A case of anastrazole-related drug-induced autoimmune hepatitis

An otherwise asymptomatic 66-year-old British Caucasian female with a history of breast cancer was referred by the oncologists due to progressively abnormal liver function tests (LFTs). After undergoing wide local excision and axillary dissection she was started on the anti-oestrogen drug Arimidex (anastrozole) as the tumour cells were oestrogen receptor positive. With a background of normal LFTs, an absence of risk factors for chronic liver disease and otherwise good health, 6 months after starting Arimidex the oncology team noted deranged LFTs. Her hepatitis screening including hepatitis A-C, HSV, HIV, CMV and EBV serology and metabolic screening was negative. Liver ultrasound was essentially normal.The autoimmune screening was positive for ANA (1:160) and weakly positive for anti-smooth muscle antibody (1:80). A liver biopsy demonstrated heavy portal tract inflammation, associated interface hepatitis, and numerous necroinflammatory foci throughout the liver parenchyma. There was also a moderate to marked mixed inflammatory infiltrate of mainly plasma cells and lymphocytes with scattered eosinophils and neutrophils, which best reflects drug-induced liver injury (DILI), although potentially could also correspond with autoimmune hepatitis.The exact mechanism of liver injury from anastrazole is not very clear, but metabolic and immune-mediated damage and individual susceptibility are likely involved in what are often idiosyncratic reactions. The type of cellular immune recruitment (e.g., T-helper cells) reflects the chronicity of injury, with the potential to prolonged liver derangement months or years beyond the period of drug exposure such that DILI may mimic and/or cause drug-induced autoimmune hepatitis.