CYP2D6 polymorphism may contribute to Trazodone-induced hepatotoxicity: a rare case of drug-drug-gene induced liver injury

A 46-year-old female with a history of type I diabetes, alopecia areata and autoimmune hypothyroidism presented with a significant hepatocellular hepatitis. The top 3 differential diagnoses were drug-induced liver injury, autoimmune hepatitis and drug-induced autoimmune hepatitis. Considering the predisposition for immune-mediated conditions, we performed a liver biopsy to exclude an autoimmune hepatitis. A temporal relationship between the onset of liver injury and the start of Trazodone and Escitalopram was observed. We report a case of Trazodone-induced liver injury in which pharmacogenomic testing identified a CYP2D6 gene polymorphism leading to CYP2D6 dysfunction and accumulation of Trazodone’s potential hepatotoxic metabolite m-CPP, which elucidates the underlying pathogenesis. This case also presents an example of a drug-drug-gene interaction between Trazodone and the not-so-innocent bystander Escitalopram leading to an additional component of CYP2D6 inhibition. This case highlights the potential benefit of targeted pharma-cogenomic testing to minimise the risk of drug-induced liver injury.

Keywords: drug-induced liver injury, acute hepatocellular hepatitis, Trazodone-induced hepatotoxicity, CYP2D6 dysfunction, drug-drug-gene interaction, pharmacogenomics.