A fatal case of bupropion (Zyban) hepatotoxicity with autoimmune features: Case report

Abstract

Background: Bupropion is approved for the treatment of mood disorders and as an adjuvant medication for smoking cessation. Bupropion is generally well tolerated and considered safe. Two randomized controlled trials of bupropion therapy for smoking cessation did not report any hepatic adverse events. However, there are three reports of severe but non-fatal bupropion hepatotoxicity published in the literature.

Case presentation: We present the case of a 55-year old man who presented with jaundice and severe hepatic injury approximately 6 months after starting bupropion for smoking cessation. Laboratory evaluation demonstrated a mixed picture of hepatocellular injury and cholestasis. Liver biopsy demonstrated findings consistent with severe hepatotoxic injury due to drug induced liver injury. Laboratory testing was also notable for positive autoimmune markers. The patient initially had clinical improvement with steroid therapy but eventually died of infectious complications.

Conclusion: This report represents the first fatal report of bupropion related hepatotoxicity and the second case of bupropion related liver injury demonstrating autoimmune features. The common use of this medication for multiple indications makes it important for physicians to consider this medication as an etiologic agent in patients with otherwise unexplained hepatocellular jaundice.

Figure 1

Serial serum alanine aminotransferase and total bilirubin levels. The patient's serum ALT and total bilirubin initially improved with a short course of oral corticosteroids. However, 3 weeks after discontinuing the prednisone, his serum ALT markedly increased and he was rehospitalized. Despite high doses of corticosteroids, he developed progressive mental status changes and died 105 days after initial presentation with sepsis and liver failure.

Figure 2

Liver biopsy. (Top) H&E stain showing severe necrosis in the peri-portal region with a mixed population of lymphocytes, eosinophils, and small clusters of plasma cells. (Bottom) Reticulin stain showing crowded reticulin meshwork and drop out of hepatocytes consistent with hepatic collapse. (Magnification of top and bottom, ×400 and ×200).