Hepatotoxicity Associated with Low-dose, Long-term Methotrexate Treatment of Rheumatoid Arthritis

Liver biopsies were performed in 17 patients with therapy-refractory rheumatoid arthritis who were treated successfully with 5–15 mg/week methotrexate (mtx). The average duration of exposure to mtx therapy for each patient was 2.8 years (range 1.5–5 years). Total cumulative mtx doses ranged between 633 and 1655 mg (mean 1060 mg). The biopsies revealed 16 cases of normal histology, of which 3 showed nuclear variability in the hepatocytes; 4 with mild fatty infiltration, 2 with mild fatty infiltration and portal round cell infiltration. Portal fibrosis was found in one patient who had psoriasis in addition to clinical RA.