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When a patient taking methotrexate should have a liver biopsy to assess for liver damage is a difficult and critical question for rheumatologists. It is not cost effective nor medically necessary to perform biopsies on all patients after a specific dose of methotrexate has been reached, nor after they have been treated for a definite length of time. Clinicians should take into account a patient's possible pre-existing factors (hepatitis, diabetes, obesity, past and present alcohol consumption), concomitant medications, intercurrent illnesses and serial laboratory evaluations when assessing the need for a biopsy in an individual patient being treated with methotrexate.