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Clinical, clinicopathologic, and hepatic histopathologic features associated with probable ketoconazole-induced liver injury in dogs: 15 cases (2015–2018)

Luis P. Macho1Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.

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Sharon A. Center1Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.

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John F. Randolph1Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.

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Lee Ann Dumars3Pet Medical Center and Spa, Fresno, CA 93711.

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Susan E. Rush4Animal Clinic of La Plata, La Plata, MD 20646.

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Mary Kate Cameron5Cameron Veterinary Hospital, Sunnyvale, CA 94087.

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John M. Lucy6Oradell Animal Hospital, Paramus, NJ 07652.

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Deborah L. Hall-Fonte6Oradell Animal Hospital, Paramus, NJ 07652.

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Sean P. McDonough2Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.

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Jeanine Peters-Kennedy2Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.

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Jacqueline Marinoff2Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.

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Jennifer Harrison7Dogs and Cats Veterinary Referral, Bowie, MD 20715.

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Bethany Sabatino8Affiliated Veterinary Specialists, Gainesville, FL 32607.

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Krysta Deitz9Southeastern Veterinary Oncology and Internal Medicine, Jacksonville, FL 32250.

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Abstract

OBJECTIVE

To characterize clinical, clinicopathologic, and hepatic histopathologic features and outcome for dogs with probable ketoconazole-induced liver injury.

ANIMALS

15 dogs with suspected ketoconazole-induced liver injury that underwent liver biopsy.

PROCEDURES

Medical record data were summarized regarding signalment, clinical signs, clinicopathologic and hepatic histopathologic findings, concurrent medications, ketoconazole dose, treatment duration, and outcome.

RESULTS

Median age and body weight were 8.2 years (range, 5 to 15 years) and 13.0 kg (28.6 lb; range, 8.2 to 38.0 kg [18.0 to 83.6 lb]), respectively. The most common breed was Cocker Spaniel (n = 5). All dogs received ketoconazole to treat cutaneous Malassezia infections. Median daily ketoconazole dose was 7.8 mg/kg (3.5 mg/lb; range, 4.4 to 26.0 mg/kg [2.0 to 11.8 mg/lb]), PO. Treatment duration ranged from 0.3 to 100 cumulative weeks (intermittent cyclic administration in some dogs); 6 dogs were treated for ≤ 10 days. Common clinical signs included lethargy, anorexia, and vomiting. All dogs developed high serum liver enzyme activities. Hepatic histopathologic findings included variable lobular injury, mixed inflammatory infiltrates, and conspicuous aggregates of ceroid-lipofuscin–engorged macrophages that marked regions of parenchymal damage. Five dogs developed chronic hepatitis, including 3 with pyogranulomatous inflammation. Of the 10 dogs reported to have died at last follow-up, survival time after illness onset ranged from 0.5 to 165 weeks, with 7 dogs dying of liver-related causes.

CONCLUSIONS AND CLINICAL RELEVANCE

Findings for dogs with hepatotoxicosis circumstantially associated with ketoconazole treatment suggested proactive monitoring of serum liver enzyme activities is advisable before and sequentially after initiation of such treatment.

Abstract

OBJECTIVE

To characterize clinical, clinicopathologic, and hepatic histopathologic features and outcome for dogs with probable ketoconazole-induced liver injury.

ANIMALS

15 dogs with suspected ketoconazole-induced liver injury that underwent liver biopsy.

PROCEDURES

Medical record data were summarized regarding signalment, clinical signs, clinicopathologic and hepatic histopathologic findings, concurrent medications, ketoconazole dose, treatment duration, and outcome.

RESULTS

Median age and body weight were 8.2 years (range, 5 to 15 years) and 13.0 kg (28.6 lb; range, 8.2 to 38.0 kg [18.0 to 83.6 lb]), respectively. The most common breed was Cocker Spaniel (n = 5). All dogs received ketoconazole to treat cutaneous Malassezia infections. Median daily ketoconazole dose was 7.8 mg/kg (3.5 mg/lb; range, 4.4 to 26.0 mg/kg [2.0 to 11.8 mg/lb]), PO. Treatment duration ranged from 0.3 to 100 cumulative weeks (intermittent cyclic administration in some dogs); 6 dogs were treated for ≤ 10 days. Common clinical signs included lethargy, anorexia, and vomiting. All dogs developed high serum liver enzyme activities. Hepatic histopathologic findings included variable lobular injury, mixed inflammatory infiltrates, and conspicuous aggregates of ceroid-lipofuscin–engorged macrophages that marked regions of parenchymal damage. Five dogs developed chronic hepatitis, including 3 with pyogranulomatous inflammation. Of the 10 dogs reported to have died at last follow-up, survival time after illness onset ranged from 0.5 to 165 weeks, with 7 dogs dying of liver-related causes.

CONCLUSIONS AND CLINICAL RELEVANCE

Findings for dogs with hepatotoxicosis circumstantially associated with ketoconazole treatment suggested proactive monitoring of serum liver enzyme activities is advisable before and sequentially after initiation of such treatment.

Contributor Notes

Address correspondence to Dr. Center (sac6@cornell.edu).