have not been analyzed before and after corticosteroid therapy, which is an effective therapy for the disease [5]. This report describes phenotypes of T lymphocytes in the liver of a dog with chronic hepatitis before and after treatment.A 4-year-old female English cocker spaniel was referred to the Nihon University Animal Medical Center with anorexia and elevated liver enzyme levels that had persisted for more than three months. Physical examination revealed no abnormalities. Complete blood counts were unremarkable, but blood chemistry revealed that alanine aminotransferase (ALT 528 U/l, reference range 10 to 100 U/l), aspartate aminotransferase (AST 145 U/l, reference range 0 to 50 U/l), and alkaline phosphatase (ALP 310 U/l, reference range 23 to 212 U/l) were elevated. Serum bile acid levels were remarkably increased (fasting SBA, 14.1 µmol/l; postprandial SBA, 193.0 µmol/l; reference range, 0 to 25 µmol/l), and blood coagulation screening tests revealed abnormalities (PT, 11.2 sec; reference range, 6.0 to 8.5 sec; APTT, 24.2 sec; reference range, 12.0 to 18.0 sec, fibrinogen, 64 mg/dl; reference range, 200 to 400 mg/dl; antithrombin III, 57%; reference range, 85 to 150%). Abdominal radiography and ultrasonography showed splenohepatomegaly. Laparoscopy revealed that liver was enlarged and that its surface was rough and its edges were rounded. Wedge liver biopsy was performed with an ultrasonically activated scalpel (Harmonic Scalpel, Ethicon Endo-Surgery, Cincinnati,

American Cocker Spaniel Chronic Hepatitis in Japan

“…Corticosteroids were used in all cases. It is uncertain if this may have influenced their survival considerably, although the possible beneficial effect of this drug on Cocker Spaniel hepatitis has been reported , . Corticosteroids have been reported to have a direct or indirect (ie, via suppression of the inflammation) antifibrotic effect .…”

ACVIM consensus statement on the diagnosis and treatment of chronic hepatitis in dogs

“…Specific criteria for the diagnosis of immune‐mediated hepatitis in dogs have not been developed. An immune basis in some dogs with idiopathic CH is suggested by several criteria (Table ) which include the presence of lymphocytic infiltrates in the liver, abnormal expression of major histocompatibility complex class II proteins, positive serum autoantibodies, familial history of liver disease, association with other immune‐mediated disorders, female predisposition, and favorable response to immunosuppression . A presumptive clinical diagnosis of immune‐mediated CH in the dog requires elimination of other etiologies and a favorable response to immunosuppressive treatment.…”

“…The overall mean age when clinical signs are reported is 7.2 years (11 studies, n = 983 dogs). Disease duration before diagnosis is unclear . Reported age ranges in specific breeds are shown in Supporting Information Table S1.…”

“…An immune basis in some dogs with idiopathic CH is suggested by several criteria (Table 5) which include the presence of lymphocytic infiltrates in the liver, abnormal expression of major histocompatibility complex class II proteins, positive serum autoantibodies, familial history of liver disease, association with other immune-mediated disorders, female predisposition, and favorable response to immunosuppression. 1,7,9,14,15,20,32,34,[146][147][148][149][150][151][152][153][154][155][156][157][158][159][160][161][162][163]165,167,168 A presumptive clinical diagnosis of immune-mediated CH in the dog requires elimination of other etiologies and a favorable response to immunosuppressive treatment. Currently, the lack of commercially available tests to detect liver-specific antibody-antigen interactions or cell immunosensitization in dogs with CH limits the definitive determination of an immune-mediated etiology.…”

Chronic hepatitis in man and in dog: a comparative update

“…The correlation between chronic hepatitis and an immune-mediated process has also been suggested in a study in which in the liver of a dog affected by chronic hepatitis was found an increased ratio of CD4+/CD8+ lymphocytes (33), and in a study in dogs with chronic hepatitis showing proliferation of peripheral blood mononuclear cells in response to liver membrane antigens (34). Furthermore, a study performed on Dobermans affected by hepatitis at different clinical stages, showed upregulation of MHC class II antigens in hepatocytes, leading the authors to hypothesize an autoimmune ground (35), similarly to another study in which for Doberman hepatitis, showing an association between the disease and the homozygous haplotype DLA-DRB1*00601/DQA1*00401/DQB1*01303, it has been hypothesized an immune origin (36).…”