Serial evaluation of liver enzyme activities in dogs with pulmonary coccidioidomycosis administered per os fluconazole

Pulmonary coccidioidomycosis is a relatively common fungal disorder in dogs that have lived in or traveled to endemic regions and fluconazole is a common antifungal treatment. Liver enzymopathy can occur with fluconazole administration, but the frequency of occurrence nor potentially associative factors have been explored in dogs with pulmonary coccidioidomycosis. Therefore, our objectives were to describe the occurrence and magnitude of liver enzyme activity (LEA) elevation in dogs with pulmonary coccidioidomycosis during treatment with per os fluconazole and identify variables associated with liver enzymopathy. This was a retrospective observational study that analyzed serum biochemical data obtained from a separate prospective study that included 32 client-owned dogs with newly diagnosed pulmonary coccidioidomycosis from October 2020 to February 2021. Per os fluconazole administration (median dosage: 16.2 mg/kg/day) was initiated after diagnosis and dogs were evaluated once every 3 months thereafter until remission or for a maximum of 12 months. Recorded biochemical parameters at each visit (including baseline) included alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT). Magnitude of increased LEA was based on the fold increase above the upper limit of the reference interval and defined as mild (10×). Forty-seven percent (15/32) of dogs were documented to have elevations in one or more LEAs after initiation of fluconazole administration during the study period. Thirty-four percent and 25% of dogs had elevated ALP and ALT activities, respectively, at some point during treatment. Elevations in AST and GGT activities were rare. The magnitude of LEA elevation was mild in all cases. Logistic regression models did not identify associations between age, weight, sex, neutered status, prednisone administration, fluconazole dose or duration of treatment with the occurrence of liver enzymopathy. Approximately half of dogs with pulmonary coccidioidomycosis are expected to develop mild increases in activities of ALP and/or ALT with rare involvement of AST or GGT at some point during treatment with fluconazole up to 12 months.