Hepatotoxicity associated with angiotensin-converting enzyme inhibitors.
OBJECTIVE
To review published reports of hepatotoxicity associated with angiotensin-converting enzyme (ACE) inhibitors and to explore possible mechanisms of injury.


METHODS
Published reports of hepatotoxicity associated with use of ACE inhibitors and investigations that suggest potential mechanisms of injury.


RESULTS
Nineteen 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.


CONCLUSIONS
Hepatotoxicity, 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 eicosanoid metabolism provides a plausible explanation for cross-reactivity among ACE inhibitors. Hepatotoxicity resolves if ACE inhibitors are stopped but may progress to liver failure if treatment is continued.
Hagley
M T
MT
Akron City Hospital, OH.
Hulisz
D T
DT
Burns
C M
CM
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D002216:Captopril / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury; D004656:Enalapril / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D002216:Captopril