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Hepatotoxicity related to itraconazole: report of three cases
B Adriaenssens1, T Roskams, P Steger
1Departement Inwendige Ziekten, dienst Lever-, Galblaas- en Pancreasziekten, Universitair ZiekenhuisGasthuisberg Katholieke Universiteit Leuven 3000 Leuven, België.
Background:
The antimycotic synthetic azole compounds are known to lead to toxic liver injury. The occurrence of acute hepatitis is best known for ketoconazole. With itraconazole, hepatotoxic reactions have only very rarely been reported, and histologic data are lacking. We report on three patients who developed acute liver damage during therapy with itraconazole, and in whom liver biopsy specimens were obtained.
Methods:
Three patients with apparent itraconazole-induced liver injury were studied. Clinical, laboratory, serologic, and histologic data of all three cases were analyzed.
Results:
All three patients developed a biochemical-histologic pattern of cholestatic liver injury with damage to the interlobular bile ducts. Beginning ductopenia was present in two, suggesting that itraconazole might be responsible for the occurrence of prolonged drug-induced cholangiopathy. Jaundice was the presenting symptom in all three. It was not accompanied by clinical hallmarks of hypersensitivity, which is suggestive for metabolic rather than for immunoallergic idiosyncrasy.
Conclusions:
Itraconazole-induced liver injury presents with a cholestatic pattern of injury with damage to the interlobular bile ducts, possibly leading to ductopenia. We suggest that itraconazole should be added to the list of drugs that may be responsible for a drug-induced vanishing bile duct syndrome. Further histologic documentation in other cases is necessary to strengthen our current findings.
Insights
Itraconazole can cause liver injury, presenting as cholestatic hepatitis with bile duct damage. This suggests itraconazole may contribute to vanishing bile duct syndrome, requiring further study.
Area of Science:
- Hepatology
- Pharmacology
- Toxicology
Background:
- Synthetic azole antifungals are associated with drug-induced liver injury.
- Ketoconazole is a known cause of acute hepatitis.
- Hepatotoxicity from itraconazole is rare, with limited histologic data.
Observation:
- Three patients developed liver damage during itraconazole therapy.
- Liver biopsies revealed a cholestatic pattern with interlobular bile duct injury.
- Jaundice was the primary symptom, without hypersensitivity signs.
Findings:
- Itraconazole-induced liver injury exhibits a cholestatic pattern and bile duct damage.
- Two patients showed early ductopenia, indicating potential drug-induced cholangiopathy.
- The injury pattern suggests a metabolic rather than immunoallergic mechanism.
Implications:
- Itraconazole may cause drug-induced vanishing bile duct syndrome.
- This study highlights the need for increased awareness of itraconazole hepatotoxicity.
- Further research with histologic evidence is needed to confirm these findings.