2280 Propafenone-Induced Hepatocellular and Cholestatic Injury

Abstract

INTRODUCTION: Propafenone, an antiarrhythmic medication, decreases cardiac automaticity and increases refractory periods slowing cardiac conduction. Propafenone-induced hepatic injury is rare with only eight reported cases in the literature. We report a case of propafenone-induced hepatic injury in a patient presenting with painless jaundice. CASE DESCRIPTION/METHODS: A 60-year-old woman presented with sudden onset jaundice and a one week history of 10-pound weight loss, right upper quadrant abdominal pain, nausea and vomiting. Two months prior to presentation, she was diagnosed with atrial fibrillation and was begun on Propafenone 325 mg oral twice daily. She had no history of alcohol, drugs, or herbal medication use. Physical exam was significant only for generalized jaundice. On admission, laboratory studies were significant for AST 304 IU/L, ALT 601 IU/L, ALP 334 IU/L, total bilirubin 7.9 mg/dL, and direct bilirubin 5.4 mg/dL.Abdominal ultrasound revealed fatty liver without biliary obstruction. CT abdomen was unremarkable for hepatic or biliary pathology. Viral serologic markers and acetaminophen levels were negative as well as workup for Autoimmune hepatitis, and Primary biliary cholangitis. Liver biopsy revealed steatohepatitis with superimposed ductular and centrilobular cholestasis suggestive of drug-induced injury.The patient was begun on N-Acetylcysteine and Propafenone was discontinued. Several days after withdrawal of Propafenone, liver function tests began to improve slowly. The patient was discharged home and one month later, transaminases returned to normal and jaundice had resolved. DISCUSSION: Propafenone is a Class 1C antiarrhythmic indicated for symptomatic atrial fibrillation without structural abnormalities. The mechanism for hepatic injury is unknown. Like in our patient, the injury is self-limited and has not been linked to acute liver failure, chronic liver injury, or vanishing bile duct syndrome. Once identified as the cause, the medication should be immediately stopped and never prescribed because re-exposure is associated with recurrence of symptoms. As in other reports, our patient’s liver injury occurred within a 2-6-week period after exposure and, resolved 3-5 weeks after cessation of the offending medication. Propafenone-induced hepatic injury should be suspected in a patient presenting with hepatocellular and cholestatic injury, especially in a patient recently begun on that medication after exclusion of other causes of abnormal liver function.