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 1,655 mg (mean 1,060 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.