Hepatotoxicity Associated with Angiotensin-Converting Enzyme Inhibitors

ObjectiveTo review published reports of hepatotoxicity associated with angiotensin-converting enzyme (ACE) inhibitors and to explore possible mechanisms of injury.Data SourcesPublished reports of hepatotoxicity associated with use of ACE inhibitors and investigations that suggest potential mechanisms of injury.Data SynthesisNineteen cases of ACE-inhibitor–associated hepatotoxicity are presented. Early theories regarding mechanisms are reviewed. Laboratory investigations of hepatic effects of eicosanoids on hepatic function are reviewed and a novel mechanism by which ACE inhibitors may cause hepatic injury is postulated.ConclusionsHepatotoxicity, usually cholestatic in nature, has been reported with captopril, enalapril, and lisinopril use. Apparent cross-reactivity has been reported twice. Potential mechanisms of injury include idiopathic hypersensitivity and modulation of eicosanoid metabolism by inhibition of kininase II and subsequent increased hepatic bradykinin activity. Mediation via altered eicosan...