Histopathologic findings in the liver of rheumatoid arthritis patients treated with long-term bolus methotrexate

Twenty-three patients with severe rheumatoid arthritis were treated with oral methotrexate (MTX) for more than 10 years. MTX was given as a bolus of 5-15 mg/week; the total cumulative dose ranged from 4,690 mg to 10,230 mg. Liver biopsies were performed on 21 of the patients to assess possible fibrosis and cirrhosis. Grade I histopathologic changes were found in 13 of the 21 biopsy samples, grade II changes were found in 3, and grade IIIA changes (mild fibrosis) were found in 5 specimens. None of the biopsy samples showed cirrhosis. Repeat biopsies were performed on the 5 patients with grade IIIA changes while they were still taking MTX. No progression of the fibrosis was noted. Two of the 5 samples, however, were graded IIIB because of portal and perilobular inflammation. Our findings support the premise that prolonged administration of oral MTX, when given as a weekly bolus at a low dose, does not cause cirrhosis or severe fibrosis in the rheumatoid arthritis patient who does not abuse alcohol.