Hepatic ultrastructure after methotrexate therapy for rheumatoid arthritis

Twenty‐six patients receiving long‐term oral methotrexate (MTX) therapy for rheumatoid arthritis (24 patients) or psoriasis (2 patients) were prospectively evaluated for alterations in liver morphology by light microscopy, electron microscopy, and immunofluorescence microscopy. Although only 4 MTX‐treated patients had light microscopic evidence of mild fibrosis, all had evidence of collagen deposition in the space of Disse near Ito cells and changes in hepatocyte lysosomes on electron microscopy. These findings were absent from control livers. Fibrinogen, fibronectin, and type IV collagen were identified by immunofluorescence in both MTX‐treated patients and controls. We conclude that long‐term MTX therapy for rheumatoid arthritis is associated with alterations in hepatic ultrastructure, including collagen deposition in the space of Disse and changes in hepatocyte lysosomes.