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Anti-Arrhythmic Induced Jaundice: A Case Report
Michaud, C. D.O.; Fishman, A. D.O.; Spinale, J. D.O.
Kent Hospital, Internal Medicine Residency Program; Warwick, RI
Introduction: Amiodarone is a highly lipophilic, iodinated benzofuran derivative and a
class III antiarrhythmic agent. Used routinely for management of atrial fibrillation,
amiodarone inhibits adrenergic stimulation by its action in blocking membrane ion
channels, decreasing AV nodal conduction through disruption of the lipid membrane
bilayer. It is concentrated in many tissues and cells including hepatocytes in the liver
where it is metabolized extensively. Amiodarone is a common cause of elevated
aminotransferases, but an uncommon cause of drug induced liver injury (DILI). We
present a case of amiodarone-induced cholestatic hepatitis with a rare pattern of injury
for this medication, which most often causes a steatohepatitis.
Case: An 80-year-old white male with history of atrial fibrillation and systolic heart failure
presented with three days of yellowing skin, pruritus and dark urine Five months prior to
his presentation, he was hospitalized for treatment of a retroperitoneal abscess in which
he received a six-week course of rifampin and nafcillin. The only other new medications
included amiodarone, which was started eight months prior. On exam, he was in no
acute distress with normal vital signs. Pertinent findings included jaundice and scleral
icterus. He had no hepatosplenomegaly, abdominal distension, tenderness, asterixis, or
signs of chronic liver disease. His initial laboratory studies demonstrated a pattern
consistent with cholestasis: alkaline phosphatase 1166 U/L, AST 273 U/L, ALT 209 U/L,
total bilirubin 16.6 U/L, and direct bilirubin 9.46 U/L. Upon review of his history, it was
noted that his liver enzymes had begun to increase prior to the addition of antibiotics five
months prior. Amiodarone was discontinued upon admission however his enzymes
continued to rise over the next two days. Hospital work-up revealed a sedimentation
rate >120 and a positive CMV IgM antibody. Given the continued rise in liver enzymes,
a liver biopsy was obtained revealing cholestatic hepatitis consistent with drug-induced
hepatic injury; there was no evidence of viral hepatitis or cardiac cirrhosis. Over the
course of his admission, the patient’s liver enzymes improved, as did his clinical
cholestatic picture. By discharge, laboratory abnormalities and clinical exam had
returned to normal.
Discussion: Up to fifty percent of acute jaundice presentations are caused by drugs,
however the specific offending agents are not always as common. Acetaminophen and
antibiotics, especially amoxiciliin-clavulanate, are the two most common culprits of DILI
with injury patterns ranging from cholestatic to hepatocellular, or mixed patterns. While
DILI is a common problem, amiodarone is not a common drug to be implicated.
Clinically significant liver disease occurs in 1% of patients on amiodarone therapy,
however with the growing number of elderly patients on amiodarone for atrial fibrillation,
there is even more reason for diligent monitoring and attunement. The most feared
complication of DILI is fulminant hepatic failure or slow progression to cirrhosis that has
variable resolution with removal of the offending agent. It is imperative to recognize the
potential for hepatic toxicity caused by amiodarone as well as the fact that the pattern for
enzyme elevations and histologic appearance of liver biopsy can vary in amiodaroneinduced
liver injury such that the typical transaminitis and hepatocellular steatohepatitis
will not always be seen.