Acute Liver Failure due to Enalapril

Abstract

This report presents a 46-year-old man who was treated for hypertension with the angiotensin-converting-enzyme (ACE) inhibitor enalapril. After 3 years of continuous treatment he presented with jaundice and progressive liver failure that continued despite withdrawal of the medication. The patient was taking no other medication. All known causes of acute liver failure could be excluded indicating a drug-induced liver damage after long-term treatment with enalapril. Analysis of liver biopsies revealed a pathomorphological pattern comparable to than observed in severe halothane hepatitis. Serological studies including T-cell stimulation with enalapril and a broad spectrum of tests for autoimmunity including autoantibodies against calreticulin, the major Ca2+ and Zn2+ binding protein of the endoplasmic reticulum and suggested to be involved in the pathogenesis of halothane hepatitis were negative. Thus, the mechanism of enalapril-induced liver injury remains obscure. Liver failure progressed and finally led to orthotopic liver transplantation. To our knowledge, this is the longest duration of chronic treatment with an ACE inhibitor before liver failure occurred. In addition, liver failure progressed despite withdrawal of the medication. It is concluded that even after long-term treatment with an ACE inhibitor liver failure may be induced. Therefore, regular monitoring of liver enzymes should be considered.

Phenprocoumon-induced liver disease ranges from mild acute hepatitis to (sub-) acute liver failure

“…Thus, an involvement of Enalaprilat in the liver damage of case 3 can not be completely excluded, although Enalaprilat-induced liver disease depicts rather a cholestatic than a hepatitic picture as reported in case 3 and most phenprocoumon-induced liver diseases [42]. Noteworthy, Enalaprilat-induced liver failure has only been described twice [43,44]. Phenacetin (case 2) taken low dose on demand is not likely to induce a fulminant hepatitis with consecutive liver failure.…”

“…A direct damage of hepatocytes by reactive metabolites of oral anticoagulants resulting in an augmented antigenicity and consecutive immuno -allergic reaction is considered to be responsible for anticoagulant induced liver damage [44]. Eosinophilic granulocytes as seen in all of our patients liver specimens and the slow resolution of the hepatocyte damage suggest that drug-related antigens persist in the liver for weeks triggering an allergic reactions [47,48].…”

“…1c and d; cases 1 and 5). An increase of eosinophilic granulocytes was recognised in most samples, a histological feature which is often described in the context of drug-induced hepatitis [44].…”

Toxicidad hepática causada por medicamentos: revisión estucturada

“…medicamentos se asoció con la mejoría de los pacientes, aunque existen reportes de muerte con amiodarona (47). Los antihipertensivos como enalapril elevaron las cifras de enzimas hepáticas y produjeron ictericia y cambios estructurales en el hígado confirmados por biopsia, que llevaron al trasplante y muerte (48). Para metildopa (probable) se identificaron 9 reportes de casos de toxicidad hepática de (62), ciprofloxacina y trovafloxacina (retirada del mercado).…”

Ductopenic hepatitis related to Enalapril

“…Although in our case, the adverse effect happened 2 years after starting Enalapril, the hepatotoxicity of this drug is very well-known and the latent period to develop liver injury is very variable [1,6]. In some cases, symptoms improve immediately after discontinuation of the drug.…”