What are the most common differentials for elevated ALT and ALP in dogs and how do I prioritize workup?

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The most common differentials for elevated alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in dogs span primary hepatic disease and reactive hepatopathy (RH) secondary to extrahepatic disease. Distinguishing between these two categories drives the workup priority. Primary hepatic (PH) disease and RH both produce ALT and ALP elevation, but the magnitude of ALT rise helps differentiate them. ALT is significantly higher in dogs with PH compared to dogs with RH, because hepatocellular damage in RH is usually limited. Although overlap exists between the two groups, the degree of ALT elevation aids in distinguishing PH from RH. 3 Infectious disease — specifically ehrlichiosis — is a pertinent extrahepatic cause to include on the differential list. Mild increases in ALT and ALP are the most common serum biochemical abnormalities in dogs infected with Ehrlichia ewingii, and similar hepatic enzyme elevations are reported with E. canis and Anaplasma phagocytophilum. Concurrent abnormal or reactive lymphocytes, neutrophilia, or thrombocytopenia should raise suspicion for canine granulocytic ehrlichiosis as the underlying driver. 4 Adrenal disease belongs on the differential when ALP elevation is prominent. ALP is elevated in 75.9% of dogs undergoing adrenalectomy, and ALT is elevated in 41.4% of the same population, reflecting the high frequency of hepatic enzyme abnormalities associated with adrenal pathology in dogs. 6 ALP has the lowest diagnostic specificity of routinely used liver enzymes in dogs, owing to induction of multiple isozymes; elevated ALP is the most common biochemical abnormality on routine testing for hepatic disease and cannot be interpreted as primary hepatic disease without further workup, including liver biopsy in many cases. 2 Workup prioritization should follow the 3 P's framework: Prognostic, Practical, and Pertinent. Tests should be selected based on whether findings will change prognosis or treatment, whether the budget allocation favo