LAUSR

A 5-year-old spayed female Portuguese water dog was presented to a veterinary teaching hospital on referral for marked liver enzyme elevation (aspartate transaminase [AST] 1473 IU/L [ref: 15–66 IU/L], alanine transaminase [ALT] 1152 IU/L [ref: 12–118 IU/L], alkaline phosphatase [ALP] 1907 IU/L [ref: 5–131 IU/L]), hyperbilirubinemia (total bilirubin 35.9 μmol/L [ref: 1.71–5.13 μmol/L]), a leukocytosis characterized by a mature neutrophilia of 15.7 x 109 cells/L (ref: 2.1–10.6 x 109 cells/L), coughing and gagging. Hematocrit was 0.53 L/L (ref: 0.36–0.60 L/L) and total protein was 64 g/L (ref: 50–74 g/L). Four days prior to presentation, the dog began vomiting and became lethargic and hyporexic with the development of a hacking cough. Physical examination showed bilaterally enlarged mandibular lymph nodes and salivary glands, pain on opening of the mouth, reduced right cranial bronchovesicular sound on auscultation, and a cough on tracheal palpation. Cytology of the salivary glands and lymph nodes showed a neutrophilic to lymphohistiocytic sialadenitis and reactive lymphoid hyperplasia with neutrophilic infiltration. Thoracic radiographs revealed a diffuse bronchointerstitial pattern, and the cough, gag, and auscultatory findings were attributed to presumed aspiration pneumonia. Pertinent history included being fed a raw diet and living with four other dogs in a rural/ agricultural setting. An initial abdominal ultrasound was consistent with pancreatitis and possible hepatitis (patchy hyperechoic pancreatic regions and peripancreatic adipose tissue, and mild hypoechoic liver) with a normal gallbladder appearance. The dog was treated with ampicillin, enrofloxacin, methadone, metronidazole, N-acetylcysteine, and gastrointestinal supportive medications. The liver enzymology and hyperbilirubinemia worsened, so serial ultrasounds were performed which revealed progressive gallbladder wall thickening with no evidence of bile duct obstruction, and resolution of pancreatic changes. Antibiotics were switched to clindamycin and ceftazidime, and ursodiol, vitamin E, and an anti-inflammatory dose of dexamethasone SP were added to the treatments. Four wedge laparoscopic liver biopsy samples were obtained and revealed moderate to marked midzonal to centrilobular hepatocellular swelling and clearing (consistent with a steroid hepatopathy), canalicular bile stasis, and neutrophilic and lymphoplasmacytic portal infiltrates (Fig. 1). Copper quantification was normal (125 ppm), and additional diagnostics for infectious agents—including a liver culture, fecal float and sediment examination, Toxoplasma titers, and vector-borne disease panel (Anaplasma, Babesia, Bartonella, Ehrlichia, hemotrophic Mycoplasma, Rickettsia, Borrelia burgdorferi, Dirofilaria immitus)—were negative. At the time of presentation, the patient was negative for IgM antibodies to Leptospira canicola, L. grippotyphosa, L. icterohaemorrhagiae, and L. pomona (WITNESS canine leptospira antibody test). Six days following presentation, Leptospira polymerase chain reaction and titers (L. pomona, L. icterohaemorrhagiae, L. canicola, L. grippotyphosa, L. hardjo, L. autumnalis, and L. bratislava) were negative, and convalescent titers 7 days later were 1:50 for L. icterohaemorrhagiae. The patient continued to decline with progression of aspiration pneumonia, progressive acute kidney injury, worsening icterus, and an esophagostomy tube site infection with multiple drug-resistant Enterobacter cloacae complex and methicillinresistant Staphylococcus pseudintermedius. Over the course of treatment, the sialadenitis resolved, but liver enzymes (ALT 344 IU/L [ref: 16–91 IU/L], AST 94 IU/L [ref: 23–65 IU/L], ALP 1693 IU/L [ref: 20–155 IU/L], γ-glutamyl transferase [GGT] 152 IU/L [ref: 7–24 IU/L]) remained elevated with ALP and GGT greater than 4× the upper reference interval at the time of discharge, 19 days following presentation. Hyperbilirubinemia continued to increase, reaching 513 μmol/L (ref: 1.71–5.13 μmol/L) at the time of euthanasia, 29 days following presentation. An autopsy was performed 2 days later (31 days following presentation), and significant macroscopic changes included marked generalized icterus, mild hepatomegaly with an enhanced reticular pattern and yellow-green discoloration, and a shrunken gallbladder surrounded by increased fibrous connective tissue and devoid of bile (Fig. 2). 1098432 VETXXX10.1177/03009858221098432Veterinary Pathology XX(X)Harvey et al research-article2022