In this report, we present the clinical features of two patients with amiodarone-induced reversible and irreversible hepatotoxicity, highlighting the importance of close monitoring of liver enzymes and evaluation of liver CT imaging as well as liver biopsy during treatment with amiodarone. Approximately 25% of patients using amiodarone develop a transient asymptomatic increase in serum aminotransferase levels that resolves spontaneously or after dose reduction [
4]. Amiodarone-induced symptomatic hepatitis, cirrhosis, and fatal hepatic failure are extremely rare (0–3%) [
4,
5]. However, when the diagnosis is established, the mortality risk may be as high as 60% at 5 months [
6]. Histological features of amiodarone-induced hepatotoxicity are similar to alcoholic hepatitis and characterized by Mallory bodies, leukocyte infiltration, steatosis, and ballooning of hepatocytes [
7]. Amiodarone and its metabolites accumulate in lysosomes of hepatocytes and lead to inhibition of phospholipase A1 and A2, which inhibits removal of lysosomal lipids and leads to phospholipidosis [
8]. As with our patients, this mechanism leads to steatohepatitis and finally to irreversible liver cirrhosis. The presence of lamellar lysosomal inclusion bodies visualized by electron microscopy is a typical pathological finding of amiodarone-induced hepatotoxicity [
7]. In patient 1, amiodarone was continued under the conditions of elevated liver enzymes in addition to the use of corticosteroids that could cause liver injury or accelerate his underlying liver injury, and it led to irreversible fatal hepatic failure. However, in patient 2, amiodarone was discontinued immediately after the detection of liver enzyme elevation and led to improvement of liver function. According to these two clinical courses, amiodarone should be discontinued immediately if amiodarone-induced liver injury is suspected.
Amiodarone is a lipophilic agent and tends to accumulate in lipid-laden organelles such as the liver. It is reported that a concentration of amiodarone and its metabolite,
N-desethylamiodarone, in the liver may be as high as 500-fold of the serum level [
9].
Previous reports showed that the plasma amiodarone level may be poorly correlated with its toxicity [
10]. However, high liver density seen on CT scans, which is secondary to increased iodine content of amiodarone and reflects the tissue level of amiodarone, may be useful to detect the toxicity [
11]. In this regard, it is important to evaluate elevations of liver enzymes, liver CT imaging (high attenuation of the liver parenchyma), and histology, and discontinuation should be considered when amiodarone-induced hepatotoxicity is suspected. Alternative strategies, such as catheter ablation and/or an implantable cardioverter defibrillator implant could be considered for such patients.