Incidence, timing, and risk factors of azathioprine hepatotoxicosis in dogs

Abstract

Background: The use of azathioprine (AZA) in dogs is limited by the development of hepatotoxicosis and cytopenias.

Hypothesis and objectives: To characterize the observed incidence, timing, and risk factors for AZA hepatotoxicosis in dogs treated clinically, and to determine the relationship between the development of hepatotoxicosis and cytopenias.

Animals: Fifty-two dogs treated with AZA with clinical and biochemical follow-up, with a subset of 34 dogs available for determination of changes in liver enzyme activities in serum.

Methods: Retrospective medical record review, from January 2009 through December 2013.

Results: Hepatotoxicosis (as defined by a >2-fold increase in serum ALT) was observed in 5 of 34 dogs (15%) within a median onset of 14 days (range, 13-22 days). Dogs had a median 9-fold increase in ALT and 8-fold increase in ALP, which stabilized or resolved with drug discontinuation or dose reduction. German shepherds were significantly over-represented (3 of 5 dogs with hepatotoxicosis; P = .0017). Thrombocytopenia or neutropenia were seen in 4 of 48 dogs with CBC follow-up (8% of dogs), but occurred significantly later in treatment (median onset, 53 days; range 45-196 days) compared to hepatotoxicosis (P = .016).

Conclusions and clinical importance: These results support the routine monitoring of liver enzymes during the first 1-4 weeks of AZA treatment in dogs, with continued monitoring of the CBC. Additional studies are warranted to characterize the apparently higher risk of AZA hepatotoxicosis in German shepherds.

Keywords: ALT; German shepherd; Liver toxicosis; Thiopurines.