Retrospective evaluation of cyclosporine in the treatment of presumed idiopathic chronic hepatitis in dogs

Abstract

Background The etiology of idiopathic chronic hepatitis (ICH) in dogs is poorly understood, but evidence supports an immune‐mediated pathogenesis in some dogs. Objectives To describe a case series of dogs with presumed ICH treated with cyclosporine (CsA) with or without concurrent medications and to document the incidence of biochemical remission and factors associated with failure to attain remission. Animals Forty‐eight client‐owned dogs diagnosed with presumed ICH, treatment of which included CsA. Methods Two‐institution, retrospective case series of dogs between 2010 and 2017. All dogs were treated with CsA with or without concurrent medications for ≥2 weeks. Data were collected from medical records. Results Biochemical remission (<1.1 times the upper limit of normal for alanine aminotransferase activity) was attained in 79% of dogs (38/48). Median dose of CsA at remission was 7.9 mg/kg/d (range, 2.5‐12.7 mg/kg/d) and median time to remission was 2.5 months (range, 0.75‐18 months). Concurrent hepatoprotectant treatment was not associated with likelihood of remission. Clinical score, ascites, hypoalbuminemia, hyperbilirubinemia, prolonged coagulation times, dose, and duration of treatment were not associated with the probability of remission or time to remission. Common adverse effects of CsA were gastrointestinal signs in 38% (18/48) and gingival hyperplasia in 25% (12/48) of treated dogs. Conclusion and Clinical Importance A treatment regimen including CsA and frequent hepatoprotectant use resulted in biochemical remission of ICH in most dogs. None of the evaluated factors, including hepatoprotectant use, were significantly associated with likelihood of remission. Future prospective studies are indicated to evaluate CsA monotherapy in ICH dogs.

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

“…A few studies using prednisolone, azathioprine, or cyclosporine in CH have been reported in dogs and are summarized in Table 20. 146,[162][163][164][165][166]334 In these reports, some dogs with CH showed improvement, inferring an immunomodulatory or anti-inflammatory benefit. However, it is difficult to draw general conclusions from these studies because they were done in many different breeds, used variable doses of immunosuppressive therapies with other concurrent therapies, often lacked post-treatment histology, and involvement of Cu was not standardized or quantified.…”

“…A few studies using prednisolone, azathioprine, or cyclosporine in CH have been reported in dogs and are summarized in Table . In these reports, some dogs with CH showed improvement, inferring an immunomodulatory or anti‐inflammatory benefit.…”

Demographic and histopathologic features of dogs with abnormally high concentrations of hepatic copper

“…27,30,31,84 However, in dogs, it is unclear whether analogous disease processes lead to higher Cu burden. Dogs diagnosed with idiopathic chronic hepatitis 4,89 or biliary diseases often have normal hepatic Cu. 32,46 Although 1 study found decreased biliary excretion of Cu in Dobermans with copper associated hepatitis, 90 a separate study found that chronic extrahepatic bile duct obstruction did not increase hepatic Cu until dogs were administered supplemental Cu intravenously.…”

Characterization of clinical presentation, histological features, ultrasonographic findings, and survival in 29 dogs with granulomatous hepatitis

“…Other exclusion criteria were a diagnosis of cancer, recent exposure (within 1 month) to hepatotoxic drugs or supplements known to elicit a granulomatous response, or hepatic copper concentrations >1000 μg/g dry weight with documented response to hepatic copper chelation treatment. Dogs with increased hepatic copper concentrations that failed to respond to adequate chelation treatment, defined as persistently increased liver transaminase activities, were included in the study because these cases were at least in part considered to have clinically relevant GH in conjunction with copper hepatopathy 16,17 …”