Acarbose-Potentiated Acetaminophen-Induced Liver Failure: A Dually Mediated Hepatotoxicity

Abstract

Purpose: A 43-year-old woman, with diabetes placed on acarbose. On follow-up over two years, her liver enzymes were normal. Two years later, she presented with jaundice, with markedly elevated liver enzymes, and prolonged prothrombin time. She was taking Excedrin (acetaminophen, aspirin, caffeine), for headache at an average dose of 1 gm four times daily for two weeks prior to her presentation. As medicines were discontinued, she underwent work-up, which revealed a positive anti-smooth muscle antibody (SMA). The rest of work-up was negative or normal. Liver enzymes peaked immediately as acarbose and Excedrin were discontinued, and liver biopsy revealed extensive necrosis. A few days later, all enzymes and bilirubin took a downward trend to normalization over 6 weeks (Figure 1). Discussion: Acarbose is an inhibitor of intestinal glucosidases used in type II diabetes, with rare liver injury. Acetaminophen is a common cause of drug-induced liver failure, with non-toxic doses blamed for liver failure as in chronic alcoholic use, or co-administration with other drugs that share the same metabolic pathway as acetaminophen. Animal studies suggested that acarbose especially at high doses can potentiate acetaminophen hepatotoxicity by inducing hepatic CY2E1. SMA supported by liver pathology suggests an immune-mediated basis of liver injury in this case, precipitated by acarbose-acetaminophen co-administration involving a unique dual mechanism. This is the first case of acarbose-induced hepatotoxicity that also carried features of autoimmune hepatitis.Figure: [443]Conclusion: We presented for the first time a case of acarbose-potentiated acetaminophen induced liver injury masquerading as autoimmune hepatitis. Co-administration of Tylenol and acarbose should be closely monitored for hepatotoxicity.