A 48-year-old woman with autoimmune hepatitis (AIH) type 1 (ANA+, anti-SMA+) is on azathioprine 1.5 mg/kg/day and prednisolone 5 mg/day with normal ALT in remission. She now needs long-term management. Which parameter is MOST important to check before dose adjustment of azathioprine?
- A TPMT (thiopurine S-methyltransferase) enzyme activity or genotype ✓
- B Serum IgG level
- C Anti-dsDNA antibody titre
- D Liver biopsy Ishak score at 2 years
Explanation
Azathioprine is metabolised by thiopurine S-methyltransferase (TPMT). Patients with low or absent TPMT activity (6-11% heterozygous, 0.3% homozygous deficient) are at risk of severe thiopurine toxicity (myelosuppression, hepatotoxicity) when given standard doses. TPMT phenotyping or genotyping before initiating or significantly escalating azathioprine dose is recommended to identify at-risk patients. IgG normalisation is a marker of biochemical response in AIH but not for drug dosing. Anti-dsDNA is relevant for lupus overlap. Liver biopsy at 2 years helps assess histological remission but does not guide azathioprine dosing.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.