Therapy with the anti-arrhythmic agent amiodarone may be associated with liver disease.
Mechanism: drug-induced phospholipidosis (see Chapter 32). The intravenous formulation of amiodarone contained polysorbate 80 as a solubilizer, which is associated with centrizonal necrosis.
Clinical features:
(1) hepatomegaly
(2) elevation in serum liver function tests
(3) symptoms of phospholipidosis affecting other organs (lung, etc)
Histologic findings in a liver biopsy:
(1) phospholipidosis with numerous Mallory bodies, mimicking alcoholic hepatitis
(2) variable steatosis
(3) variable cholangitis
(4) fibrosis which may progress to cirrhosis
Mild to moderate changes revert on discontinuation of amiodarone therapy.
Risk factors for significant liver damage:
(1) continued therapy with amiodarone (although hepatoxicity may appear after only a few doses) after development of hepatotoxicity
(2) intravenous infusion
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